1
|
Li Y, Li Y, Tang B, Yue Q, Luo B, Zhu M. An EEG-based analysis of the effects of different music genres on driving stress. Front Hum Neurosci 2025; 19:1560920. [PMID: 40177163 PMCID: PMC11961950 DOI: 10.3389/fnhum.2025.1560920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 03/05/2025] [Indexed: 04/05/2025] Open
Abstract
Introduction Sudden road conditions can trigger drivers' psychological stress, increasing the risk of traffic accidents. Music, as an emotion regulation tool, effectively alleviates stress and enhances psychological health. However, the effects of different genres of music on drivers' stress remain understudied. Methods To address this, the present study collected 120 EEG recordings from 60 drivers in a standardized simulated driving environment and developed a classification model based on EEG signals to recognize emotions. By integrating time-frequency domain features (mean, variance, skewness, kurtosis, and power spectral density) with classification algorithms, the model accurately identified slight, moderate, and severe stress states in drivers, achieving an accuracy of 90%. Results Furthermore, the study evaluated the intervention effects of four types of music (joyful, sorrowful, exhilarating, and gentle) on stress using EEG signals and subjective stress ratings. The results showed that gentle music had the best stress-relieving effect in both slight and severe stress states, reducing stress by 41.67% and 45%, respectively, whereas joyful music was most effective in relieving moderate stress, reducing moderate stress by 50%. In contrast, exhilarating and sorrowful music had weaker effects. Additionally, the asymmetry of frontal pole EEG signals was found to be significantly negatively correlated with stress levels. Discussion This finding further supports the accuracy of the emotion recognition model and the potential effectiveness of the music intervention strategy. The study demonstrates that personalized music intervention strategies can help alleviate drivers' stress, thereby improving psychological health, enhancing driving safety, and increasing driving comfort.
Collapse
Affiliation(s)
- Yilun Li
- School of Music and Dance, Henan Institute of Science and Technology, Xinxiang, China
| | - Yan Li
- School of Intelligent Manufacturing Engineering, Chongqing University of Arts and Sciences, Chongqing, China
| | - Bangbei Tang
- School of Intelligent Manufacturing Engineering, Chongqing University of Arts and Sciences, Chongqing, China
- Department of Physiology, Army Medical University, Chongqing, China
| | - Qizong Yue
- School of Music, Southwest University, Chongqing, China
| | - Bingjie Luo
- School of Intelligent Manufacturing Engineering, Chongqing University of Arts and Sciences, Chongqing, China
| | - Mingxin Zhu
- School of Mechanical Engineering, Sichuan University of Science and Engineering, Yibin, China
| |
Collapse
|
2
|
Atchade A, Yadouleton A, Fiogbe M, Abdoulaye Alfa D, Yovo E, Le Hesran JY, Hounsa S, Bationo C, Figueroa-Romero A, Gaudart J, González R, Bonnet E, Massougbodji A, Cottrell G. Determinants of SARS-CoV-2 infection across three sentinels sites in Benin during 2021: A multicentric surveillance study. PLOS GLOBAL PUBLIC HEALTH 2025; 5:e0004227. [PMID: 39946403 PMCID: PMC11824965 DOI: 10.1371/journal.pgph.0004227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 01/10/2025] [Indexed: 02/16/2025]
Abstract
TRIAL REGISTRATION NCT06170320 (retrospectively registered on December 21, 2023).
Collapse
Affiliation(s)
- Aurore Atchade
- Institut de Recherche Clinique du Bénin - IRCB, Abomey-Calavi, Bénin
| | - Anges Yadouleton
- Ministère de la Santé du Bénin, Laboratoire des Fièvres Hémorragiques Virales du Bénin, Cotonou, Bénin
| | - Marc Fiogbe
- Institut de Recherche Clinique du Bénin - IRCB, Abomey-Calavi, Bénin
| | | | - Emmanuel Yovo
- Institut de Recherche Clinique du Bénin - IRCB, Abomey-Calavi, Bénin
| | | | - Sandrine Hounsa
- Institut de Recherche Clinique du Bénin - IRCB, Abomey-Calavi, Bénin
| | - Cédric Bationo
- Aix Marseille Univ, IRD, INSERM, SESSTIM, ISSPAM, UMR1252, APHM, Hop Timone, BioSTIC, Biostatistic and ICT, Marseille, France
| | - Antía Figueroa-Romero
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic- Universitat de Barcelona, Barcelona, Spain
| | - Jean Gaudart
- Aix Marseille Univ, IRD, INSERM, SESSTIM, ISSPAM, UMR1252, APHM, Hop Timone, BioSTIC, Biostatistic and ICT, Marseille, France
| | - Raquel González
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic- Universitat de Barcelona, Barcelona, Spain
- Manhiça Health Research Center (CISM), Manhica, Mozambique
| | - Emmanuel Bonnet
- Université Paris 1 Panthéon-Sorbonne, IRD PRODIG UMR 215, CNRS AgroParisTech 5, cours des Humanités, Aubervilliers, France
| | | | | |
Collapse
|
3
|
Justiz-Vaillant A, Soodeen S, Gopaul D, Arozarena-Fundora R, Thompson R, Unakal C, Akpaka PE. Tackling Infectious Diseases in the Caribbean and South America: Epidemiological Insights, Antibiotic Resistance, Associated Infectious Diseases in Immunological Disorders, Global Infection Response, and Experimental Anti-Idiotypic Vaccine Candidates Against Microorganisms of Public Health Importance. Microorganisms 2025; 13:282. [PMID: 40005649 PMCID: PMC11858333 DOI: 10.3390/microorganisms13020282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/14/2025] [Accepted: 01/15/2025] [Indexed: 02/27/2025] Open
Abstract
This paper explores various aspects of microbiology and immunology, with a particular focus on the epidemiology and molecular characterisation of infectious diseases in the Caribbean and South America. Key areas of investigation include tuberculosis (TB), experimental vaccines, and bloodborne pathogens. A retrospective study conducted in Jamaica highlights the significance of early HIV screening, timely diagnosis, and inte-grated care. The paper also examines the challenges posed by nosocomial infections, particularly those caused by antibiotic-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), emphasising the critical importance of infection control measures. Additionally, it explores the regional microbiome, the global response to infectious diseases, and immune responses in patients with immunodeficiency disorders such as severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD), underscoring their heightened susceptibility to a wide range of infections.
Collapse
Affiliation(s)
- Angel Justiz-Vaillant
- Department of Para-Clinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine 330912, Trinidad and Tobago; (S.S.); (R.T.); (C.U.); (P.E.A.)
| | - Sachin Soodeen
- Department of Para-Clinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine 330912, Trinidad and Tobago; (S.S.); (R.T.); (C.U.); (P.E.A.)
| | - Darren Gopaul
- Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA;
| | - Rodolfo Arozarena-Fundora
- Eric Williams Medical Sciences Complex, North Central Regional Health Authority, Champs Fleurs 330912, Trinidad and Tobago;
- Department of Clinical and Surgical Sciences, Faculty of Medical Sciences, The University of the West Indies, St. Augustine 330912, Trinidad and Tobago
| | - Reinand Thompson
- Department of Para-Clinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine 330912, Trinidad and Tobago; (S.S.); (R.T.); (C.U.); (P.E.A.)
| | - Chandrashekhar Unakal
- Department of Para-Clinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine 330912, Trinidad and Tobago; (S.S.); (R.T.); (C.U.); (P.E.A.)
| | - Patrick E. Akpaka
- Department of Para-Clinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine 330912, Trinidad and Tobago; (S.S.); (R.T.); (C.U.); (P.E.A.)
- Eric Williams Medical Sciences Complex, North Central Regional Health Authority, Champs Fleurs 330912, Trinidad and Tobago;
| |
Collapse
|
4
|
Cavalcante FV, Martin CPS, Frio GS, Stabeli RG, Santos LMP. Laboratory readiness and genomic surveillance of Covid-19 in the capital of Brazil. PLOS GLOBAL PUBLIC HEALTH 2025; 5:e0003289. [PMID: 39787152 PMCID: PMC11717220 DOI: 10.1371/journal.pgph.0003289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 11/14/2024] [Indexed: 01/12/2025]
Abstract
This study aims to analyze the diagnostic readiness to Covid-19 and the genomic surveillance of SARS-CoV-2 in Brasília, the capital of Brazil. This is a retrospective, cross-sectional study, with data from: cases/deaths-Ministry of Health; RT-PCR analyses Brasília Central Public Health Laboratory (LACEN); genomics-Global Initiative on Sharing All Influenza Data (GISAID). It was found that in March 2021, with the Gamma variant was predominant, RT-PCR diagnostic tests administered by LACEN reached their peak, followed by a reduction, possibly due to the start of vaccination. New peaks were observed in September 2021 and January 2022. The average time for releasing RT-PCR results was reduced from eight days (July 2020), to around eight hours in 2023. The participation of private laboratories was evident in sequencing the SARS-CoV-2 variants of concern in Brasília (n = 1,897). LACEN sequenced 50% of the samples received (571). A decrease in the incidence of cases and deaths due to Covid-19 was noted in the years 2022 to 2023, following the national trend. LACEN maintained RT-PCR diagnostic tests administered satisfactorily throughout the period. Regarding the genomic surveillance of SARS-CoV-2, the vast majority of samples were sequenced by private laboratories when compared to the public laboratory.
Collapse
Affiliation(s)
| | | | - Gustavo Saraiva Frio
- Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brasil
| | | | | |
Collapse
|
5
|
Mukhopadhyay H, Bairagi A, Mukherjee A, Prasad AK, Roy AD, Nayak A. Multidrug resistant Acinetobacter baumannii: A study on its pathogenesis and therapeutics. CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 8:100331. [PMID: 39802320 PMCID: PMC11718326 DOI: 10.1016/j.crmicr.2024.100331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025] Open
Abstract
The overuse of antibiotics has led to the global dissemination of Acinetobacter baumannii, an increasingly challenging nosocomial pathogen. This review explores the medical significance along with the diverse resistance ability of A. baumannii. Intensive care units (ICUs) serve as a breeding ground for A. baumannii, as these settings harbour vulnerable patients and facilitate the spread of opportunistic microorganisms. A. baumannii belongs to the ESKAPE group of bacterial pathogens that are major contributors to antibiotic-resistant infections. The pathogenic nature of A. baumannii is particularly evident in seriously ill patients, causing pneumonia, wound infections, and other healthcare-associated infections. Historically considered benign, A. baumannii is a global threat due to its propensity for rapid acquisition of multidrug resistance phenotypes. The genus Acinetobacter was formally recognized in 1968 following a comprehensive survey by Baumann et al., highlighting the relationship between previously identified species and consolidating them under the name Acinetobacter. A. baumannii is characterized by its Gram-negative nature, dependence on oxygen, positive catalase activity, lack of oxidase activity, inability to ferment sugars, and non-motility. The DNA G+C content of Acinetobacter species falls within a specific range. For diagnostic purposes, A. baumannii can be cultured on specific agar media, producing distinct colonies. The genus Acinetobacter comprises numerous species those are associated with bloodstream infections with high mortality rates. Therefore, A. baumannii poses a significant challenge to global healthcare due to its multidrug resistance and ability to cause various infections. A comprehensive understanding of the mechanisms underlying its resistance acquisition and pathogenicity is essential for combating this healthcare-associated pathogen effectively.
Collapse
Affiliation(s)
- Hridesh Mukhopadhyay
- Department of Microbiology, Ramakrishna Mission Vivekananda Centenary College, Rahara, Khardaha, West Bengal 700118, India
| | - Arnab Bairagi
- Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala 695014, India
| | - Anushka Mukherjee
- Maulana Abul Kalam Azad University of Technology, West Bengal, India
| | | | - Arjama Dhar Roy
- Serampore Vivekananda Academy, Serampore, Hooghly 712203, West Bengal, India
| | - Aditi Nayak
- Department of Life Science, Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| |
Collapse
|
6
|
Doğan U, Karataş G, İlter SM. Factors Affecting Procedural Pain and Discomfort Experienced by Individuals During Nasopharyngeal Swabbing: A Cross-Sectional Study. FLORENCE NIGHTINGALE JOURNAL OF NURSING 2024; 32:215-220. [PMID: 39530582 PMCID: PMC11562252 DOI: 10.5152/fnjn.2024.22289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 07/09/2024] [Indexed: 11/16/2024]
Abstract
Aim This descriptive and cross-sectional study investigated the individual factors that affect procedural pain and discomfort in individuals who had nasopharyngeal swabs by nurses. Methods A total of 193 participants in two COVID-19 test centers located in a city in Southeastern Türkiye between April and May 2022 were included in this study. Personal information form was used to collect data. The visual analog scale was used to assess the pain and discomfort. Risk factors related to pain and discomfort were investigated through a logistic regression model. Results During the nasopharyngeal swabbing, it was determined that pain was stronger in women and those who considered nasopharyngeal swabbing as a painful procedure (p < .05). Also, discomfort was stronger in women and those who considered nasopharyngeal swabbing as an uncomfortable procedure (p < .05). It was determined that the participants' discomfort scores were higher than their pain scores. Conclusion Women and individuals with negative opinions about the procedure experienced more pain and discomfort during the nasopharyngeal swabbing. Most of the participants complained more about discomfort than pain. It is recommended to apply alternate test methods and conduct nurse-led information studies to reduce the anticipation of procedural pain/discomfort.
Collapse
Affiliation(s)
- Uğur Doğan
- Department of Nursing, Kilis 7 Aralık University, Kilis, Türkiye
| | - Gülsen Karataş
- Department of First Aid and Emergency, Kilis 7 Aralık University, Kilis, Türkiye
| | | |
Collapse
|
7
|
Nakamoto T, Iwamoto N, Oshiro Y, Inamura N, Nemoto T, Ide S, Nakamura K, Nomoto H, Akiyama Y, Suzuki T, Miyazato Y, Suzuki M, Suzuki K, Kimura M, Saito S, Kutsuna S, Ohmagari N. COVID-19 severity and corticosteroid treatment have minimal effect on specific antibody production. BMC Infect Dis 2024; 24:1197. [PMID: 39443853 PMCID: PMC11515524 DOI: 10.1186/s12879-024-10090-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 10/15/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment. METHODS Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment. RESULTS Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6-10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment. CONCLUSIONS In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity.
Collapse
Affiliation(s)
- Takato Nakamoto
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan.
| | - Noriko Iwamoto
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Yusuke Oshiro
- Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan
| | - Natsumi Inamura
- Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan
| | - Takashi Nemoto
- Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan
| | - Satohi Ide
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Keiji Nakamura
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
- Center for the Study fo Global IInfection, Kushu University Hospital, Fukuoka, Japan
| | - Hidetoshi Nomoto
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Yutaro Akiyama
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Tetsuya Suzuki
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Yusuke Miyazato
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Michiyo Suzuki
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Kumiko Suzuki
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan
| | - Moto Kimura
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Tokyo, 162-8655, Japan
| | - Sho Saito
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Satoshi Kutsuna
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
- Department of Infection Control, Graduate School of Medicine / Faculty of Medicine, Osaka University, Suita City, Osaka, 565-0871, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center/Travel Clinic, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| |
Collapse
|
8
|
Cavalcanti-Dantas VDM, da Silva AF, Mendes AF, de Araújo Júnior WO, Bernardo-Menezes LC, Bresani-Salvi CC, Castellano LRC, Fernandes AIV, Lemos SG, de Magalhães JJF, Oliveira RADS, de Assis PAC, de Souza JR, de Morais CNL. Performance assessment of a new serological diagnostic test for COVID-19 with candidate peptides from spike and nucleocapsid viral proteins. Braz J Microbiol 2024; 55:2797-2803. [PMID: 39042245 PMCID: PMC11405565 DOI: 10.1007/s42770-024-01446-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 06/28/2024] [Indexed: 07/24/2024] Open
Abstract
Numerous commercial tests for the serological diagnosis of COVID-19 have been produced in recent years. However, it is important to note that these tests exhibit significant variability in their sensitivity, specificity, and accuracy of results. Therefore, the objective of this study was to utilize bioinformatics tools to map SARS-CoV-2 peptides, with the goal of developing a new serological diagnostic test for COVID-19. Two peptides from the S protein and one from the N protein were selected and characterized in silico, chemically synthesized, and used as a serological diagnostic tool to detect IgM, IgG, and IgA anti-SARS-CoV-2 antibodies through the ELISA technique, confirmed as positive and negative samples by RT-qPCR or serology by ELISA. The results showed a sensitivity, specificity, Positive Predictive Value and Negative Predictive Value of 100% (p < 00001, 95% CI) for the proposed test. Although preliminary, this study brings proof-of-concept results that are consistent with the high-performance rates of the ELISA test when compared to other well-established methods for diagnosing COVID-19.
Collapse
Affiliation(s)
- Vanessa de Melo Cavalcanti-Dantas
- Laboratory of Virology and Experimental Therapy, Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil
| | - Alan Frazão da Silva
- Laboratory of Experimental Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Andrei Félix Mendes
- Laboratory of Microbiology, Department of Microbiology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil
| | - Waldecir Oliveira de Araújo Júnior
- Laboratory of Immunology and Hematology, Department of Physiology and Pathology, Multidisciplinary Research Group in Biotechnology and Health (GePeMBiS), Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Lucas Coêlho Bernardo-Menezes
- Laboratory of Virology and Experimental Therapy, Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil
| | - Cristiane Campello Bresani-Salvi
- Laboratory of Virology and Experimental Therapy, Department of Virology, Group of Integrated Studies in Nutrition and Health, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Instituto de Medicina Integral Prof Fernando Figueira, Recife, Pernambuco, Brazil
| | - Lúcio Roberto Cançado Castellano
- Professional and Technological Center of the Technical School of Health, Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Ana Isabel Vieira Fernandes
- Health Promotion Department of the Medical Sciences Center and Division for Infectious and Parasitic Diseases, Lauro Wanderley University Hospital, Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Sherlan Guimarães Lemos
- Advanced Study Group in Analytical Chemistry, Department of Chemistry, Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Jurandy Júnior Ferraz de Magalhães
- Laboratory of Virology and Experimental Therapy, Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil
| | - Renato Antônio Dos Santos Oliveira
- Laboratory of Immunology and Hematology, Department of Physiology and Pathology, Multidisciplinary Research Group in Biotechnology and Health (GePeMBiS), Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Priscilla Anne Castro de Assis
- Laboratory of Immunology and Hematology, Department of Physiology and Pathology, Multidisciplinary Research Group in Biotechnology and Health (GePeMBiS), Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Joelma Rodrigues de Souza
- Laboratory of Immunology and Hematology, Department of Physiology and Pathology, Multidisciplinary Research Group in Biotechnology and Health (GePeMBiS), Federal University of Paraiba, João Pessoa, Paraíba, Brazil
| | - Clarice Neuenschwander Lins de Morais
- Laboratory of Virology and Experimental Therapy, Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Pernambuco, Brazil.
| |
Collapse
|
9
|
Ding H, Fan L, Zhang J, Gao G. Deep Learning-Based System Combining Chest X-Ray and Computerized Tomography Images for COVID-19 Diagnosis. Br J Hosp Med (Lond) 2024; 85:1-15. [PMID: 39212565 DOI: 10.12968/hmed.2024.0244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Aims/Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for accurate and efficient diagnostic methods. This study aims to improve COVID-19 detection by integrating chest X-ray (CXR) and computerized tomography (CT) images using deep learning techniques, further improving diagnostic accuracy by using a combined imaging approach. Methods: The study used two publicly accessible databases, COVID-19 Questionnaires for Understanding the Exposure (COVID-QU-Ex) and Integrated Clinical and Translational Cancer Foundation (iCTCF), containing CXR and CT images, respectively. The proposed system employed convolutional neural networks (CNNs) for classification, specifically EfficientNet and ResNet architectures. The data underwent preprocessing steps, including image resizing, Gaussian noise addition, and data augmentation. The dataset was divided into training, validation, and test sets. Gradient-weighted Class Activation Mapping (Grad-CAM) was used for model interpretability. Results: The EfficientNet-based models outperformed the ResNet-based models across all metrics. The highest accuracy achieved was 99.44% for CXR images and 99.81% for CT images with EfficientNetB5. The models also demonstrated high precision, recall, and F1 scores. For statistical significance, the p-values were less than 0.05, indicating that the results are significant. Conclusion: Integrating CXR and CT images using deep learning significantly improves the accuracy of COVID-19 diagnosis. The EfficientNet-based models, with their superior feature extraction capabilities, show better performance than ResNet models. Grad-CAM Visualizations provide insights into the model's decision-making process, potentially reducing diagnostic errors and accelerating diagnosis processes. This approach can improve patient care and support healthcare systems in managing the pandemic more effectively.
Collapse
Affiliation(s)
- Hui Ding
- Department of Radiology, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Lingyan Fan
- Department of Acute Infectious Diseases, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Jingfeng Zhang
- Department of Radiology, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Guosheng Gao
- Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| |
Collapse
|
10
|
Neofytos D, Khanna N. How I treat: Coronavirus disease 2019 in leukemic patients and hematopoietic cell transplant recipients. Transpl Infect Dis 2024; 26:e14332. [PMID: 38967400 DOI: 10.1111/tid.14332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/14/2024] [Accepted: 06/21/2024] [Indexed: 07/06/2024]
Abstract
Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID-19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID-19 require careful consideration of factors such as COVID-19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non-viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID-19 in leukemia patients.
Collapse
Affiliation(s)
- Dionysios Neofytos
- Division of Infectious Diseases, Transplant Unit, University Hospitals of Geneva, Geneva, Switzerland
| | - Nina Khanna
- Departments of Biomedicine and Clinical Research, Division of Infectious Diseases, University and University Hospital of Basel, Basel, Switzerland
| |
Collapse
|
11
|
Castro NC, Bullock J, Haynesworth K, Loftus S, Metz J, North H, Kemp TJ, Pinto LA. Blood collection tube and anticoagulant influence on SARS-CoV-2 antibody and avidity levels. Heliyon 2024; 10:e34449. [PMID: 39114031 PMCID: PMC11305197 DOI: 10.1016/j.heliyon.2024.e34449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 07/09/2024] [Accepted: 07/09/2024] [Indexed: 08/10/2024] Open
Abstract
SARS-CoV-2 serology plays a crucial role in assessing COVID-19 vaccine immunogenicity and antibody responses to SARS-CoV-2 infection. Tube type and anticoagulant may influence serology results. Thus, understanding the influence of these variables in test results is key. We evaluated the influence of serum collection tube type and anticoagulant on anti-SARS-CoV-2 spike antibody levels detected by enzyme-linked immunosorbent assays (ELISAs) and Luminex multiplex assays (11-plex) in serum and plasma samples. Anti-spike IgG avidity was also evaluated in both sample types. No significant differences were found between serology assay results using different blood (serum) collection tube types. However, significantly lower antibody concentrations (p < 0.05) were observed in tubes with the anticoagulants sodium citrate and acid citrate dextrose (ACD) in the ELISA and Multiplex assays (n = 29), compared to expected concentrations. These differences mostly disappeared after adjusting for the dilution factor caused by the anticoagulant volume, indicating that anticoagulant does not significantly impact the assay results, while anticoagulant volume does. There was a significant difference (p < 0.05) in IgG avidity (M) of plasma samples (p < 0.05) compared to serum, but anticoagulant type had no effect. Overall, these findings indicate that the choice of collection tube may introduce subtle variations in assay results if the volumes of anticoagulants are not taken into consideration. Additionally, differences between serum and anticoagulant-treated plasma matrices were observed in avidity ELISAs, indicating that these samples are not interchangeable for these assays; a finding that requires further investigation.
Collapse
Affiliation(s)
- Nicholas C. Castro
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Jimmie Bullock
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Katarzyna Haynesworth
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Sarah Loftus
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Jordan Metz
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Hayley North
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Troy J. Kemp
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| | - Ligia A. Pinto
- Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA
| |
Collapse
|
12
|
Shire FM, Sharbatti S, AlNajjar F, Sulaiman Abumuaileq L, Abuelkher R, Sabri H, Beevi A, Alqahtani A, Beshtawy R. The Impact of Viral Load on the Severity and Outcome Among Patients With COVID-19: A Cross-Sectional Study. Cureus 2024; 16:e64137. [PMID: 39119409 PMCID: PMC11307488 DOI: 10.7759/cureus.64137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/09/2024] [Indexed: 08/10/2024] Open
Abstract
Objectives This study aimed to assess the relationship between illness severity and mortality among COVID-19 patients along with the cycle threshold (Ct) value measured by viral load. Methods A cross-sectional study was conducted based on records of the emergency room at Rashid Hospital located in Dubai, United Arab Emirates. This research was carried out on all of the appropriate records of patients who were hospitalized at Rashid Hospital in Dubai between May 2020 and January 2021. Clinical and laboratory data were used as severity indicators, and in-hospital death was designated as the outcome. Results A total of 1,633 cases were included in the analysis. The percentage of deceased patients was higher in patients with a low Ct value (11.6%) than in patients with a high Ct value (6.9%) (p-value = 0.003). Logistic analysis revealed a statistically significant correlation (OR=2.046; p-value=0.002) between mortality and viral load, as measured by the Ct value. Patients with low Ct values and aberrant laboratory findings had a higher frequency of respiratory problems and required oxygen therapy, according to clinical and laboratory markers. Conclusions A correlation was found between viral load and mortality. Advanced age, history of chronic disease, and abnormal clinical and laboratory findings were all independently linked to a greater mortality rate in COVID-19 patients, indicating that they might be utilized as predictive and prognostic factors along with the viral load.
Collapse
Affiliation(s)
- Fatma M Shire
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| | - Shatha Sharbatti
- Community Medicine Department, Gulf Medical University, Ajman, ARE
| | - Firas AlNajjar
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| | | | - Rand Abuelkher
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| | - Hebah Sabri
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| | - Aasiya Beevi
- Medical Education Department, Dubai Medical College for Girls, Dubai, ARE
| | - Alia Alqahtani
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| | - Rami Beshtawy
- Emergency Department, Rashid Hospital, Dubai Academic Health Corporation, Dubai, ARE
| |
Collapse
|
13
|
Alharbi AS, Al-Hindi MY, Alqwaiee M, Al-Shamrani A, Alharbi S, Yousef A, Alshammary A, Miqdad A, Said Y, Alnemri A, Alahmadi T, Almudeer AH. Saudi Initiative of Bronchiolitis Diagnosis, Management, and Prevention 2024 updated consensus on the prevention of respiratory syncytial virus. Ann Thorac Med 2024; 19:190-200. [PMID: 39144535 PMCID: PMC11321529 DOI: 10.4103/atm.atm_69_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 04/07/2024] [Indexed: 08/16/2024] Open
Abstract
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis among children under 5 years of age worldwide, accounting for a prevalence of 25%-88% in Saudi Arabia. Although no effective treatment for the virus exists, passive immunoprophylaxis reduced RSV hospitalizations in high-risk children. With recent advances in immunization, the Saudi Initiative of Bronchiolitis Diagnosis, Management, and Prevention panel screened recent relevant international guidelines, locally published data, and expert consensus to update guidelines for RSV prevention, taking into consideration the resources, timing, varying health profiles, and RSV burden in Saudi Arabia. The panel updated its recommendations to include immunization of infants, mothers, and older adults. Practical guidelines were prepared to facilitate the administration of the short-acting and newly developed long-acting RSV monoclonal antibodies (mAb) during the regular follow-ups of high-risk infants in specialized clinics. In addition, long-acting mAb was highlighted as all-infant protection in the routine immunization calendar.
Collapse
Affiliation(s)
- Adel S. Alharbi
- Department of Pediatrics, Prince Sultan Military City, Ministry of Defense, Riyadh, Saudi Arabia
| | - Mohammed Y Al-Hindi
- Department of Pediatric, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
- Research and Development, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
- Department of Pediatrics, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mansour Alqwaiee
- Department of Pediatrics, Prince Sultan Military City, Ministry of Defense, Riyadh, Saudi Arabia
| | - Abdullah Al-Shamrani
- Department of Pediatrics, Prince Sultan Military City, Ministry of Defense, Riyadh, Saudi Arabia
| | - Saleh Alharbi
- Department of Pediatrics, Umm Al Qura University, Makkah, Saudi Arabia
| | - Abdullah Yousef
- Department of Pediatrics, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Aisha Alshammary
- Department of Pediatrics, Alyammamah Hospital, Ministry of Health, Riyadh, Saudi Arabia
| | - Abeer Miqdad
- Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia
| | - Yazan Said
- Department of Pediatrics, King Fahad Specialist Hospital, Ministry of Health, Dammam, Saudi Arabia
| | - Abdulrahman Alnemri
- Department of Pediatrics, College of Medicine, Pediatrics Department, King Saud University, Riyadh, Saudi Arabia
| | - Turki Alahmadi
- Department of Pediatrics, College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ali Husein Almudeer
- Department of Pediatrics, College of Medicine, Pediatrics Department, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
14
|
Oliveira CVDS, Pepe VLE. Health policy and regulatory authorities: challenges of technology regulation in Public Health Emergencies. CIENCIA & SAUDE COLETIVA 2024; 29:e03442024. [PMID: 38958323 DOI: 10.1590/1413-81232024297.03442024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 02/01/2024] [Indexed: 07/04/2024] Open
Abstract
Public Health Emergencies (PHE) have had repercussions on health systems on a global scale, and timely access to new health technologies is a challenge for health policy. The national regulatory authorities (NRA) play a key role in the evaluation and regulation of these technologies. The present study aims to analyze the main strategies and regulatory instruments used to deal with the challenges of regulating new technologies necessary for the health system's effective response during a PHE. This research, based on WHO and Brazilian NRA norms and documents, considered dimensions related to strategies for strengthening regulatory activities and regulatory instruments used to accelerate access to technologies, especially during PHEs. International cooperation between the NRA and the WHO were important strategies for strengthening the NRA, with emphasis on the use of reliance, regionalization, accelerated assessments, and work/information sharing, as well as the processes of regulatory harmonization and convergence. In addition to the use of existing regulatory instruments, efforts were also identified in order to implement new ones.
Collapse
Affiliation(s)
- Catia Veronica Dos Santos Oliveira
- Programa de Pós-Graduação em Saúde Pública, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. R. Leopoldo Bulhões 1480, Manguinhos. 21041-210 Rio de Janeiro RJ Brasil.
- Departamento de Administração e Planejamento em Saúde, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. Rio de Janeiro RJ Brasil
| | - Vera Lúcia Edais Pepe
- Programa de Pós-Graduação em Saúde Pública, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. R. Leopoldo Bulhões 1480, Manguinhos. 21041-210 Rio de Janeiro RJ Brasil.
- Departamento de Administração e Planejamento em Saúde, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz. Rio de Janeiro RJ Brasil
| |
Collapse
|
15
|
Imai H, Suzuki J, Takahashi S, Shimada D, Yoshida M, Endo S, Kaku M. The Epidemiology of Circulating Respiratory Pathogens during the COVID-19 Pandemic. Intern Med 2024; 63:1683-1687. [PMID: 38494719 PMCID: PMC11239251 DOI: 10.2169/internalmedicine.3266-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/19/2024] Open
Abstract
Objective To survey the epidemiology of respiratory pathogens during the coronavirus disease 2019 (COVID-19) pandemic using multiplex polymerase chain reaction (PCR). Methods Specimens were assayed using multiplex nested PCR. Materials Specimens were obtained from outpatients who presented with symptoms of upper respiratory tract infection and asymptomatic outpatients who had contact with patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Tohoku Medical and Pharmaceutical University Hospital in Sendai, Japan, from November 1, 2020, to May 31, 2023. The analysis included multiple specimens collected from the same patients at different time-points. Data were collected from the electronic records after testing. Results This study included 8,335 patients (4,311 men) with a median age of 59 years old, and 11,741 total specimens were collected. At least 1 positive SARS-CoV-2 result was obtained for 1,710 (14.6%) specimens. Furthermore, 15 pathogens were identified in the positive specimens, and rhinovirus/enterovirus was detected more frequently than other viruses. We identified a larger number of SARS-CoV-2-positive specimens in patients ≥10 years old. In contrast, in patients 0-9 years old, we identified a larger number of specimens positive for rhinovirus/enterovirus than for other viruses. Conclusion In this study, we examined the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic era.
Collapse
Affiliation(s)
- Haruka Imai
- Division of Infectious Diseases, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Department of Infection Prevention and Control, Tohoku Medical and Pharmaceutical University Hospital, Japan
| | - Jun Suzuki
- Division of Infectious Diseases, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Department of Infection Prevention and Control, Tohoku Medical and Pharmaceutical University Hospital, Japan
| | - Shota Takahashi
- Department of Infection Prevention and Control, Tohoku Medical and Pharmaceutical University Hospital, Japan
| | - Daishi Shimada
- Division of Infectious Diseases, Tohoku Medical and Pharmaceutical University Hospital, Japan
| | - Makiko Yoshida
- Division of Crisis Management Network for Infectious Diseases, Tohoku Medical and Pharmaceutical University, Japan
| | - Shiro Endo
- Division of Infectious Diseases, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Department of Infection Prevention and Control, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Division of Crisis Management Network for Infectious Diseases, Tohoku Medical and Pharmaceutical University, Japan
| | - Mitsuo Kaku
- Division of Infectious Diseases, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Department of Infection Prevention and Control, Tohoku Medical and Pharmaceutical University Hospital, Japan
- Division of Crisis Management Network for Infectious Diseases, Tohoku Medical and Pharmaceutical University, Japan
| |
Collapse
|
16
|
Petros BA, Milliren CE, Sabeti PC, Ozonoff A. Increased Pediatric Respiratory Syncytial Virus Case Counts Following the Emergence of SARS-CoV-2 Can Be Attributed to Changes in Testing. Clin Infect Dis 2024; 78:1707-1717. [PMID: 38602423 PMCID: PMC11175668 DOI: 10.1093/cid/ciae140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naїve pediatric population increased during the period of low transmission. However, the evidence supporting this hypothesis is limited, and the role of changing testing practices in the perceived surge has not been comprehensively evaluated. METHODS We conducted a multicenter, retrospective analysis of 342 530 RSV encounters and 980 546 RSV diagnostic tests occurring at 32 US pediatric hospitals in 2013-2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and test volume and to quantify changes in the proportions of patients requiring hospitalization, intensive care, or mechanical ventilation. We quantified the fraction of the shifts in case counts and in the age of diagnosed patients attributable to changes in testing. RESULTS RSV patient volume increased 2.4-fold (95% confidence interval [CI]: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Shifts in patient volume and in patient age were largely attributable to increased testing. The proportions of patients with RSV that required hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. CONCLUSIONS A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. These findings warrant a critical assessment of the immunity debt hypothesis and highlight the importance of considering the testing denominator when surveillance strategies are dynamic.
Collapse
Affiliation(s)
- Brittany A Petros
- Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
- Health Sciences & Technology Program, Harvard Medical School and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- Harvard–Massachusetts Institute of Technology MD-PhD Program, Boston, Massachusetts, USA
- Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
| | - Carly E Milliren
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Pardis C Sabeti
- Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA
- Department of Immunology & Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
- Howard Hughes Medical Institute, Chevy Chase, Maryland, USA
| | - Al Ozonoff
- Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
- Precision Vaccines Program, Boston Children's Hospital, Boston, Massachusetts, USA
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
17
|
Lin J, Aprahamian H, Golovko G. An optimization framework for large-scale screening under limited testing capacity with application to COVID-19. Health Care Manag Sci 2024; 27:223-238. [PMID: 38656689 DOI: 10.1007/s10729-024-09671-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 02/27/2024] [Indexed: 04/26/2024]
Abstract
We consider the problem of targeted mass screening of heterogeneous populations under limited testing capacity. Mass screening is an essential tool that arises in various settings, e.g., ensuring a safe supply of blood, reducing prevalence of sexually transmitted diseases, and mitigating the spread of infectious disease outbreaks. The goal of mass screening is to classify whole population groups as positive or negative for an infectious disease as efficiently and accurately as possible. Under limited testing capacity, it is not possible to screen the entire population and hence administrators must reserve testing and target those among the population that are most in need or most susceptible. This paper addresses this decision problem by taking advantage of accessible population-level risk information to identify the optimal set of sub-populations to target for screening. We conduct a comprehensive analysis that considers the two most commonly adopted schemes: Individual testing and Dorfman group testing. For both schemes, we formulate an optimization model that aims to minimize the number of misclassifications under a testing capacity constraint. By analyzing the formulations, we establish key structural properties which we use to construct efficient and accurate solution techniques. We conduct a case study on COVID-19 in the United States using geographic-based data. Our results reveal that the considered proactive targeted schemes outperform commonly adopted practices by substantially reducing misclassifications. Our case study provides important managerial insights with regards to optimal allocation of tests, testing designs, and protocols that dictate the optimality of schemes. Such insights can inform policy-makers with tailored and implementable data-driven recommendations.
Collapse
Affiliation(s)
- Jiayi Lin
- Department of Industrial and Systems Engineering, Texas A &M University, College Station, 77843, TX, USA.
| | - Hrayer Aprahamian
- Department of Industrial and Systems Engineering, Texas A &M University, College Station, 77843, TX, USA
| | - George Golovko
- Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, 77555, TX, USA
| |
Collapse
|
18
|
Lintala A, Vapalahti O, Nousiainen A, Kantele A, Hepojoki J. Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay-Förster Resonance Energy Transfer-Based Antibody Detection. Diagnostics (Basel) 2024; 14:720. [PMID: 38611633 PMCID: PMC11011549 DOI: 10.3390/diagnostics14070720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/22/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
The protein-L-utilizing Förster resonance energy transfer (LFRET) assay enables mix-and-read antibody detection, as demonstrated for sera from patients with, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and orthohantavirus infections. In this study, we compared paired serum and whole blood (WB) samples of COVID-19 patients and SARS-CoV-2 vaccine recipients. We found that LFRET also detects specific antibodies in WB samples. In 44 serum-WB pairs from patients with laboratory-confirmed COVID-19, LFRET showed a strong correlation between the sample materials. By analyzing 89 additional WB samples, totaling 133 WB samples, we found that LFRET results were moderately correlated with enzyme-linked immunosorbent assay results for samples collected 2 to 14 months after receiving COVID-19 diagnosis. However, the correlation decreased for samples >14 months after receiving a diagnosis. When comparing the WB LFRET results to neutralizing antibody titers, a strong correlation emerged for samples collected 1 to 14 months after receiving a diagnosis. This study also highlights the versatility of LFRET in detecting antibodies directly from WB samples and suggests that it could be employed for rapidly assessing antibody responses to infectious agents or vaccines.
Collapse
Affiliation(s)
- Annika Lintala
- Department of Virology, Faculty of Medicine, Medicum, University of Helsinki, 00290 Helsinki, Finland
| | - Olli Vapalahti
- Department of Virology, Faculty of Medicine, Medicum, University of Helsinki, 00290 Helsinki, Finland
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland
- Helsinki University Hospital Diagnostic Center, 00029 Helsinki, Finland
| | - Arttu Nousiainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Meilahti Infectious Diseases and Vaccine Research Center, MeiVac, Department of Infectious Diseases, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
| | - Anu Kantele
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Meilahti Infectious Diseases and Vaccine Research Center, MeiVac, Department of Infectious Diseases, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
| | - Jussi Hepojoki
- Department of Virology, Faculty of Medicine, Medicum, University of Helsinki, 00290 Helsinki, Finland
- Vetsuisse Faculty, Institute of Veterinary Pathology, University of Zürich, 8057 Zürich, Switzerland
| |
Collapse
|
19
|
Alsayed AR, Ahmed SI, AL Shweiki AO, Al-Shajlawi M, Hakooz N. The laboratory parameters in predicting the severity and death of COVID-19 patients: Future pandemic readiness strategies. BIOMOLECULES & BIOMEDICINE 2024; 24:238-255. [PMID: 37712883 PMCID: PMC10950347 DOI: 10.17305/bb.2023.9540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/30/2023] [Accepted: 09/14/2023] [Indexed: 09/16/2023]
Abstract
The range of clinical manifestations associated with the infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encompasses a broad spectrum, ranging from flu-like symptoms to the occurrence of multiple organ failure and death. The severity of the coronavirus disease 2019 (COVID-19) is categorized based on clinical presentation and is divided into three distinct levels of severity identified as non-severe, severe, and critical. Although individuals of all age groups are susceptible to SARS-CoV-2 infection, middle-aged and older adults are more frequently impacted, with the latter being more likely to develop severe illness. Various laboratory characteristics observed in hospitalized COVID-19 patients have been correlated with adverse outcomes. These include elevated levels of D-dimer, liver enzymes, lactate dehydrogenase, C-reactive protein, ferritin, prothrombin time, and troponin, as well as decreased lymphocyte and platelets counts. This review investigated the relationship between baseline clinical characteristics, initial laboratory parameters upon hospital admission, and the severity of illness and mortality rates among COVID-19 patients. Although the COVID-19 pandemic has concluded, understanding the laboratory predictors of virus severity and mortality remains crucial, and examining these predictors can have long-term effects. Such insights can help healthcare systems manage resources more effectively and deliver timely and appropriate care by identifying and targeting high-risk individuals. This knowledge can also help us better prepare for future pandemics. By examining these predictors, we can take steps to protect public health and mitigate the impact of future pandemics.
Collapse
Affiliation(s)
- Ahmad R Alsayed
- Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan
| | - Syed Imran Ahmed
- College of Health and Science, School of Pharmacy, University of Lincoln, Lincoln, United Kingdom
| | - Anas Osama AL Shweiki
- Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan
| | - Mustafa Al-Shajlawi
- Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan
| | - Nancy Hakooz
- School of Pharmacy, The University of Jordan, Amman, Jordan
| |
Collapse
|
20
|
Feng R, Fu S, Liu H, Wang Y, Liu S, Wang K, Chen B, Zhang X, Hu L, Chen Q, Cai T, Han X, Wang C. Single-Atom Site SERS Chip for Rapid, Ultrasensitive, and Reproducible Direct-Monitoring of RNA Binding. Adv Healthc Mater 2024; 13:e2301146. [PMID: 38176000 DOI: 10.1002/adhm.202301146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 12/11/2023] [Indexed: 01/06/2024]
Abstract
Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations.
Collapse
Affiliation(s)
- Ran Feng
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, 315012, China
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
| | - Shaohua Fu
- Key Laboratory of Luminescence and Optical Information, Ministry of Education, Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing, 100044, China
- Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China
| | | | - Ying Wang
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China
| | - Simiao Liu
- Thorgene Co., Ltd, Beijing, 100176, China
| | - Kaiwen Wang
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
| | - Binbin Chen
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
| | - Xiaoxian Zhang
- Key Laboratory of Luminescence and Optical Information, Ministry of Education, Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing, 100044, China
| | - Liming Hu
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
| | - Qian Chen
- Thorgene Co., Ltd, Beijing, 100176, China
| | - Ting Cai
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, 315012, China
| | - Xiaodong Han
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
| | - Cong Wang
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, 315012, China
- Beijing Key Laboratory of Microstructure and Properties of Solids, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China
- Thorgene Co., Ltd, Beijing, 100176, China
| |
Collapse
|
21
|
Vermeulen M, Mhlanga L, Sykes W, Cable R, Coleman C, Pietersen N, Swanevelder R, Glatt TN, Bingham J, van den Berg K, Grebe E, Welte A. The evolution and interpretation of seroprevalence of SARS-CoV-2 antibodies among South African blood donors from the Beta to Omicron variant-driven waves. Vox Sang 2024; 119:242-251. [PMID: 38156504 DOI: 10.1111/vox.13571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/14/2023] [Accepted: 11/17/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND AND OBJECTIVES Confirmed COVID-19 diagnoses underestimate the total number of infections. Blood donors can provide representative seroprevalence estimates, which can be leveraged into reasonable estimates of total infection counts and infection fatality rate (IFR). MATERIALS AND METHODS Blood donors who donated after each of three epidemic waves (Beta, Delta and first Omicron waves) were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche Elecsys anti-SARS-CoV-2 total immunoglobulin assay. Roche Elecsys anti-spike antibody testing was done for the post-Omicron sampling. Prevalence of antibodies was estimated by age, sex, race and province and compared to official case reporting. Province and age group-specific IFRs were estimated using external excess mortality estimates. RESULTS The nationally weighted anti-nucleocapsid seroprevalence estimates after the Beta, Delta and Omicron waves were 47% (46.2%-48.6%), 71% (68.8%-73.5%) and 87% (85.5%-88.4%), respectively. There was no variation by age and sex, but there were statistically and epidemiologically significant differences by province (except at the latest time point) and race. There was a 13-fold higher seroprevalence than confirmed case counts at the first time point. Age-dependent IFR roughly doubled for every 10 years of age increase over 6 decades from 0.014% in children to 6.793% in octogenarians. CONCLUSION Discrepancies were found between seroprevalence and confirmed case counts. High seroprevalence rates found among Black African donors can be ascribed to historical inequities. Our IFR estimates were useful in refining previous large disagreements about the severity of the epidemic in South Africa. Blood donor-based serosurveys provided a valuable and efficient way to provide near real-time monitoring of the ongoing SARS-CoV-2 outbreak.
Collapse
Affiliation(s)
- Marion Vermeulen
- South African National Blood Service, Johannesburg, South Africa
- University of the Free State, Bloemfontein, South Africa
| | - Laurette Mhlanga
- DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa
- Northwestern University, Chicago, Illinois, USA
| | - Wendy Sykes
- South African National Blood Service, Johannesburg, South Africa
| | | | - Charl Coleman
- South African National Blood Service, Johannesburg, South Africa
| | | | | | - Tanya Nadia Glatt
- South African National Blood Service, Johannesburg, South Africa
- University of Johannesburg, Johannesburg, South Africa
| | - Jeremy Bingham
- DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa
| | - Karin van den Berg
- South African National Blood Service, Johannesburg, South Africa
- University of the Free State, Bloemfontein, South Africa
- University of Cape Town, Rondebosch, South Africa
| | - Eduard Grebe
- DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa
- Vitalant Research Institute, San Francisco, California, USA
- University of California San Francisco, San Francisco, California, USA
| | - Alex Welte
- DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa
| |
Collapse
|
22
|
Petros BA, Milliren CE, Sabeti PC, Ozonoff A. Increased pediatric RSV case counts following the emergence of SARS-CoV-2 are attributable to increased testing. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.02.06.24302387. [PMID: 38405774 PMCID: PMC10888990 DOI: 10.1101/2024.02.06.24302387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
Background The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge. Methods We conducted a multicenter, retrospective analysis of 342,530 RSV encounters and 980,546 RSV diagnostic tests occurring at 32 United States pediatric hospitals between 2013 and 2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and testing volume, and to quantify changes in the proportions of patients admitted from the emergency department (ED), admitted to the intensive care unit (ICU), and receiving mechanical ventilation. We quantified the fraction of the observed shifts in case counts and in the age of diagnosed patients attributable to changes in RSV testing practices. Finally, we analyzed 524,404 influenza virus encounters and 1,768,526 influenza diagnostic tests to address the specificity of the findings to RSV. Findings RSV patient volume increased 2.4-fold (95% CI: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase, and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Over two-thirds of the apparent shifts in patient volume and in patient age were attributable to increased testing, which was concentrated among older pediatric patients. The proportions of patients with RSV requiring hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. These declines were not observed for patients with influenza virus. Interpretation A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. We identify expected consequences of increased testing, including the diagnosis of less severe cases and a shift in the patient age distribution. These findings warrant a critical assessment of the immunity debt hypothesis, while highlighting the importance of considering the testing denominator when surveillance strategies are dynamic. Funding National Institutes of Health & Howard Hughes Medical Institute.
Collapse
Affiliation(s)
- Brittany A. Petros
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Harvard-MIT Health Sciences & Technology, Cambridge, MA, USA
- Harvard/MIT MD-PhD Program, Boston, MA, USA
- Department of Systems Biology, Harvard Medical School, Boston, MA, USA
| | - Carly E. Milliren
- Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA, USA
| | - Pardis C. Sabeti
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA
- Department of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Howard Hughes Medical Institute, Chevy Chase, MD, USA
| | - Al Ozonoff
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Precision Vaccines Program, Boston Children’s Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
23
|
Han S, An HJ, Kwak T, Kim M, Kim D, Lee LP, Choi I. Plasmonic Optical Wells-Based Enhanced Rate PCR. NANO LETTERS 2024; 24:1738-1745. [PMID: 38286020 DOI: 10.1021/acs.nanolett.3c04615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2024]
Abstract
Rapid, sensitive, inexpensive point-of-care molecular diagnostics are crucial for the efficient control of spreading viral diseases and biosecurity of global health. However, the gold standard, polymerase chain reaction (PCR) is time-consuming and expensive and needs specialized testing laboratories. Here, we report a low-cost yet fast, selective, and sensitive Plasmonic Optical Wells-Based Enhanced Rate PCR: POWER-PCR. We optimized the efficient optofluidic design of 3D plasmonic optical wells via the computational simulation of light-to-heat conversion and thermophoretic convection in a self-created plasmonic cavity. The POWER-PCR chamber with a self-passivation layer can concentrate incident light to accumulate molecules, generate rapid heat transfer and thermophoretic flow, and minimize the quenching effect on the naked Au surface. Notably, we achieved swift photothermal cycling of nucleic acid amplification in POWER-PCR on-a-chip in 4 min 24 s. The POWER-PCR will provide an excellent solution for affordable and sensitive molecular diagnostics for precision medicine and preventive global healthcare.
Collapse
Affiliation(s)
- Seungyeon Han
- Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea
| | - Hyun Ji An
- Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea
- Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
| | - Taejin Kwak
- Department of Mechanical Engineering, Sogang University, Seoul, 04107, Republic of Korea
| | - Miseol Kim
- Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea
| | - Dongchoul Kim
- Department of Mechanical Engineering, Sogang University, Seoul, 04107, Republic of Korea
| | - Luke P Lee
- Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
- Department of Bioengineering, University of California, Berkeley, California 94720, United States
- Department of Electrical Engineering and Computer Science, University of California, Berkeley, California 94720, United States
- Institute of Quantum Biophysics, Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea
- Department of Chemistry & Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Inhee Choi
- Department of Life Science, University of Seoul, Seoul, 02504, Republic of Korea
- Department of Applied Chemistry, University of Seoul, Seoul, 02504, Republic of Korea
| |
Collapse
|
24
|
Bravo-González S, González-González E, Perales-Salinas V, Rodríguez-Sánchez IP, Ortiz-Castillo JE, Vargas-Martínez A, Perez-Gonzalez VH, Luna-Aguirre CM, Trujillo-de Santiago G, Alvarez MM. Self-Diagnosis of SARS-CoV-2 from Saliva Samples at Home: Isothermal Amplification Enabled by Do-It-Yourself Portable Incubators and Laminated Poly-ethyl Sulfonate Membranes. Diagnostics (Basel) 2024; 14:221. [PMID: 38275468 PMCID: PMC10814948 DOI: 10.3390/diagnostics14020221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/04/2023] [Accepted: 12/07/2023] [Indexed: 01/27/2024] Open
Abstract
COVID-19 made explicit the need for rethinking the way in which we conduct testing for epidemic emergencies. During the COVID-19 pandemic, the dependence on centralized lab facilities and resource-intensive methodologies (e.g., RT-qPCR methods) greatly limited the deployment of widespread testing efforts in many developed and underdeveloped countries. Here, we illustrate the development of a simple and portable diagnostic kit that enables self-diagnosis of COVID-19 at home from saliva samples. We describe the development of a do-it-yourself (DIY) incubator for Eppendorf tubes that can be used to conduct SARS-CoV-2 detection with competitive sensitivity and selectivity from saliva at home. In a proof-of-concept experiment, we assembled Eppendorf-tube incubators at our home shop, prepared a single-tube mix of reagents and LAMP primers in our lab, and deployed these COVID-19 detection kits using urban delivery systems (i.e., Rappifavor or Uber) to more than 15 different locations in Monterrey, México. This straightforward strategy enabled rapid and cost-effective at-home molecular diagnostics of SARS-CoV-2 from real saliva samples with a high sensitivity (100%) and high selectivity (87%).
Collapse
Affiliation(s)
- Sergio Bravo-González
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Bioingeniería, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico
| | - Everardo González-González
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Bioingeniería, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico
| | - Valeria Perales-Salinas
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Bioingeniería, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico
| | - Iram Pablo Rodríguez-Sánchez
- Laboratorio de Fisiología Molecular y Estructural, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66455, NL, Mexico;
- Alfa Medical Center, Guadalupe 67100, NL, Mexico
| | - Jose E. Ortiz-Castillo
- Departamento de Ingeniería Mecátrónica y Eléctrica, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (J.E.O.-C.); (A.V.-M.); (V.H.P.-G.)
| | - Adriana Vargas-Martínez
- Departamento de Ingeniería Mecátrónica y Eléctrica, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (J.E.O.-C.); (A.V.-M.); (V.H.P.-G.)
| | - Victor H. Perez-Gonzalez
- Departamento de Ingeniería Mecátrónica y Eléctrica, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (J.E.O.-C.); (A.V.-M.); (V.H.P.-G.)
| | - Claudia Maribel Luna-Aguirre
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Bioingeniería, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico
| | - Grissel Trujillo-de Santiago
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Ingeniería Mecátrónica y Eléctrica, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (J.E.O.-C.); (A.V.-M.); (V.H.P.-G.)
| | - Mario Moisés Alvarez
- Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (S.B.-G.); (E.G.-G.); (V.P.-S.); (C.M.L.-A.)
- Departamento de Ingeniería Mecátrónica y Eléctrica, Tecnologico de Monterrey, Monterrey 64849, NL, Mexico; (J.E.O.-C.); (A.V.-M.); (V.H.P.-G.)
| |
Collapse
|
25
|
Leli C, Ferrara L, Bottino P, Bara C, Megna I, Penpa S, Felici E, Maconi A, Rocchetti A. Application of a SARS-CoV-2 Antigen Rapid Immunoassay Based on Active Microfluidic Technology in a Setting of Children and Young Adults. Viruses 2023; 16:41. [PMID: 38257741 PMCID: PMC10818591 DOI: 10.3390/v16010041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/21/2023] [Accepted: 12/25/2023] [Indexed: 01/24/2024] Open
Abstract
To carry out effective and quick identification of SARS-CoV-2 from nasopharyngeal swabs and contain outbreaks, reliable and rapid tools are needed. Herein, we compared a rapid antigen test based on active microfluidic technology to an RT-qPCR assay in pediatric and young adult patients admitted to the Pediatric Emergency Unit of a Children's Hospital. Nasopharyngeal swabs collected from patients with suspected COVID-19 disease and from those without COVID-19 related symptoms, but requiring hospitalization, were performed with both antigen test and RT-qPCR assays. We included 375 patients with a median age of 5 years in the study, with an estimated overall prevalence of 7.2%. Overall, we observed a specificity of 97.4% (95% CI: 94.9-98.7) and a sensitivity of 66.6% (95% CI: 46.0-82.7) with a positive likelihood ratio (LR+) of 25.8 (95% CI: 12.8-51.8). In the subgroup of symptomatic patients, the specificity and the sensitivity were 95.2% (95% CI: 89.4-98.0) and 80.0% (95% CI: 44.2-96.5) respectively; LR+ was 16.6 (95% CI: 7.19-38.6). In the asymptomatic subset, the performance showed a specificity of 98.7% (95% CI: 95.8-99.7), a sensitivity of 58.8% (95% CI: 33.5-80.6), and an LR+ of 43.7 (95% CI: 13.3-144.0). Compared to RT-qPCR, the new microfluidic-based antigen test showed higher specificity (>95%) in the pediatric population, thus representing a suitable point-of-care testing (POCT) in a clinical setting with low prevalence of COVID-19.
Collapse
Affiliation(s)
- Christian Leli
- Microbiology and Virology Laboratory, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (C.L.); (L.F.); (C.B.); (A.R.)
| | - Lidia Ferrara
- Microbiology and Virology Laboratory, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (C.L.); (L.F.); (C.B.); (A.R.)
| | - Paolo Bottino
- Microbiology and Virology Laboratory, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (C.L.); (L.F.); (C.B.); (A.R.)
| | - Cristina Bara
- Microbiology and Virology Laboratory, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (C.L.); (L.F.); (C.B.); (A.R.)
| | - Iacopo Megna
- Research and Innovation Department (DAIRI), A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (I.M.); (S.P.); (A.M.)
| | - Serena Penpa
- Research and Innovation Department (DAIRI), A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (I.M.); (S.P.); (A.M.)
| | - Enrico Felici
- Pediatric and Pediatric Emergency Unit, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy;
| | - Antonio Maconi
- Research and Innovation Department (DAIRI), A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (I.M.); (S.P.); (A.M.)
| | - Andrea Rocchetti
- Microbiology and Virology Laboratory, A.O. “SS. Antonio e Biagio e C. Arrigo”, Via Venezia 16, 15121 Alessandria, Italy; (C.L.); (L.F.); (C.B.); (A.R.)
| |
Collapse
|
26
|
Ledda C, Motta G, Rapisarda V, Maltezou HC. Influenza immunization of healthcare personnel in the post-COVID-19 pandemic era: Still a lot to do! Vaccine X 2023; 15:100402. [PMID: 38058792 PMCID: PMC10696103 DOI: 10.1016/j.jvacx.2023.100402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 09/28/2023] [Accepted: 10/31/2023] [Indexed: 12/08/2023] Open
Abstract
Healthcare-associated influenza is frequently encountered in healthcare settings with significant morbidity and mortality among vulnerable patients, absenteeism among healthcare personnel (HCP), and interruption of healthcare services. Numerous investigations indicate that nosocomial outbreaks are often traced to HCP. Despite the international and national endorsements, seasonal influenza vaccine acceptance among HCP continues suboptimal worldwide. Infection control is the major objective for healthcare risk management in order to guarantee patient safety, limit the cost of hospitalization and assurance health management in controlling influenza seasons. Vigilance and anticipation are required as globally we are moving from a reactive COVID-19 pandemic response phase to one of planning for the co-circulation of viral respiratory infections. Declining to understand HCP perception of influenza risk and acceptance of vaccination might have impact patient safety as well as healthcare services.
Collapse
Affiliation(s)
- Caterina Ledda
- Occupational Medicine Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Giuseppe Motta
- Occupational Medicine Unit, “Garibaldi” Hospital of Catania, Catania, Italy
| | - Venerando Rapisarda
- Occupational Medicine Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
- Occupational Medicine Unit, “G. Rodolico – San Marco” University Hospital, Catania, Italy
| | - Helena C. Maltezou
- Directorate for Research, Studies and Documentation, National Public Health Organization, Athens, Greece
| |
Collapse
|
27
|
Vaughan A, Duffell E, Freidl GS, Lemos DS, Nardone A, Valenciano M, Subissi L, Bergeri I, K Broberg E, Penttinen P, Pebody R, Keramarou M. Systematic review of seroprevalence of SARS-CoV-2 antibodies and appraisal of evidence, prior to the widespread introduction of vaccine programmes in the WHO European Region, January-December 2020. BMJ Open 2023; 13:e064240. [PMID: 37931969 PMCID: PMC10632881 DOI: 10.1136/bmjopen-2022-064240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 09/04/2023] [Indexed: 11/08/2023] Open
Abstract
OBJECTIVES Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes. DESIGN A systematic review of the literature. DATA SOURCES We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO 'COVID-19 Global literature on coronavirus disease' database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control. ELIGIBILITY CRITERIA Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. DATA EXTRACTION AND SYNTHESIS At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. RESULTS In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%-12%); n=101), with the highest estimates in areas following widespread local transmission. CONCLUSIONS The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.
Collapse
Affiliation(s)
- Aisling Vaughan
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Erika Duffell
- European Centre for Disease Prevention and Control, Solna, Sweden
| | - Gudrun S Freidl
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Diogo Simão Lemos
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | | | | | | | | | - Eeva K Broberg
- European Centre for Disease Prevention and Control, Solna, Sweden
| | - Pasi Penttinen
- European Centre for Disease Prevention and Control, Solna, Sweden
| | - Richard Pebody
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Maria Keramarou
- European Centre for Disease Prevention and Control, Solna, Sweden
| |
Collapse
|
28
|
Misra P, Garg PK, Awasthi A, Kant S, Rai SK, Ahmad M, Guleria R, Deori TJ, Mandal S, Jaiswal A, Gongal G, Vishwakarma S, Bairwa M, Kumar R, Haldar P, Binayke A. Cell-Mediated Immunity (CMI) for SARS-CoV-2 Infection Among the General Population of North India: A Cross-Sectional Analysis From a Sub-sample of a Large Sero-Epidemiological Study. Cureus 2023; 15:e48824. [PMID: 38106811 PMCID: PMC10722242 DOI: 10.7759/cureus.48824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2023] [Indexed: 12/19/2023] Open
Abstract
Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination. Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-γ) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-γ ELISpot) assay was carried out to determine the levels of virus-specific IFN-γ producing cells in individual samples. Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-γ response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-γ producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status. Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated.
Collapse
Affiliation(s)
- Puneet Misra
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Pramod K Garg
- Gastroenterology, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Amit Awasthi
- Allergy and Immunology, Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, Faridabad, IND
| | - Shashi Kant
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Sanjay K Rai
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Mohammad Ahmad
- Epidemiology and Public Health, World Health Organization, New Delhi, IND
| | - Randeep Guleria
- Pulmonary, Critical Care, and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Trideep J Deori
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Suprakash Mandal
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Abhishek Jaiswal
- Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Gaurav Gongal
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Siddhesh Vishwakarma
- Allergy and Immunology, Immunology Core Laboratory, Translational Health Science and Technology Institute, Faridabad, IND
| | - Mohan Bairwa
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Rakesh Kumar
- Epidemiology and Public Health, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Partha Haldar
- Preventive Medicine, Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Akshay Binayke
- Allergy and Immunology, Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, Faridabad, IND
| |
Collapse
|
29
|
Shukla E, Choudhury L, Rastogi S, Chawla A, Bhattacharya S, Kaushik U, Mittal M, Rathore AS, Pandey G. Improved Stability and Manufacturability of Nucleocapsid Antigens for SARS-CoV2 Diagnostics through Protein Engineering. Biomolecules 2023; 13:1524. [PMID: 37892206 PMCID: PMC10604654 DOI: 10.3390/biom13101524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
The COVID-19 pandemic has had a significant impact on human health management. A rapid diagnosis of SARS-CoV2 at the point-of-care (POC) is critical to prevent disease spread. As a POC device for remote settings, a LFIA should not require cold-chain maintenance and should be kept at normal temperatures. Antigen stability can be enhanced by addressing instability issues when dealing with fragile components, such as proteinaceous capture antigens. This study used immunologically guided protein engineering to enhance the capture nucleocapsid (NP) antigen stability of SARS-CoV2. A search of the IEDB database revealed that antibodies detecting epitopes are almost uniformly distributed over NP1-419. In contrast, N-terminal stretches of NP1-419 are theoretically more unstable than C-terminal stretches. We identified NP250-365 as a NP stretch with a low instability index and B-cell epitopes. Apart from NP1-419, two other variants (NP121-419 and NP250-365) were cloned, expressed, and purified. The degradation pattern of the proteins was observed on SDS-PAGE after three days of stability studies at -20 °C, 4 °C, and 37 °C. NP1-419 was the most degraded while NP250-365 exhibited the least degradation. Also, NP1-419, NP250-365, and NP121-419 reacted with purified antibodies from COVID-19 patient serum. Our results suggest that NP250-365 may be used as a stable capture antigen in LFIA devices to detect COVID-19.
Collapse
Affiliation(s)
- Esha Shukla
- Bioprocess and Bioproduct Development Laboratory, University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi 110078, India
| | - Lipsa Choudhury
- Bioprocess and Bioproduct Development Laboratory, University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi 110078, India
| | - Saurabh Rastogi
- Bioprocess and Bioproduct Development Laboratory, University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi 110078, India
| | - Arshmeet Chawla
- Bioprocess and Bioproduct Development Laboratory, University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi 110078, India
| | - Sanghati Bhattacharya
- Department of Chemical Engineering, Indian Institute of Technology New Delhi, Hauz Khas, New Delhi 110016, India
| | - Umesh Kaushik
- Medsource Ozone Biomedicals Pvt. Ltd., Parmeshwari Colony, Faridabad 121003, India
| | - Manan Mittal
- Medsource Ozone Biomedicals Pvt. Ltd., Parmeshwari Colony, Faridabad 121003, India
| | - Anurag Singh Rathore
- Department of Chemical Engineering, Indian Institute of Technology New Delhi, Hauz Khas, New Delhi 110016, India
| | - Gaurav Pandey
- Bioprocess and Bioproduct Development Laboratory, University School of Biotechnology, Guru Gobind Singh Indraprastha University, Dwarka, New Delhi 110078, India
| |
Collapse
|
30
|
Cedro VQM, de Lima Gomes S, Simões ACCD, Sverzut TDVL, Bertti KCX, Tristão MT, Cavalcanti YW, Câmara JVF, Pereira AC. Cost-effectiveness analysis of COVID-19 tests in the unified health system. COST EFFECTIVENESS AND RESOURCE ALLOCATION 2023; 21:64. [PMID: 37705076 PMCID: PMC10498608 DOI: 10.1186/s12962-023-00469-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 08/17/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND To evaluate the cost-effectiveness ratio and economic impact of the Rapid Antigen Test (TR-Ag) to replace RT-PCR for the detection of the new Coronavirus in the Unified Health System (SUS). METHODS This is a cost-effectiveness analysis. Clinical protocols were used for the diagnosis of COVID-19 at the São José Municipal Hospital, located in the city of Itaberá-SP. The Incremental Cost-Effectiveness Ratio (ICER) was divided into two scenarios. In the first, the accuracy reported by the test manufacturers was included, and in the second, the cost resulting from a systematic review. Both were compared with the performance of the RT-PCR test. The increase in diagnoses was chosen as a health outcome and absenteeism was used as a criterion for assessing the economic impact. RESULTS The analysis resulted in incremental cost-effectiveness ratios of R$ 42,136.67 and R$ 68,329.73 for every thousand tests, according to the accuracy of the manufacturers' TR-Ag tests and what is reported in the literature in relation to RT-PCR, respectively. The average value found for the RT-PCR test (R$ 202.87) represents an increase of 165.32% in cost in relation to the value found for the TR-Ag. 4,305 tests were performed between April 2020 and December 2021 at the referral hospital. Also, maintaining the use of RT-PCR as the first choice for diagnosing COVID-19 and regulating absenteeism in the economically active population could have an impact of up to R$ 1,022,779.68 on municipal management. CONCLUSION It is concluded that the TR-Ag are configured as a cost-effective alternative for the SUS in the detection of the new Coronavirus. The strategy becomes economically favorable for the expansion of testing, combating the COVID-19 pandemic and reducing the impact on the local economy. However, studies are needed to validate the accuracy of the tests so that economic evaluations on the subject are more assertive.
Collapse
Affiliation(s)
- Vinicius Queiroz Miranda Cedro
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil.
| | - Stéfany de Lima Gomes
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| | - Ana Clara Correa Duarte Simões
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| | - Tatiana do Valle Lovato Sverzut
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| | - Keila Cristina Xavier Bertti
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| | - Marcelo Tadeu Tristão
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| | - Yuri Wanderley Cavalcanti
- Department of Clinical and Social Dentistry, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
| | - João Victor Frazão Câmara
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University Hospital, Homburg/Saar, Germany
| | - Antonio Carlos Pereira
- Department of Community Dentistry, Piracicaba Dental School, Universidade Estadual de Campinas - UNICAMP, Piracicaba, SP, Brazil
| |
Collapse
|
31
|
Rufino J, Ramírez JM, Aguilar J, Baquero C, Champati J, Frey D, Lillo RE, Fernández-Anta A. Consistent comparison of symptom-based methods for COVID-19 infection detection. Int J Med Inform 2023; 177:105133. [PMID: 37393765 DOI: 10.1016/j.ijmedinf.2023.105133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/12/2023] [Accepted: 06/19/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND During the global pandemic crisis, various detection methods of COVID-19-positive cases based on self-reported information were introduced to provide quick diagnosis tools for effectively planning and managing healthcare resources. These methods typically identify positive cases based on a particular combination of symptoms, and they have been evaluated using different datasets. PURPOSE This paper presents a comprehensive comparison of various COVID-19 detection methods based on self-reported information using the University of Maryland Global COVID-19 Trends and Impact Survey (UMD-CTIS), a large health surveillance platform, which was launched in partnership with Facebook. METHODS Detection methods were implemented to identify COVID-19-positive cases among UMD-CTIS participants reporting at least one symptom and a recent antigen test result (positive or negative) for six countries and two periods. Multiple detection methods were implemented for three different categories: rule-based approaches, logistic regression techniques, and tree-based machine-learning models. These methods were evaluated using different metrics including F1-score, sensitivity, specificity, and precision. An explainability analysis has also been conducted to compare methods. RESULTS Fifteen methods were evaluated for six countries and two periods. We identify the best method for each category: rule-based methods (F1-score: 51.48% - 71.11%), logistic regression techniques (F1-score: 39.91% - 71.13%), and tree-based machine learning models (F1-score: 45.07% - 73.72%). According to the explainability analysis, the relevance of the reported symptoms in COVID-19 detection varies between countries and years. However, there are two variables consistently relevant across approaches: stuffy or runny nose, and aches or muscle pain. CONCLUSIONS Regarding the categories of detection methods, evaluating detection methods using homogeneous data across countries and years provides a solid and consistent comparison. An explainability analysis of a tree-based machine-learning model can assist in identifying infected individuals specifically based on their relevant symptoms. This study is limited by the self-report nature of data, which cannot replace clinical diagnosis.
Collapse
Affiliation(s)
| | | | - Jose Aguilar
- IMDEA Networks Institute, 28918, Madrid, Spain; CEMISID, Universidad de Los Andes, Mérida, 5101, Venezuela; CIDITIC, Universidad EAFIT, Medellín, Colombia
| | | | | | | | | | | |
Collapse
|
32
|
Gram MA, Steenhard N, Cohen AS, Vangsted AM, Mølbak K, Jensen TG, Hansen CH, Ethelberg S. Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up. PLoS One 2023; 18:e0281972. [PMID: 37490451 PMCID: PMC10368237 DOI: 10.1371/journal.pone.0281972] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 07/12/2023] [Indexed: 07/27/2023] Open
Abstract
BACKGROUND The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark. METHODS We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design. RESULTS A total of 63.7 million PCR-tests and 60.0 million rapid antigen-tests were performed in the study period, testing 90.9% and 78.8% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time. CONCLUSION We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
Collapse
Affiliation(s)
- Mie Agermose Gram
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen S, Denmark
| | - Nina Steenhard
- TestCentre Denmark, Statens Serum Institut, Copenhagen S, Denmark
| | | | | | - Kåre Mølbak
- Division of Infectious Disease Preparedness, Statens Serum Institut, Copenhagen S, Denmark
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Thøger Gorm Jensen
- Department of Clinical Microbiology, Odense University Hospital Odense C, Odense, Denmark
- Research Unit of Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Christian Holm Hansen
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen S, Denmark
| | - Steen Ethelberg
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen S, Denmark
- Department of Public Health, Global Health Section, University of Copenhagen, Copenhagen K, Denmark
| |
Collapse
|
33
|
Kuznetsova NA, Ogarkova DA, Gushchin VA, Antipyat NА, Bacalin VV, Burgasova OA, Vasilchenko LA, Samkov AA, Simakova YV, Divisenko EV, Siniavin AE, Tkachuk AP, Kolobukhina LV, Shidlovskaya EV, Tyurin IN, Kruzhkova IS, Zlobin VI, Nikiforova MA, Odnoralov MA, Gintsburg AL. [Evaluation of the dynamics of detection of viable SARS-CoV-2 (Coronaviridae: Betacoronavirus: Sarbecovirus) in biological samples obtained from patients with COVID-19 in a health care setting, as one of the indicators of the infectivity of the virus]. Vopr Virusol 2023; 68:105-116. [PMID: 37264845 DOI: 10.36233/0507-4088-160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Indexed: 06/03/2023]
Abstract
INTRODUCTION The study of the mechanisms of transmission of the SARS-CoV-2 virus is the basis for building a strategy for anti-epidemic measures in the context of the COVID-19 pandemic. Understanding in what time frame a patient can spread SARS-CoV-2 is just as important as knowing the transmission mechanisms themselves. This information is necessary to develop effective measures to prevent infection by breaking the chains of transmission of the virus. The aim of the work is to identify the infectious SARS-CoV-2 virus in patient samples in the course of the disease and to determine the duration of virus shedding in patients with varying severity of COVID-19. MATERIALS AND METHODS In patients included in the study, biomaterial (nasopharyngeal swabs) was subjected to analysis by quantitative RT-PCR and virological determination of infectivity of the virus. RESULTS We have determined the timeframe of maintaining the infectivity of the virus in patients hospitalized with severe and moderate COVID-19. Based on the results of the study, we made an analysis of the relationship between the amount of detected SARS-CoV-2 RNA and the infectivity of the virus in vitro in patients with COVID-19. The median time of the infectious virus shedding was 8 days. In addition, a comparative analysis of different protocols for the detection of the viral RNA in relation to the identification of the infectious virus was carried out. CONCLUSION The obtained data make it possible to assess the dynamics of SARS-CoV-2 detection and viral load in patients with COVID-19 and indicate the significance of these parameters for the subsequent spread of the virus and the organization of preventive measures.
Collapse
Affiliation(s)
- N A Kuznetsova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - D A Ogarkova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - V A Gushchin
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - N А Antipyat
- Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow
| | | | | | - L A Vasilchenko
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - A A Samkov
- Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow
| | - Y V Simakova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - E V Divisenko
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - A E Siniavin
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - A P Tkachuk
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - L V Kolobukhina
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - E V Shidlovskaya
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - I N Tyurin
- Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow
| | - I S Kruzhkova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - V I Zlobin
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - M A Nikiforova
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| | - M A Odnoralov
- Infectious Clinical Hospital No. 1 of the Department of Health of the Moscow
| | - A L Gintsburg
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation
| |
Collapse
|
34
|
Evaluation of the Diagnostic Performance of a SARS-CoV-2 and Influenza A/B Combo Rapid Antigen Test in Respiratory Samples. Diagnostics (Basel) 2023; 13:diagnostics13050972. [PMID: 36900116 PMCID: PMC10000510 DOI: 10.3390/diagnostics13050972] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
This study aimed to evaluate the performance characteristics of a rapid antigen test developed to detect SARS-CoV-2 (COVID-19), influenza A virus (IAV), and influenza B virus (IBV) (flu) compared with those of the real-time reverse transcription-polymerase chain reaction (rRT-PCR) method. One hundred SARS-CoV-2, one hundred IAV, and twenty-four IBV patients whose diagnoses were confirmed by clinical and laboratory methods were included in the patient group. Seventy-six patients, who were negative for all respiratory tract viruses, were included as the control group. The Panbio™ COVID-19/Flu A&B Rapid Panel test kit was used in the assays. The sensitivity values of the kit were 97.5%, 97.9%, and 33.33% for SARS-CoV-2, IAV, and IBV, respectively, in samples with a viral load below 20 Ct values. The sensitivity values of the kit were 16.7%, 36.5%, and 11.11% for SARS-CoV-2, IAV, and IBV, respectively, in samples with a viral load above 20 Ct. The kit's specificity was 100%. In conclusion, this kit demonstrated high sensitivity to SARS-CoV-2 and IAV for viral loads below 20 Ct values, but the sensitivity values were not compatible with PCR positivity for lower viral loads over 20 Ct values. Rapid antigen tests may be preferred as a routine screening tool in communal environments, especially in symptomatic individuals, when diagnosing SARS-CoV-2, IAV, and IBV with high caution.
Collapse
|
35
|
Polyakov NJ, Som A, Mercaldo ND, Di Capua J, Little BP, Flores EJ. Rate of True-Positive Findings of COVID-19 Typical Appearance at Chest CT per RSNA Consensus Guidelines in an Increasingly Vaccinated Population. Radiology 2023; 306:e220680. [PMID: 36066367 PMCID: PMC9462593 DOI: 10.1148/radiol.220680] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background RSNA consensus guidelines for COVID-19-related chest CT are widely used but, to the knowledge of the authors, their rate of true-positive findings for COVID-19 pneumonia in vaccinated patients has not been assessed. Purpose To assess the rate of true-positive findings of typical appearance for COVID-19 at chest CT by using RSNA guidelines in fully vaccinated patients with polymerase chain reaction (PCR)-confirmed COVID-19 infection compared with unvaccinated patients. Materials and Methods Included were patients with COVID-19 who had typical appearance on chest CT images and one PCR test for COVID-19 with a positive result or two tests with negative results within 7 days of undergoing chest CT between January 2021 and January 2022 at a quaternary academic medical center. True-positive findings were defined as chest CT images interpreted as COVID-19 typical appearance and PCR-confirmed COVID-19 infection within 7 days. Logistic regression models were constructed to quantify the association between PCR results and vaccination status, vaccination status and COVID-19 variants, and vaccination status and number of months. Results Included were 652 patients (median age, 59 years; IQR, 48-72 years; 371 men [57%]) with CT scans classified as typical appearance. Of those patients, 483 (74%) were unvaccinated and 169 (26%) were fully vaccinated. The overall rate of true-positive findings on CT images rated as typical appearance was lower in vaccinated versus unvaccinated patients (70 of 169 [41%; 95% CI: 34, 49] vs 352 of 483 [73%; 95% CI: 69, 77]; odds ratio [OR], 3.8 [95% CI: 2.6, 5.5]; P < .001). Unvaccinated patients were more likely to have true-positive findings on CT images compared with fully vaccinated patients during the peaks of COVID-19 variants Alpha (OR, 16; 95% CI: 6, 42; P < .001) and Delta (OR, 8; 95% CI: 4, 16; P < .001), but no statistical differences were found during the peak of the Omicron variant (OR, 1.7; 95% CI: 0.3, 11; P = .56). Conclusion Fully vaccinated patients with confirmed COVID-19 breakthrough infections had lower rates of true-positive findings of COVID-19 typical appearance at chest CT. © RSNA, 2022 Supplemental material is available for this article.
Collapse
Affiliation(s)
- Nicole J Polyakov
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| | - Avik Som
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| | - Nathaniel D Mercaldo
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| | - John Di Capua
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| | - Brent P Little
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| | - Efrén J Flores
- From the Department of Scholarly Engagement, Harvard Medical School, 25 Shattuck St, Boston, MA 02115 (N.J.P., E.J.F.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (A.S., N.D.M., J.D.C., E.J.F.); and Department of Radiology, Mayo Clinic Florida, Jacksonville, Fla (B.P.L.)
| |
Collapse
|
36
|
Ceccon DM, Amaral PHR, Andrade LM, da Silva MIN, Andrade LAF, Moraes TFS, Bagno FF, Rocha RP, de Almeida Marques DP, Ferreira GM, Lourenço AA, Ribeiro ÁL, Coelho-dos-Reis JGA, da Fonseca FG, Gonzalez JC. New, fast, and precise method of COVID-19 detection in nasopharyngeal and tracheal aspirate samples combining optical spectroscopy and machine learning. Braz J Microbiol 2023:10.1007/s42770-023-00923-5. [PMID: 36854899 PMCID: PMC9974055 DOI: 10.1007/s42770-023-00923-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 02/07/2023] [Indexed: 03/02/2023] Open
Abstract
Fast, precise, and low-cost diagnostic testing to identify persons infected with SARS-CoV-2 virus is pivotal to control the global pandemic of COVID-19 that began in late 2019. The gold standard method of diagnostic recommended is the RT-qPCR test. However, this method is not universally available, and is time-consuming and requires specialized personnel, as well as sophisticated laboratories. Currently, machine learning is a useful predictive tool for biomedical applications, being able to classify data from diverse nature. Relying on the artificial intelligence learning process, spectroscopic data from nasopharyngeal swab and tracheal aspirate samples can be used to leverage characteristic patterns and nuances in healthy and infected body fluids, which allows to identify infection regardless of symptoms or any other clinical or laboratorial tests. Hence, when new measurements are performed on samples of unknown status and the corresponding data is submitted to such an algorithm, it will be possible to predict whether the source individual is infected or not. This work presents a new methodology for rapid and precise label-free diagnosing of SARS-CoV-2 infection in clinical samples, which combines spectroscopic data acquisition and analysis via artificial intelligence algorithms. Our results show an accuracy of 85% for detection of SARS-CoV-2 in nasopharyngeal swab samples collected from asymptomatic patients or with mild symptoms, as well as an accuracy of 97% in tracheal aspirate samples collected from critically ill COVID-19 patients under mechanical ventilation. Moreover, the acquisition and processing of the information is fast, simple, and cheaper than traditional approaches, suggesting this methodology as a promising tool for biomedical diagnosis vis-à-vis the emerging and re-emerging viral SARS-CoV-2 variant threats in the future.
Collapse
Affiliation(s)
- Denny M. Ceccon
- Departamento de Física, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Campus Pampulha 31270-901, Belo Horizonte, Minas Gerais 6627 Brazil
| | - Paulo Henrique R. Amaral
- Departamento de Física, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Campus Pampulha 31270-901, Belo Horizonte, Minas Gerais 6627 Brazil
| | - Lídia M. Andrade
- Departamento de Física, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Campus Pampulha 31270-901, Belo Horizonte, Minas Gerais 6627 Brazil
| | - Maria I. N. da Silva
- Departamento de Física, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Campus Pampulha 31270-901, Belo Horizonte, Minas Gerais 6627 Brazil
| | - Luis A. F. Andrade
- Centro de Tecnologia Em Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Thais F. S. Moraes
- Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Flavia F. Bagno
- Centro de Tecnologia Em Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Raissa P. Rocha
- Centro de Tecnologia Em Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Geovane Marques Ferreira
- Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Alice Aparecida Lourenço
- Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ágata Lopes Ribeiro
- Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Jordana G. A. Coelho-dos-Reis
- Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Flavio G. da Fonseca
- Centro de Tecnologia Em Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil ,Laboratório de Virologia Básica E Aplicada, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - J. C. Gonzalez
- Departamento de Física, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, Campus Pampulha 31270-901, Belo Horizonte, Minas Gerais 6627 Brazil
| |
Collapse
|
37
|
Clinical Evaluation of an Antigen Home Test Using Surface-Enhanced Raman Spectroscopy and Stacking Pad for SARS-CoV-2 Screening with Nasal and Salivary Swab Samples. Diagnostics (Basel) 2023; 13:diagnostics13050880. [PMID: 36900022 PMCID: PMC10000415 DOI: 10.3390/diagnostics13050880] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 03/03/2023] Open
Abstract
This prospective study aimed to evaluate the performance of the InstaView COVID-19 (coronavirus diseases 2019) Antigen Home Test (InstaView AHT) which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. In this test kit, surface-enhanced Raman spectroscopy was used, a stacking pad was inserted, and nasal swab and salivary swab samples were used simultaneously to improve performance. The clinical performance of the InstaView AHT was compared to that of RT-PCR using nasopharyngeal samples. The participants without any prior training were recruited and performed the sample collection, testing, and interpretation of the results by themselves. Of the 91 PCR-positive patients, 85 had positive InstaView AHT results. The sensitivity and specificity of the InstaView AHT were 93.4% (95% confidence interval [CI]: 86.2-97.5) and 99.4% (95% CI: 98.2-99.9). The sensitivity of the InstaView AHT was above 90% for all samples obtained from patients with Ct ≤ 20, 20 < Ct ≤ 25, and 25 < Ct ≤ 30 (100%, 95.1%, and 92.0%, respectively). The InstaView AHT can be used as an alternative to RT-PCR testing because of its relatively high sensitivity and specificity, especially when SARS-CoV-2 prevalence is high, and the availability of RT-PCR testing is limited.
Collapse
|
38
|
Mohammad S, Wang Y, Cordero J, Watson C, Molestina R, Rashid S, Bradford R. Development and validation of a rapid and easy-to-perform point-of-care lateral flow immunoassay (LFIA) for the detection of SARS-CoV-2 spike protein. Front Immunol 2023; 14:1111644. [PMID: 36911726 PMCID: PMC9995903 DOI: 10.3389/fimmu.2023.1111644] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/31/2023] [Indexed: 02/25/2023] Open
Abstract
Development and validation of rapid and easy-to-perform diagnostics continue to be a high priority during the current COVID-19 pandemic. Although vaccines are now widely available, early detection and consistent transmission control provide ideal means to mitigate the spread of SARS-CoV-2. Nucleic acid-based real-time PCR tests are widely acknowledged as the gold standard for reliable diagnosis of COVID-19 infection. These tests are based on detecting viable or nonviable viral nucleic acids. SARS-CoV-2 spike protein is an alternative and ideal target for SARS-CoV-2 diagnosis in the early phase of infection, but point-of-care kits to detect the SARS-CoV-2 spike protein are limited. Here we describe a rapid and convenient method based on Lateral Flow Immunoassay (LFIA) to detect SARS-CoV-2 spike proteins, including SARS-CoV-2 variants (A.23.1, B.1.1.1, 1.617.2, B.1.1.7, B.1.351, P.1, N501Y, R.1, P681H, P3, UK, and South African) within 5 to 10 minutes. We generated highly specific monoclonal antibodies (mAbs) against rationally designed SARS-CoV-2 spike protein. Matched pair mAbs were selected by epitope mapping and employed as antigen capture reagents by spotting onto a nitrocellulose membrane and as detector reagents by conjugation with colloidal gold nanoparticles. We evaluated the performance of the LFIA using recombinant spike proteins of SARS-CoV-2 and several SARS-CoV-2 variants. The specificity of the LFIA was assessed using heat-inactivated SARS-CoV-2 and related human coronaviruses (HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63) and an FDA-approved respiratory pathogens (RP) panel. The assay exhibited 98% specificity and acceptable performance with respect to the minimum limit of detection (25 ng/test) in validation tests. This new LFIA provides improved performance for the early diagnosis of SARS-CoV-2, particularly for home monitoring and in situations with limited access to molecular methods.
Collapse
Affiliation(s)
- Shamim Mohammad
- American Type Culture Collection, Manassas, VA, United States
| | | | | | | | | | | | | |
Collapse
|
39
|
Chabi M, Vu B, Brosamer K, Smith M, Chavan D, Conrad JC, Willson RC, Kourentzi K. Smartphone-read phage lateral flow assay for point-of-care detection of infection. Analyst 2023; 148:839-848. [PMID: 36645184 PMCID: PMC10503656 DOI: 10.1039/d2an01499h] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
The COVID-19 pandemic has highlighted the urgent need for sensitive, affordable, and widely accessible testing at the point of care. Here we demonstrate a new, universal LFA platform technology using M13 phage conjugated with antibodies and HRP enzymes that offers high analytical sensitivity and excellent performance in a complex clinical matrix. We also report its complete integration into a sensitive chemiluminescence-based smartphone-readable lateral flow assay for the detection of SARS-CoV-2 nucleoprotein. We screened 84 anti-nucleoprotein monoclonal antibody pairs in phage LFA and identified an antibody pair that gave an LoD of 25 pg mL-1 nucleoprotein in nasal swab extract using a FluorChem gel documentation system and 100 pg mL-1 when the test was imaged and analyzed by an in-house-developed smartphone reader. The smartphone-read LFA signals for positive clinical samples tested (N = 15, with known Ct) were statistically different (p < 0.001) from signals for negative clinical samples (N = 11). The phage LFA technology combined with smartphone chemiluminescence imaging can enable the timely development of ultrasensitive, affordable point-of-care testing platforms for SARS-CoV-2 and beyond.
Collapse
Affiliation(s)
- Maede Chabi
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.
| | - Binh Vu
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
| | - Kristen Brosamer
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.
| | - Maxwell Smith
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
| | - Dimple Chavan
- Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA
| | - Jacinta C Conrad
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
| | - Richard C Willson
- Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
- Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA
- Escuela de Medicina y Ciencias de Salud, Tecnológico de Monterrey, Monterrey, Nuevo León 64710, Mexico
| | - Katerina Kourentzi
- Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
| |
Collapse
|
40
|
Azam T, Bukhari SH, Liaqat U, Miran W. Emerging Methods in Biosensing of Immunoglobin G-A Review. SENSORS (BASEL, SWITZERLAND) 2023; 23:676. [PMID: 36679468 PMCID: PMC9862834 DOI: 10.3390/s23020676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/30/2022] [Accepted: 01/01/2023] [Indexed: 06/17/2023]
Abstract
Human antibodies are produced due to the activation of immune system components upon exposure to an external agent or antigen. Human antibody G, or immunoglobin G (IgG), accounts for 75% of total serum antibody content. IgG controls several infections by eradicating disease-causing pathogens from the body through complementary interactions with toxins. Additionally, IgG is an important diagnostic tool for certain pathological conditions, such as autoimmune hepatitis, hepatitis B virus (HBV), chickenpox and MMR (measles, mumps, and rubella), and coronavirus-induced disease 19 (COVID-19). As an important biomarker, IgG has sparked interest in conducting research to produce robust, sensitive, selective, and economical biosensors for its detection. To date, researchers have used different strategies and explored various materials from macro- to nanoscale to be used in IgG biosensing. In this review, emerging biosensors for IgG detection have been reviewed along with their detection limits, especially electrochemical biosensors that, when coupled with nanomaterials, can help to achieve the characteristics of a reliable IgG biosensor. Furthermore, this review can assist scientists in developing strategies for future research not only for IgG biosensors but also for the development of other biosensing systems for diverse targets.
Collapse
Affiliation(s)
- Tehmina Azam
- School of Chemical and Materials Engineering (SCME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
| | - Syed Hassan Bukhari
- College of Computational Sciences and Natural Sciences, Minerva University, San Francisco, CA 94103, USA
| | - Usman Liaqat
- School of Chemical and Materials Engineering (SCME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
| | - Waheed Miran
- School of Chemical and Materials Engineering (SCME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
| |
Collapse
|
41
|
Quraishi E, Jibuaku C, Lisik D, Wennergren G, Lötvall J, Nyberg F, Ekerljung L, Rådinger M, Kankaanranta H, Nwaru BI. Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden. Respir Res 2023; 24:10. [PMID: 36631852 PMCID: PMC9832414 DOI: 10.1186/s12931-023-02315-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 01/04/2023] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.
Collapse
Affiliation(s)
- Eman Quraishi
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Chiamaka Jibuaku
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Daniil Lisik
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Göran Wennergren
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden ,grid.8761.80000 0000 9919 9582Department of Paediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Jan Lötvall
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Fredrik Nyberg
- grid.8761.80000 0000 9919 9582School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Linda Ekerljung
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Madeleine Rådinger
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Hannu Kankaanranta
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden ,grid.502801.e0000 0001 2314 6254Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland ,grid.415465.70000 0004 0391 502XDepartment of Respiratory Medicine, Seinäjoki Central Hospital, Tampere, Finland
| | - Bright I. Nwaru
- grid.8761.80000 0000 9919 9582Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden ,grid.8761.80000 0000 9919 9582Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
42
|
HEIDARI FATEMEH, SEYEDEBRAHIMI REIHANEH, YANG PIAO, FARSANI MOHSENESLAMI, ABABZADEH SHIMA, KALHOR NASER, MANOOCHEHRI HAMED, SHEYKHHASAN MOHSEN, AZIMZADEH MARYAM. Exosomes in viral infection: Effects for pathogenesis and treatment strategies. BIOCELL 2023; 47:2597-2608. [DOI: 10.32604/biocell.2023.043351] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
|
43
|
Fourie E, Sijm YEE, Badoux P, Mérelle ME, Haverkort ME, Euser SM, van Houten MA. High detection rate of viral pathogens in nasal discharge in children aged 0 till 5 years. J Med Virol 2023; 95:e28415. [PMID: 36541735 DOI: 10.1002/jmv.28415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/28/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
Respiratory tract infections (RTI) in children remain a cause of disease burden worldwide. Nasopharyngeal (NP) & oropharyngeal (OP) swabs are used for respiratory pathogen detection, but hold disadvantages particularly for children, highlighting the importance and preference for a child friendly detection method. We aimed to evaluate the performance and tolerability of a rhinorrhea swab (RS) in detecting viral pathogens when compared to a combined OP(/NP) or mid-turbinate (MT) nasal swab. This study was conducted between September 2021 and July 2022 in the Netherlands. Children aged 0-5 years, with an upper RTI and nasal discharge, were included and received a combined swab and a RS. Multiplex polymerase chain reaction (PCR) and severe acute respiratory syndrome coronavirus-2 PCR were used for viral pathogen detection. Tolerability was evaluated with a questionnaire and visual analog scale (VAS) scores. During 11 months 88 children were included, with a median age of 1.00 year [interquartile range 0.00-3.00]. In total 122 viral pathogens were detected in 81 children (92%). Sensitivity and specificity of the RS compared to a combined swab were respectively 97% (95% confidence interval [CI] 91%-100%) and 78% (95% CI 45%-94%). Rhinorrhea samples detected more pathogens than the (combined) nasal samples, 112 versus 108 respectively. Median VAS scores were significantly lower for the RS in both children (2 vs. 6) and their parents (0 vs. 5). A RS can therefore just as effectively/reliably detect viral pathogens as the combined swab in young children and is better tolerated by both children and their parents/caregivers.
Collapse
Affiliation(s)
- Elandri Fourie
- Spaarne Gasthuis Academy, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Yara E E Sijm
- Spaarne Gasthuis Academy, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Paul Badoux
- Regional Public Health Laboratory Kennemerland, Haarlem, The Netherlands
| | - Marieke E Mérelle
- Department of Pediatrics, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | | | - Sjoerd M Euser
- Regional Public Health Laboratory Kennemerland, Haarlem, The Netherlands
| | - Marlies A van Houten
- Spaarne Gasthuis Academy, Spaarne Gasthuis, Hoofddorp, The Netherlands.,Department of Pediatrics, Spaarne Gasthuis, Hoofddorp, The Netherlands
| |
Collapse
|
44
|
Martín-Rodríguez F, Sanz-García A, Ortega GJ, Delgado-Benito JF, García Villena E, Mazas Pérez-Oleaga C, López-Izquierdo R, Castro Villamor MA. One-on-one comparison between qCSI and NEWS scores for mortality risk assessment in patients with COVID-19. Ann Med 2022; 54:646-654. [PMID: 35193439 PMCID: PMC8881067 DOI: 10.1080/07853890.2022.2042590] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVE To compare the predictive value of the quick COVID-19 Severity Index (qCSI) and the National Early Warning Score (NEWS) for 90-day mortality amongst COVID-19 patients. METHODS Multicenter retrospective cohort study conducted in adult patients transferred by ambulance to an emergency department (ED) with suspected COVID-19 infection subsequently confirmed by a SARS-CoV-2 test (polymerase chain reaction). We collected epidemiological data, clinical covariates (respiratory rate, oxygen saturation, systolic blood pressure, heart rate, temperature, level of consciousness and use of supplemental oxygen) and hospital variables. The primary outcome was cumulative all-cause mortality during a 90-day follow-up, with mortality assessment monitoring time points at 1, 2, 7, 14, 30 and 90 days from ED attendance. Comparison of performances for 90-day mortality between both scores was carried out by univariate analysis. RESULTS From March to November 2020, we included 2,961 SARS-CoV-2 positive patients (median age 79 years, IQR 66-88), with 49.2% females. The qCSI score provided an AUC ranging from 0.769 (1-day mortality) to 0.749 (90-day mortality), whereas AUCs for NEWS ranging from 0.825 for 1-day mortality to 0.777 for 90-day mortality. At all-time points studied, differences between both scores were statistically significant (p < .001). CONCLUSION Patients with SARS-CoV-2 can rapidly develop bilateral pneumonias with multiorgan disease; in these cases, in which an evacuation by the EMS is required, reliable scores for an early identification of patients with risk of clinical deterioration are critical. The NEWS score provides not only better prognostic results than those offered by qCSI at all the analyzed time points, but it is also better suited for COVID-19 patients.KEY MESSAGESThis work aims to determine whether NEWS is the best score for mortality risk assessment in patients with COVID-19.AUCs for NEWS ranged from 0.825 for 1-day mortality to 0.777 for 90-day mortality and were significantly higher than those for qCSI in these same outcomes.NEWS provides a better prognostic capacity than the qCSI score and allows for long-term (90 days) mortality risk assessment of COVID-19 patients.
Collapse
Affiliation(s)
- Francisco Martín-Rodríguez
- Unidad Móvil de Emergencias Valladolid I, Gerencia de Emergencias Sanitarias, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain.,Centro de Simulación Clínica Avanzada, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain
| | - Ancor Sanz-García
- Data Analysis Unit, Instituto de Investigación Sanitaria del Hospital de la Princesa (IIS-IP), Madrid, Spain
| | - Guillermo J Ortega
- Data Analysis Unit, Instituto de Investigación Sanitaria del Hospital de la Princesa (IIS-IP), Madrid, Spain.,Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina
| | - Juan F Delgado-Benito
- Unidad Móvil de Emergencias de Salamanca, Gerencia de Emergencias Sanitarias, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain
| | - Eduardo García Villena
- Escuela Politécnica Superior, Universidad Europea del Atlántico, Santander, Spain.,Departamento de Medio Ambiente y Sostenibilidad, Universidad Internacional Iberoamericana, Arecibo, Puerto Rico (EE.UU)
| | | | - Raúl López-Izquierdo
- Servicio de Urgencias, Hospital Universitario Rio Hortega de Valladolid, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain
| | - Miguel A Castro Villamor
- Centro de Simulación Clínica Avanzada, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain
| |
Collapse
|
45
|
Rapid detection of φX-174 virus based on synchronous fluorescence of tryptophan. Anal Bioanal Chem 2022; 415:509-515. [PMID: 36441232 PMCID: PMC9702944 DOI: 10.1007/s00216-022-04436-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/29/2022]
Abstract
The development of rapid methods for the detection of virus particles based on their intrinsic fluorescence (the native auto-fluorescence that originates from the non-labeled analyte) is challenging. Pure viruses may be detected in filtered solutions, based on the strong fluorescence of the amino acid tryptophan (Trp) in their proteins. Nevertheless, Trp also exists in high quantities in the hosts and host cultivation media. In this work, we developed a new method for the detection of the naked φX-174 virus. We show that a separation of φX-174 from its Escherichia coli host (grown on the standard cultivation medium nutrient agar) by simple extraction and filtration is not sufficient for its detection based on the intrinsic fluorescence since ~ 70% of the Trp fluorescence is derived from impurities. We formulate a new cultivation medium with a very low Trp concentration. We apply synchronous fluorescence measurements to show that no Trp fluorescence is detected in the extract solution upon incubation of this medium substrate with ammonium acetate extraction buffer. Finally, we apply synchronous fluorescence to detect φX-174 based on the spectral fingerprint of its native Trp content. Such a method is more rapid than usual traditional separation and detection methods which can take several hours and does not require any addition of labeling agents such as fluorescent dyes or antibodies for the detection. As other virus species contain Trp as one of the amino acids presents in their proteins, this method has the potential to apply to the detection of other viral species.
Collapse
|
46
|
Valenzuela-Fernández A, Cabrera-Rodriguez R, Ciuffreda L, Perez-Yanes S, Estevez-Herrera J, González-Montelongo R, Alcoba-Florez J, Trujillo-González R, García-Martínez de Artola D, Gil-Campesino H, Díez-Gil O, Lorenzo-Salazar JM, Flores C, Garcia-Luis J. Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19. Front Bioeng Biotechnol 2022; 10:1052436. [PMID: 36507266 PMCID: PMC9732709 DOI: 10.3389/fbioe.2022.1052436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/09/2022] [Indexed: 11/26/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the associated coronavirus disease 2019 (COVID-19), which severely affect the respiratory system and several organs and tissues, and may lead to death, have shown how science can respond when challenged by a global emergency, offering as a response a myriad of rapid technological developments. Development of vaccines at lightning speed is one of them. SARS-CoV-2 outbreaks have stressed healthcare systems, questioning patients care by using standard non-adapted therapies and diagnostic tools. In this scenario, nanotechnology has offered new tools, techniques and opportunities for prevention, for rapid, accurate and sensitive diagnosis and treatment of COVID-19. In this review, we focus on the nanotechnological applications and nano-based materials (i.e., personal protective equipment) to combat SARS-CoV-2 transmission, infection, organ damage and for the development of new tools for virosurveillance, diagnose and immune protection by mRNA and other nano-based vaccines. All the nano-based developed tools have allowed a historical, unprecedented, real time epidemiological surveillance and diagnosis of SARS-CoV-2 infection, at community and international levels. The nano-based technology has help to predict and detect how this Sarbecovirus is mutating and the severity of the associated COVID-19 disease, thereby assisting the administration and public health services to make decisions and measures for preparedness against the emerging variants of SARS-CoV-2 and severe or lethal COVID-19.
Collapse
Affiliation(s)
- Agustín Valenzuela-Fernández
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | - Romina Cabrera-Rodriguez
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | - Laura Ciuffreda
- Research Unit, Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain
| | - Silvia Perez-Yanes
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | - Judith Estevez-Herrera
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | | | - Julia Alcoba-Florez
- Servicio de Microbiología, Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain
| | - Rodrigo Trujillo-González
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
- Departamento de Análisis Matemático, Facultad de Ciencias, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
| | | | - Helena Gil-Campesino
- Servicio de Microbiología, Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain
| | - Oscar Díez-Gil
- Servicio de Microbiología, Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain
| | - José M. Lorenzo-Salazar
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
| | - Carlos Flores
- Research Unit, Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
- Faculty of Health Sciences, University of Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
| | - Jonay Garcia-Luis
- Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| |
Collapse
|
47
|
SARS-CoV-2 Morphometry Analysis and Prediction of Real Virus Levels Based on Full Recurrent Neural Network Using TEM Images. Viruses 2022; 14:v14112386. [PMID: 36366485 PMCID: PMC9698148 DOI: 10.3390/v14112386] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/23/2022] [Accepted: 10/24/2022] [Indexed: 01/31/2023] Open
Abstract
The SARS-CoV-2 virus is responsible for the rapid global spread of the COVID-19 disease. As a result, it is critical to understand and collect primary data on the virus, infection epidemiology, and treatment. Despite the speed with which the virus was detected, studies of its cell biology and architecture at the ultrastructural level are still in their infancy. Therefore, we investigated and analyzed the viral morphometry of SARS-CoV-2 to extract important key points of the virus's characteristics. Then, we proposed a prediction model to identify the real virus levels based on the optimization of a full recurrent neural network (RNN) using transmission electron microscopy (TEM) images. Consequently, identification of virus levels depends on the size of the morphometry of the area (width, height, circularity, roundness, aspect ratio, and solidity). The results of our model were an error score of training network performance 3.216 × 10-11 at 639 epoch, regression of -1.6 × 10-9, momentum gain (Mu) 1 × 10-9, and gradient value of 9.6852 × 10-8, which represent a network with a high ability to predict virus levels. The fully automated system enables virologists to take a high-accuracy approach to virus diagnosis, prevention of mutations, and life cycle and improvement of diagnostic reagents and drugs, adding a point of view to the advancement of medical virology.
Collapse
|
48
|
Tokuyama-Toda R, Terada-Ito C, Muraoka M, Horiuchi T, Amemiya T, Fukuoka A, Hamada Y, Takebe Y, Ogawa T, Fujii S, Kikuta T, Sejima S, Satomura K. Improving the Detection Sensitivity of a New Rapid Diagnostic Technology for Severe Acute Respiratory Syndrome Coronavirus 2 Using a Trace Amount of Saliva. Diagnostics (Basel) 2022; 12:2568. [PMID: 36359412 PMCID: PMC9689209 DOI: 10.3390/diagnostics12112568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/11/2022] [Accepted: 10/20/2022] [Indexed: 09/23/2024] Open
Abstract
The early diagnosis and isolation of infected individuals with coronavirus disease 2019 (COVID-19) remain important. Although quantitative polymerase chain reaction (qPCR) testing is considered the most accurate test available for COVID-19 diagnosis, it has some limitations, such as the need for specialized laboratory technicians and a long turnaround time. Therefore, we have established and reported a rapid diagnostic method using a small amount of saliva as a sample using a lightweight mobile qPCR device. This study aimed to improve the existing method and increase the detection sensitivity and specificity. The detection specificity of CDC N1 and N2 was examined by improving qPCR reagents and polymerase chain reaction conditions for the previously reported method. Furthermore, the feasibility of detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA was examined using both the previous method and the improved method in patients with COVID-19. The results showed that the improved method increased the specificity and sensitivity. This improved method is useful for the rapid diagnosis of SARS-CoV-2.
Collapse
Affiliation(s)
- Reiko Tokuyama-Toda
- Department of Oral Medicine and Stomatology, School of Dental Medicine, Tsurumi University, 2-1-3, Tsurumi, Tsurumi-ku, Yokohama City 230-8501, Kanagawa, Japan
| | - Chika Terada-Ito
- Department of Oral Medicine and Stomatology, School of Dental Medicine, Tsurumi University, 2-1-3, Tsurumi, Tsurumi-ku, Yokohama City 230-8501, Kanagawa, Japan
| | - Masaaki Muraoka
- Certified Non-Profit Organization Biomedical Science Association, 2-20-8, Kamiosaki, Shinagawa-ku 141-0021, Tokyo, Japan
| | - Toshikatsu Horiuchi
- Department of Oral and Maxillofacial Surgery, Saiseikai Yokohamashi Tobu Hospital, 3-6-1, Shimosueyoshi, Tsurumi-ku, Yokohama City 230-8765, Kanagawa, Japan
| | - Tsuyoshi Amemiya
- Department of Oral and Maxillofacial Surgery, Saiseikai Yokohamashi Tobu Hospital, 3-6-1, Shimosueyoshi, Tsurumi-ku, Yokohama City 230-8765, Kanagawa, Japan
| | - Airi Fukuoka
- Department of Oral and Maxillofacial Surgery, Saiseikai Yokohamashi Tobu Hospital, 3-6-1, Shimosueyoshi, Tsurumi-ku, Yokohama City 230-8765, Kanagawa, Japan
| | - Yoshiki Hamada
- Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3, Tsu-rumi, Tsurumi-ku, Yokohama City 230-8501, Kanagawa, Japan
| | - Yusuke Takebe
- Department of Oral Medicine and Stomatology, School of Dental Medicine, Tsurumi University, 2-1-3, Tsurumi, Tsurumi-ku, Yokohama City 230-8501, Kanagawa, Japan
| | - Takashi Ogawa
- Department of Oral and Maxillofacial Surgery, Tokyo Medical University Hachioji Medical Center, 1163, Tatemachi, Hachioji City 193-0998, Tokyo, Japan
| | - Seiko Fujii
- Department of Oral and Maxillofacial Surgery, Shin-Yurigaoka General Hospital, 255, Furusawatsuko, Asao-ku, Kawasaki City 215-0026, Kanagawa, Japan
| | - Toshihiro Kikuta
- Department of Oral and Maxillofacial Surgery, Shin-Yurigaoka General Hospital, 255, Furusawatsuko, Asao-ku, Kawasaki City 215-0026, Kanagawa, Japan
| | - Shunsuke Sejima
- Certified Non-Profit Organization Biomedical Science Association, 2-20-8, Kamiosaki, Shinagawa-ku 141-0021, Tokyo, Japan
| | - Kazuhito Satomura
- Department of Oral Medicine and Stomatology, School of Dental Medicine, Tsurumi University, 2-1-3, Tsurumi, Tsurumi-ku, Yokohama City 230-8501, Kanagawa, Japan
| |
Collapse
|
49
|
Islam A, Hossen F, Rahman A, Sultana KF, Hasan MN, Haque A, Sosa-Hernández JE, Oyervides-Muñoz MA, Parra-Saldívar R, Ahmed T, Islam T, Dhama K, Sangkham S, Bahadur NM, Reza HM, Jakariya, Al Marzan A, Bhattacharya P, Sonne C, Ahmed F. An opinion on Wastewater-Based Epidemiological Monitoring (WBEM) with Clinical Diagnostic Test (CDT) for detecting high-prevalence areas of community COVID-19 Infections. CURRENT OPINION IN ENVIRONMENTAL SCIENCE & HEALTH 2022; 31:100396. [PMID: 36320818 PMCID: PMC9612100 DOI: 10.1016/j.coesh.2022.100396] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 02/17/2024]
Abstract
Wastewater-Based Epidemiological Monitoring (WBEM) is an efficient surveillance tool during the COVID-19 pandemic as it meets all requirements of a complete monitoring system including early warning, tracking the current trend, prevalence of the disease, detection of genetic diversity as well asthe up-surging SARS-CoV-2 new variants with mutations from the wastewater samples. Subsequently, Clinical Diagnostic Test is widely acknowledged as the global gold standard method for disease monitoring, despite several drawbacks such as high diagnosis cost, reporting bias, and the difficulty of tracking asymptomatic patients (silent spreaders of the COVID-19 infection who manifest nosymptoms of the disease). In this current reviewand opinion-based study, we first propose a combined approach) for detecting COVID-19 infection in communities using wastewater and clinical sample testing, which may be feasible and effective as an emerging public health tool for the long-term nationwide surveillance system. The viral concentrations in wastewater samples can be used as indicatorsto monitor ongoing SARS-CoV-2 trends, predict asymptomatic carriers, and detect COVID-19 hotspot areas, while clinical sampleshelp in detecting mostlysymptomaticindividuals for isolating positive cases in communities and validate WBEM protocol for mass vaccination including booster doses for COVID-19.
Collapse
Affiliation(s)
- Aminul Islam
- COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
- Advanced Molecular Lab, Department of Microbiology, President Abdul Hamid Medical College, Karimganj, Kishoreganj, Bangladesh
| | - Foysal Hossen
- COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Arifur Rahman
- COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Khandokar Fahmida Sultana
- COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Mohammad Nayeem Hasan
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
- Joint Rohingya Response Program, Food for the Hungry, Cox's Bazar, Bangladesh
| | - Atiqul Haque
- Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China
- Department of Microbiology, Faculty of Veterinary and Animal Science, Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh
| | | | | | | | - Tanvir Ahmed
- Department of Civil Engineering, Bangladesh University of Engineering and Technology, Dhaka-1000, Bangladesh
| | | | - Kuldeep Dhama
- Indian Veterinary Research Institute, Izzatnagar-243 122, Bareilly, Uttar Pradesh, India
| | - Sarawut Sangkham
- Department of Environmental Health, School of Public Health, University of Phayao, Muang District, 56000, Phayao, Thailand
| | - Newaz Mohammed Bahadur
- Department of Applied Chemistry and Chemical Engineering, Noakhali Science and TechnologyUniversity, Noakhali-3814, Bangladesh
| | - Hasan Mahmud Reza
- Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, Bangladesh
| | - Jakariya
- Department of Environmental Science and Management, North South University, Bashundhara, Dhaka-1229, Bangladesh
| | - Abdullah Al Marzan
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Prosun Bhattacharya
- COVID-19 Research@KTH, Department of Sustainable Development, Environmental Science and Engineering, KTH Royal Institute of Technology, Teknikringen 10B, SE 114 28 Stockholm, Sweden
| | - Christian Sonne
- Department of Bioscience, Arctic Research Centre (ARC), Faculty of Science and Technology, Aarhus University, Frederiksborgvej 399, PO Box 358, 4000 Roskilde, Denmark
| | - Firoz Ahmed
- COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| |
Collapse
|
50
|
Dos Santos PG, Vieira HCVS, Wietholter V, Gallina JP, Andrade TR, Marinowic DR, Zanirati GG, da Costa JC. When to test for COVID-19 using real-time reverse transcriptase polymerase chain reaction: a systematic review. Int J Infect Dis 2022; 123:58-69. [PMID: 35760382 PMCID: PMC9233872 DOI: 10.1016/j.ijid.2022.06.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/18/2022] [Accepted: 06/21/2022] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the time in days between symptom onset and first positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for COVID-19. METHODS This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR", and "diagnosis". RESULTS The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and six were cross-sectional studies. The overall mean time between symptom onset and positive test result was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR test results; the best performance was on days 22-24, when 98% of test results were positive. CONCLUSION These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing.
Collapse
Affiliation(s)
- Paula Gabrielli Dos Santos
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Helena Cristina Valentini Speggiorin Vieira
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Vinícius Wietholter
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - João Pedro Gallina
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Thomás Ranquetat Andrade
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Undergraduate Research Program, School of Medicine and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Daniel Rodrigo Marinowic
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Gabriele Goulart Zanirati
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil
| | - Jaderson Costa da Costa
- Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Biomedical Gerontology, Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul (PUCRS) School of Medicine, Porto Alegre, Brazil.
| |
Collapse
|