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Parlițeanu OA, Bălteanu MA, Zaharia DC, Constantinescu T, Cristea AM, Dumitrache-Rujinscki Ș, Nica AE, Voineag C, Alexe OS, Tabacu E, Croitoru A, Strâmbu I, Nemeș RM, Mahler B. The Impact of SARS-CoV-2 Infection on Glucose Homeostasis in Hospitalized Patients with Pulmonary Impairment. Diagnostics (Basel) 2025; 15:554. [PMID: 40075801 PMCID: PMC11898410 DOI: 10.3390/diagnostics15050554] [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: 12/28/2024] [Revised: 01/22/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background and Objectives: We conducted a retrospective observational study to evaluate the impact of elevated blood glucose levels in patients with SARS-CoV-2 infection and a prior diagnosis of diabetes mellitus (DM) or newly diagnosed hyperglycemia. Materials and Methods: This study analyzed 6065 patients admitted to the COVID-19 departments of the "Marius Nasta" National Institute of Pulmonology in Bucharest, Romania, between 26 October 2020 and 5 January 2023. Of these, 813 patients (13.40%) were selected for analysis due to either a pre-existing diagnosis of DM or hyperglycemia at the time of hospital admission. Results: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated in patients with blood glucose levels exceeding 300 mg/dL. These elevations correlated with the presence of respiratory failure and increased mortality rates. Additionally, oxygen requirements were significantly higher at elevated blood glucose levels (p < 0.001), with a direct relationship between glycemia and oxygen demand. This was accompanied by lower oxygen saturation levels (p < 0.001). Maximum blood glucose levels were associated with the severity of respiratory failure (AUC 0.6, 95% CI: 0.56-0.63, p < 0.001). We identified cut-off values for blood glucose at admission (217.5 mg/dL) and maximum blood glucose during hospitalization (257.5 mg/dL), both of which were associated with disease severity and identified as risk factors for increased mortality. Conclusions: High blood glucose levels, both at admission and during hospitalization, were identified as risk factors for poor prognosis and increased mortality in patients with SARS-CoV-2 infection, regardless of whether the hyperglycemia was due to a prior diagnosis of DM or was newly developed during the hospital stay. These findings underscore the importance of glycemic control in the management of hospitalized COVID-19 patients.
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Affiliation(s)
- Oana-Andreea Parlițeanu
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
| | - Mara-Amalia Bălteanu
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
| | - Dragoș Cosmin Zaharia
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Tudor Constantinescu
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Alexandra Maria Cristea
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Ștefan Dumitrache-Rujinscki
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Andra Elena Nica
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Cristiana Voineag
- Department of Diabetes, Universitatea Dunărea de Jos, 800201 Galați, Romania; (C.V.); (O.S.A.)
| | - Octavian Sabin Alexe
- Department of Diabetes, Universitatea Dunărea de Jos, 800201 Galați, Romania; (C.V.); (O.S.A.)
| | - Emilia Tabacu
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Alina Croitoru
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Irina Strâmbu
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
| | - Roxana Maria Nemeș
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
| | - Beatrice Mahler
- Institutul Național de Pneumoftizologie Marius Nasta, 050159 București, Romania; (O.-A.P.); (D.C.Z.); (T.C.); (A.M.C.); (Ș.D.-R.); (E.T.); (A.C.); (I.S.); (R.M.N.); (B.M.)
- Department of Pneumology, Universitatea de Medicină și Farmacie Carol Davila, 050474 Bucrești, Romania;
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Yada N, Zhang Q, Bignotti A, Ye Z, Zheng XL. ADAMTS13 or Caplacizumab Reduces the Accumulation of Neutrophil Extracellular Traps and Thrombus in Whole Blood of COVID-19 Patients under Flow. Thromb Haemost 2024; 124:725-738. [PMID: 38272066 PMCID: PMC11260255 DOI: 10.1055/a-2253-9359] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
BACKGROUND Neutrophil NETosis and neutrophil extracellular traps (NETs) play a critical role in pathogenesis of coronavirus disease 2019 (COVID-19)-associated thrombosis. However, the extents and reserve of NETosis, and potential of thrombus formation under shear in whole blood of patients with COVID-19 are not fully elucidated. Neither has the role of recombinant ADAMTS13 or caplacizumab on the accumulation of NETs and thrombus in COVID-19 patients' whole blood under shear been investigated. METHODS Flow cytometry and microfluidic assay, as well as immunoassays, were employed for the study. RESULTS We demonstrated that the percentage of H3Cit + MPO+ neutrophils, indicative of NETosis, was dramatically increased in patients with severe but not critical COVID-19 compared with that in asymptomatic or mild disease controls. Upon stimulation with poly [I:C], a double strain DNA mimicking viral infection, or bacterial shigatoxin-2, the percentage of H3Cit + MPO+ neutrophils was not significantly increased in the whole blood of severe and critical COVID-19 patients compared with that of asymptomatic controls, suggesting the reduction in NETosis reserve in these patients. Microfluidic assay demonstrated that the accumulation of NETs and thrombus was significantly enhanced in the whole blood of severe/critical COVID-19 patients compared with that of asymptomatic controls. Like DNase I, recombinant ADAMTS13 or caplacizumab dramatically reduced the NETs accumulation and thrombus formation under arterial shear. CONCLUSION Significantly increased neutrophil NETosis, reduced NETosis reserve, and enhanced thrombus formation under arterial shear may play a crucial role in the pathogenesis of COVID-19-associated coagulopathy. Recombinant ADAMTS13 or caplacizumab may be explored for the treatment of COVID-19-associated thrombosis.
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Affiliation(s)
- Noritaka Yada
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kanas City, Kansas, United States
| | - Quan Zhang
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kanas City, Kansas, United States
| | - Antonia Bignotti
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kanas City, Kansas, United States
| | - Zhan Ye
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kanas City, Kansas, United States
| | - X. Long Zheng
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kanas City, Kansas, United States
- Institute of Reproductive Medicine and Developmental Sciences, The University of Kansas Medical Center, Kanas City, Kansas, United States
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Jahagirdar P, Vaishnav K, Sarathy NA, Singh H, Kumia K, Banerjee A. Role of C-reactive protein, IL-6, and D-dimers in prediction of severity of coronavirus disease 2019: A pilot study. J Oral Maxillofac Pathol 2024; 28:205-210. [PMID: 39157833 PMCID: PMC11329092 DOI: 10.4103/jomfp.jomfp_28_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] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/17/2024] [Accepted: 03/29/2024] [Indexed: 08/20/2024] Open
Abstract
Background The global outbreak of coronavirus disease 2019 (COVID-19) presents numerous obstacles for healthcare professionals. The present study aimed to evaluate and compare the role of serum biomarkers like- C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimers in the severity of COVID-19 infection. Methodology A cross-sectional, observational retrospective pilot study was conducted in Udaipur, Rajasthan, wherein data was collected from 250 subjects, out of which, data of 100 subjects were included as per the inclusion criteria. The data was recorded retrospectively among the health professionals via Google Forms in Udaipur, Rajasthan. Results There were 1 (1%), 3 (3%), 31 (31%) and 65 (65%) participants with minor elevation (0.3-1.0), moderate elevation (1-10), marked elevation (10-50) and severe elevation (>50) of CRP respectively. The difference between the groups was statistically highly significant with a significantly higher number of study participants with a severe elevation of CRP levels (χ2 = 107.84, P < 0.001). The results showed that there was a significant difference between the groups with IL6 in 0-7 range while 96 (96%) study participants had >7 IL6, and the difference was statistically highly significant (2 = 84.640, P 0.001). Conclusion In conclusion, the existing body of research indicates a discernible correlation between COVID-19 infection and the fluctuation of biomarker levels. This supplement has the potential to be utilised in clinical practice as a means of informing treatment decisions and determining the necessity of admission to the intensive care unit (ICU).
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Affiliation(s)
- Pramod Jahagirdar
- Department of Dentistry, Karnavati School of Research, Gandhinagar, Gujarat, India
| | - Kalpesh Vaishnav
- Department of Prosthodontics, Crown, and Bridge, Karnavati School of Dentistry, Gujarat, India
| | - Niharika Abhay Sarathy
- Department of Oral and Maxillofacial Pathology, R.R. Dental College and Hospital, Udaipur, Rajasthan, India
| | - Harneet Singh
- Department of Oral Medicine and Radiology, Post Graduate Institute of Dental Sciences, Rohtak, Haryana, India
| | - Komal Kumia
- Department of Oral Medicine and Radiology, Post Graduate Institute of Dental Sciences, Rohtak, Haryana, India
| | - Abhishek Banerjee
- Department of Oral and Maxillofacial Pathology, Awadh Dental College and Hospital, Jamshedpur, Jharkhand, India
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Khaleq MAA. Effect of Enoxaparin on D-dimer levels in hospitalized Corona Virus patients with a comparison of its level in patients with comorbid conditions. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:828-833. [PMID: 38865643 DOI: 10.36740/wlek202404131] [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: 06/14/2024]
Abstract
OBJECTIVE Aim: The main goal is to assess the levels of comorbid diseases and examine the changes in D-dimer in hospitalized patients before and following SC enoxaparin medication. PATIENTS AND METHODS Material and Methods: At the Al-Yarmouk Teaching Hospital in Baghdad, Iraq, from October 2022 to May 2023, 86 patients who were hospitalized and had severe to critical COVID-19 infections provided data for a retrospective analysis. RESULTS Results: The medical records of all COVID-19 patients who were hospitalized and whose D-dimer level was greater than 0.5 mg/l and who were given enoxaparin (40 mg subcutaneously) were reviewed with the requisite authorization from the relevant authorities. The D-dimer level was assessed following therapy on the day of admission and day five after commencing enoxaparin. An examination of 86 case records revealed that persons with COVID-19 had significantly decreased D-dimer levels after taking subcutaneous enoxaparin (p-value<0.0001). The comorbidities (diabetes mellitus, hypertension) of patients who received the drug were compared. CONCLUSION Conclusions: Enoxaparin and other anticoagulants were utilized to treat the coagulopathy brought on by COVID-19. Low molecular weight heparin enoxaparin has demonstrated positive outcomes in the management of VTE. A decrease in D-dimer level is anticipated when COVID-19 patients are treated with subcutaneous enoxaparin, partly because decreased coagulation results in lower fibrin formation.
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Zhang Q, Bignotti A, Yada N, Ye Z, Liu S, Han Z, Zheng XL. Dynamic Assessment of Plasma von Willebrand Factor and ADAMTS13 Predicts Mortality in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Med 2023; 12:7174. [PMID: 38002786 PMCID: PMC10672082 DOI: 10.3390/jcm12227174] [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: 10/26/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Plasma levels of von Willebrand factor (VWF) are significantly elevated in patients with coronavirus disease 2019 (COVID-19). However, dynamic changes and prognostic value of this biomarker in hospitalized patients with COVID-19 have not been determined. METHODS A total of 124 patients infected with SARS-CoV-2 were prospectively recruited for the study. Serial blood samples were obtained at the time of admission (D1), 3-4 days following standard-care treatments (D2), and 1-2 days prior to discharge or any time collected prior to death (D3). Plasma VWF antigen, ADAMTS13 antigen, and ADAMTS13 proteolytic activity, as well as the ratio of VWF/ADAMTS13 were determined, followed by various statistical analyses. RESULTS On admission, plasma levels of VWF in COVID-19 patients were significantly elevated compared with those in the healthy controls, but no statistical significance was detected among patients with different disease severity. Plasma ADAMTS13 activity but not its antigen levels were significantly lower in patients with severe or critical COVID-19 compared with that in other patient groups. Interestingly, the ratios of plasma VWF antigen to ADAMTS13 antigen were significantly higher in patients with severe or critical COVID-19 than in those with mild to moderate disease. More importantly, plasma levels of VWF and the ratios of VWF/ADAMTS13 were persistently elevated in patients with COVID-19 throughout hospitalization. Kaplan-Meier and Cox proportional hazard regression analyses demonstrated that an increased plasma level of VWF or ratio of VWF/ADAMTS13 at D2 and D3 was associated with an increased mortality rate. CONCLUSIONS Persistent endotheliopathy, marked by the elevated levels of plasma VWF or VWF/ADAMTS13 ratio, is present in all hospitalized patients following SARS-CoV-2 infection, which is strongly associated with mortality.
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Affiliation(s)
- Quan Zhang
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Antonia Bignotti
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Noritaka Yada
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Zhan Ye
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Szumam Liu
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Zhe Han
- Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Baltimore, MD 21201, USA
| | - X. Long Zheng
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
- Institute of Reproductive and Developmental Sciences, The University of Kansas Medical Center, Kansas City, KS 66160, USA
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Feltrin TD, Cielo CA, Pasqualoto AS. Relation between Orotracheal Intubation, Inflammatory Markers, Breathing and Voice in Post-COVID-19. J Voice 2023:S0892-1997(23)00070-X. [PMID: 37045738 PMCID: PMC9946891 DOI: 10.1016/j.jvoice.2023.02.015] [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: 12/20/2022] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/25/2023]
Abstract
INTRODUCTION COVID-19, an infectious disease with a wide spectrum of clinical manifestations and intensities in the human body, it can cause respiratory and vocal disorders, with fatigue. OBJECTIVE To verify the relation between biological Inflammatory markers D-dimers and C-Reactive Protein, Forced Vital Capacity, Maximum Phonation Time, vocal performance and fatigue, length of hospitalization period and gender of people affected by COVID-19 who were hospitalized, but did not use orotracheal intubation and compare with a group of post-COVID-19 patients with orotracheal intubation. METHODS Data on D-dimers and C-Reactive Protein, spirometry, Maximum Phonation Time, performance and vocal fatigue were collected. The study included 42 adult people affected by COVID-19 who were hospitalized, 22 (52.4%) female and 20 (47.6%) male; 23 (54.8%) critical cases composing the group with orotracheal intubation (average age 48.9 years old) and 19 (45.24%) severe cases in the group without orotracheal intubation (average age 49.9 years old). RESULTS hospital length of stay was significantly longer for the group with orotracheal intubation; D-dimers were significantly altered in all groups; correlations between maximum phonation times were positive and significant; correlations between maximum phonation times, vocal performance and fatigue were both negative and significant. CONCLUSION Patients with orotracheal intubation had longer hospital internment and increased D-dimers and were amazed that, whenever maximum phonation times decreased performance and vocal fatigue increased.
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Affiliation(s)
- Thaís D Feltrin
- Department of Speech Therapy, Federal University of Santa Maria, Santa Maria, RS, Brazil.
| | - Carla A Cielo
- Department of Speech Therapy and Human Communication Disorders, Federal University of Santa Maria, Santa Maria RS, Brazil
| | - Adriane S Pasqualoto
- Department of Physiotherapy and Human Communication Disorders, Federal University of Santa Maria, Santa Maria, RS, Brazil
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Sanjay S, Bhakti Mistra S, Patro SK, Kawali A, Shetty R, Mahendradas P. Systemic Markers in Ophthalmic Manifestations of Post Corona Virus Disease-19 (COVID-19). Ocul Immunol Inflamm 2023; 31:410-415. [PMID: 35138993 DOI: 10.1080/09273948.2021.2025253] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Corona virus disease (COVID-19) has been associated with ophthalmic manifestations which can occur during or following the infection. PURPOSE To explore the systemic status in ophthalmic patients who had a recent history of COVID-19 or those with positive COVID-19 antibody status. METHODS Retrospective case series. RESULTS 30 patients with history of COVID-19 infection and positive COVID-19 antibodies were included in the study. The median age was 49 years (mean 48.7 ± 13.7 years), 20 were males (66.7%) and 10 (33.3%) were females. Patients with VA>/= 6/60 were included in group 1 and those with VA<6/60 were included in group 2. D-dimer/serum Ferritin levels were raised in group 2 compared to group 1with (p=0.013)/(p=0.018) respectively. CONCLUSION Serum D-dimer and ferritin levels were statistically significant and were higher in patients with sight threatening ocular manifestations. ESR and CRP were raised even after recovery from COVID-19 although they were not statistically significant.
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Affiliation(s)
- Srinivasan Sanjay
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Sai Bhakti Mistra
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Sithun Kumar Patro
- Department of Community Medicine, MKCG Medical College, Brahmapur, India
| | - Ankush Kawali
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Rohit Shetty
- Department of Neuro-ophthalmology, Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India
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Swisher JW, Weaver E. The Evolving Management and Treatment Options for Patients with Pulmonary Hypertension: Current Evidence and Challenges. Vasc Health Risk Manag 2023; 19:103-126. [PMID: 36895278 PMCID: PMC9990521 DOI: 10.2147/vhrm.s321025] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 02/01/2023] [Indexed: 03/06/2023] Open
Abstract
Pulmonary hypertension may develop as a disease process specific to pulmonary arteries with no identifiable cause or may occur in relation to other cardiopulmonary and systemic illnesses. The World Health Organization (WHO) classifies pulmonary hypertensive diseases on the basis of primary mechanisms causing increased pulmonary vascular resistance. Effective management of pulmonary hypertension begins with accurately diagnosing and classifying the disease in order to determine appropriate treatment. Pulmonary arterial hypertension (PAH) is a particularly challenging form of pulmonary hypertension as it involves a progressive, hyperproliferative arterial process that leads to right heart failure and death if untreated. Over the last two decades, our understanding of the pathobiology and genetics behind PAH has evolved and led to the development of several targeted disease modifiers that ameliorate hemodynamics and quality of life. Effective risk management strategies and more aggressive treatment protocols have also allowed better outcomes for patients with PAH. For those patients who experience progressive PAH with medical therapy, lung transplantation remains a life-saving option. More recent work has been directed at developing effective treatment strategies for other forms of pulmonary hypertension, such as chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary hypertension due to other lung or heart diseases. The discovery of new disease pathways and modifiers affecting the pulmonary circulation is an ongoing area of intense investigation.
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Affiliation(s)
- John W Swisher
- East Tennessee Pulmonary Hypertension Center, StatCare Pulmonary Consultants, Knoxville, TN, USA
| | - Eric Weaver
- East Tennessee Pulmonary Hypertension Center, StatCare Pulmonary Consultants, Knoxville, TN, USA
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Farhana A, Tantry BA, Shah NN, Bandy A, Nabi M, Khursheed SQ, Shahnawaz M, Mustafa H. Clinical characteristics among patients with COVID‑19: A single‑center retrospective study. Biomed Rep 2022; 17:94. [PMID: 36382262 PMCID: PMC9634048 DOI: 10.3892/br.2022.1577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 09/29/2022] [Indexed: 06/16/2023] Open
Abstract
The aim of the present study was to investigate the clinical features and laboratory parameters of hospitalized patients with coronavirus disease 2019 (COVID-19) and assess the characteristics between severe and non-severe cases. The study retrospectively analyzed the clinical data of 1,096 patients, of which, 626 (57.11%) and 470 (42.89%) were categorized into severe and non-severe groups, respectively. Clinical parameters such as signs and symptoms, comorbidities, levels of D-dimer, C-reactive protein (CRP), interleukin 6 (IL-6) and lactate dehydrogenase were analyzed. The data are presented as frequencies, means and standard deviations. The chi-square test and Mann-Whitney U test were used to assess any significant differences between the severe and non-severe COVID-19 groups. The clinical symptoms in severe COVID-19 cases included anosmia (P≤0.01), sore throat (P≤0.01), fatigue (P≤0.01), headache (P≤0.01), and shortness of breath (P≤0.01). Laboratory findings showed a significant increase in CRP (21.90±40.23 vs. 16.13±21.82; P≤0.01) and IL-6 levels (58.92±55.07 vs. 41.41±38.30; P≤0.01). Patients with severe COVID-19 had significant lymphopenia compared with that in non-severe cases. Among the comorbidities, hypertension (P≤0.01) was significantly more frequent in patients with severe COVID-19. In conclusion, major derangements in laboratory parameters were observed in patients with severe COVID-19 infection.
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Affiliation(s)
- Anjum Farhana
- Department of Microbiology, Government Medical College, Srinagar, Jammu and Kashmir 190010, India
| | - Bilal Ahmad Tantry
- Department of Microbiology, Government Medical College, Srinagar, Jammu and Kashmir 190010, India
| | - Naveed Nazir Shah
- Department of Pulmonary Medicine, Chest Disease Hospital, Government Medical College, Drugjan, Srinagar, Jammu and Kashmir 190001, India
| | - Altaf Bandy
- Department of Family and Community Medicine, College of Medicine, Jouf University, Sakaka, Al Jouf 70214, Kingdom of Saudi Arabia
| | - Mudasar Nabi
- Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir 190010, India
| | | | - Mir Shahnawaz
- Department of Respiratory Medicine, Chest Disease Hospital, Government Medical College, Drugjan, Srinagar, Jammu and Kashmir 190010, India
| | - Hena Mustafa
- Department of Respiratory Medicine, Chest Disease Hospital, Government Medical College, Drugjan, Srinagar, Jammu and Kashmir 190010, India
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Abstract
Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.
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Woller SC, de Wit K, Robert‐Ebadi H, Masias C, Klok FA, den Exter PL, Morange P, Castelli D, Hansen J. A systematic review of biomarkers among hospitalized patients with COVID-19 predictive of venous thromboembolism: A communication from the Predictive and Diagnostic Variables Scientific and Standardization Committee of the ISTH. Res Pract Thromb Haemost 2022; 6:e12786. [PMID: 36032214 PMCID: PMC9412137 DOI: 10.1002/rth2.12786] [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] [Received: 03/04/2022] [Revised: 07/19/2022] [Accepted: 07/20/2022] [Indexed: 12/15/2022] Open
Abstract
Background Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures.
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Affiliation(s)
- Scott C. Woller
- Department of MedicineIntermountain Medical Center, Intermountain HealthcareMurrayUtahUSA
- Department of Internal MedicineUniversity of Utah School of MedicineSalt Lake CityUtahUSA
| | - Kerstin de Wit
- Departments of Emergency Medicine and MedicineQueen's UniversityKingstonOntarioCanada
- Departments of Medicine and HEIMcMaster UniversityHamiltonOntarioCanada
| | - Helia Robert‐Ebadi
- Division of Angiology and HemostasisGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
| | - Camila Masias
- Florida International University ‐ Herbert Wertheim College of MedicineMiamiFloridaUSA
| | - Frederikus A. Klok
- Department of Medicine – Thrombosis and HemostasisLeiden University Medical CenterLeidenThe Netherlands
| | - Paul L. den Exter
- Department of Medicine – Thrombosis and HemostasisLeiden University Medical CenterLeidenThe Netherlands
| | - Pierre‐Emmanuel Morange
- Aix Marseille UnivMarseilleFrance
- Hematology DepartmentLa Timone University Hospital of MarseilleMarseilleFrance
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12
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Woller SC, Stevens SM, Bledsoe JR, Fazili M, Lloyd JF, Snow GL, Horne BD. Biomarker derived risk scores predict venous thromboembolism and major bleeding among patients with COVID-19. Res Pract Thromb Haemost 2022; 6:e12765. [PMID: 35873221 PMCID: PMC9301476 DOI: 10.1002/rth2.12765] [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] [Received: 11/30/2021] [Revised: 05/21/2022] [Accepted: 06/19/2022] [Indexed: 12/15/2022] Open
Abstract
Background Venous thromboembolism (VTE) risk is increased in patients with COVID-19 infection. Understanding which patients are likely to develop VTE may inform pharmacologic VTE prophylaxis decision making. The hospital-associated venous thromboembolism-Intermountain Risk Score (HA-VTE IMRS) and the hospital-associated major bleeding-Intermountain Risk Score (HA-MB IMRS) are risk scores predictive of VTE and bleeding that were derived from only patient age and data found in the complete blood count (CBC) and basic metabolic panel (BMP). Objectives We assessed the HA-VTE IMRS and HA-MB IMRS for predictiveness of 90-day VTE and major bleeding, respectively, among patients diagnosed with COVID-19, and further investigated if adding D-dimer improved these predictions. We also reported 30-day outcomes. Patients/Methods We identified 5047 sequential patients with a laboratory confirmed diagnosis of COVID-19 and a CBC and BMP between 2 days before and 7 days following the diagnosis of COVID-19 from March 12, 2020, to February 28, 2021. We calculated the HA-VTE IMRS and the HA-MB IMRS for all patients. We assessed the added predictiveness of D-dimer obtained within 48 hours of the COVID test. Results The HA-VTE IMRS yielded a c-statistic of 0.70 for predicting 90-day VTE and adding D-dimer improved the c-statistic to 0.764 with the corollary sensitivity/specificity/positive/negative predictive values of 49.4%/75.7%/6.7%/97.7% and 58.8%/76.2%/10.9%/97.4%, respectively. Among hospitalized and ambulatory patients separately, the HA-VTE IMRS performed similarly. The HA-MB IMRS predictiveness for 90-day major bleeding yielded a c-statistic of 0.64. Conclusion The HA-VTE IMRS and HA-MB IMRS predict 90- and 30-day VTE and major bleeding among COVID-19 patients. Adding D-dimer improved the predictiveness of the HA-VTE IMRS for VTE.
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Affiliation(s)
- Scott C. Woller
- Department of MedicineIntermountain Medical Center, Intermountain HealthcareMurrayUtahUSA
- Department of Internal MedicineUniversity of Utah School of MedicineSalt Lake CityUtahUSA
| | - Scott M. Stevens
- Department of MedicineIntermountain Medical Center, Intermountain HealthcareMurrayUtahUSA
- Department of Internal MedicineUniversity of Utah School of MedicineSalt Lake CityUtahUSA
| | - Joseph R. Bledsoe
- Department of Emergency Medicine, Intermountain Medical CenterIntermountain HealthcareMurrayUtahUSA
- Stanford UniversityStanfordCaliforniaUSA
| | - Masarret Fazili
- Department of MedicineIntermountain Medical Center, Intermountain HealthcareMurrayUtahUSA
| | - James F. Lloyd
- Department of InformaticsIntermountain Medical Center, Intermountain HealthcareMurrayUtahUSA
| | - Greg L. Snow
- Intermountain Statistical Data Center, Intermountain Medical CenterIntermountain HealthcareMurrayUtahUSA
| | - Benjamin D. Horne
- Intermountain Medical Center Heart InstituteMurrayUtahUSA
- Division of Cardiovascular MedicineStanford UniversityStanfordCaliforniaUSA
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13
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Ma S, Su W, Sun C, Lowe S, Zhou Z, Liu H, Qu G, Xia W, Xie P, Wu B, Gao J, Feng L, Sun Y. Does aspirin have an effect on risk of death in patients with COVID-19? A meta-analysis. Eur J Clin Pharmacol 2022; 78:1403-1420. [PMID: 35732963 PMCID: PMC9217117 DOI: 10.1007/s00228-022-03356-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/14/2022] [Indexed: 01/06/2023]
Abstract
Purpose The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality. Methods A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed. Results The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50–0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48–0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52–0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52–0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80–1.87; P = 0.96). Conclusions This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding. Supplementary information The online version contains supplementary material available at 10.1007/s00228-022-03356-5.
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Affiliation(s)
- Shaodi Ma
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Wanying Su
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA
| | - Scott Lowe
- College of Osteopathic Medicine, Kansas City University, 1750 Independence Ave, Kansas City, MO, 64106, USA
| | - Zhen Zhou
- Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia
| | - Haixia Liu
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Guangbo Qu
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Weihang Xia
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Peng Xie
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Birong Wu
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Juan Gao
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Linya Feng
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China
| | - Yehuan Sun
- Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China.
- Chaohu Hospital, Anhui Medical University, No. 64 Chaohubei Road, Anhui, 238000, China.
- Center for Evidence-Based Practice, Anhui Medical University, No. 81 Meishan Road, Anhui, 230032, China.
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14
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Pawar A, Russo M, Rani I, Goswami K, Russo GL, Pal A. A critical evaluation of risk to reward ratio of quercetin supplementation for COVID-19 and associated comorbid conditions. Phytother Res 2022; 36:2394-2415. [PMID: 35393674 PMCID: PMC9111035 DOI: 10.1002/ptr.7461] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 03/19/2022] [Accepted: 03/26/2022] [Indexed: 01/08/2023]
Abstract
The interim results of the large, multinational trials on coronavirus disease 2019 (COVID‐19) using a combination of antiviral drugs appear to have little to no effect on the 28‐day mortality or the in‐hospital course. Therefore, there is a still vivid interest in finding alternate re‐purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin's possible therapeutic/prophylaxis efficacy against severe acute respiratory syndrome coronavirus (SARS‐CoV) as well as comorbidities like chronic obstructive pulmonary disease (COPD), diabetes mellitus, obesity, coagulopathy, and hypertension. Currently, 14 interventional clinical trials are underway assessing the efficacy of quercetin along with other antiviral drugs/nutritional supplements as prophylaxis/treatment option against COVID‐19. The present review is tempting to suggest that, based on circumstantial scientific evidence and preliminary clinical data, the flavonoid quercetin can ameliorate COVID‐19 infection and symptoms acting in concert on two parallel and independent paths: inhibiting key factors responsible for SARS‐CoV‐2 infections and mitigating the clinical manifestations of the disease in patients with comorbid conditions. Despite the broad therapeutic properties of quercetin, further high power randomized clinical trials are needed to firmly establish its clinical efficacy against COVID‐19.
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Affiliation(s)
- Anil Pawar
- Department of Zoology, DAV University, Jalandhar, India
| | - Maria Russo
- National Research Council, Institute of Food Sciences, Avellino, Italy
| | - Isha Rani
- Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Ambala, India
| | | | - Gian Luigi Russo
- National Research Council, Institute of Food Sciences, Avellino, Italy
| | - Amit Pal
- Department of Biochemistry, AIIMS, Kalyani, India
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15
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Gogtay M, Singh Y, Bullappa A, Scott J. Retrospective analysis of aspirin's role in the severity of COVID-19 pneumonia. World J Crit Care Med 2022; 11:92-101. [PMID: 35433312 PMCID: PMC8968479 DOI: 10.5492/wjccm.v11.i2.92] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/03/2022] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Since December 2019, an outbreak of pneumonia caused by severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) has led to a life-threatening ongoing pandemic worldwide. A retrospective study by Chow et al showed aspirin use was associated with decreased intensive care unit (ICU) admissions in hospitalized coronavirus disease 2019 (COVID-19) patients. Recently, the RECOVERY TRIAL showed no associated reductions in the 28-d mortality or the progression to mechanical ventilation of such patients. With these conflicting findings, our study was aimed at evaluating the impact of daily aspirin intake on the outcome of COVID-19 patients.
AIM To study was aimed at evaluating the impact of daily aspirin intake on the outcome of COVID-19 patients.
METHODS This retrospective cohort study was conducted on 125 COVID-19 positive patients. Subgroup analysis to evaluate the association of demographics and comorbidities was undertaken. The impact of chronic aspirin use was assessed on the survival outcomes, need for mechanical ventilation, and progression to ICU. Variables were evaluated using the chi-square test and multinomial logistic regression analysis.
RESULTS 125 patients were studied, 30.40% were on daily aspirin, and 69.60% were not. Cross-tabulation of the clinical parameters showed that hypertension (P = 0.004), hyperlipidemia (0.016), and diabetes mellitus (P = 0.022) were significantly associated with aspirin intake. Regression analysis for progression to the ICU, need for mechanical ventilation and survival outcomes against daily aspirin intake showed no statistical significance.
CONCLUSION Our study suggests that daily aspirin intake has no protective impact on COVID-19 illness-associated survival outcomes, mechanical ventilation, or progression to ICU level of care.
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Affiliation(s)
- Maya Gogtay
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01604, United States
| | - Yuvaraj Singh
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01604, United States
| | - Asha Bullappa
- Community Medicine and Biostatistics, SS Institute of Medical Sciences, Davangere 577003, Karnataka, India
| | - Jeffrey Scott
- Department of Critical Care Medicine and Pulmonology, Reliant medical group- Saint Vincent Hospital, Worcester, MA 01604, United States
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16
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Perico L, Morigi M, Galbusera M, Pezzotta A, Gastoldi S, Imberti B, Perna A, Ruggenenti P, Donadelli R, Benigni A, Remuzzi G. SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and Complement System Leading to Platelet Aggregation. Front Immunol 2022; 13:827146. [PMID: 35320941 PMCID: PMC8936079 DOI: 10.3389/fimmu.2022.827146] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cells, it has been poorly investigated whether, in the complexity of viral infection in the human host, specific viral elements alone can induce endothelial damage. Detection of circulating spike protein in the sera of severe COVID-19 patients was evaluated by ELISA. In vitro experiments were performed on human microvascular endothelial cells from the derma and lung exposed to SARS-CoV-2-derived spike protein 1 (S1). The expression of adhesive molecules was studied by immunofluorescence and leukocyte adhesion and platelet aggregation were assessed under flow conditions. Angiotensin converting enzyme 2 (ACE2) and AMPK expression were investigated by Western Blot analysis. In addition, S1-treated endothelial cells were incubated with anti-ACE2 blocking antibody, AMPK agonist, or complement inhibitors. Our results show that significant levels of spike protein were found in the 30.4% of severe COVID-19 patients. In vitro, the activation of endothelial cells with S1 protein, via ACE2, impaired AMPK signalling, leading to robust leukocyte recruitment due to increased adhesive molecule expression and thrombomodulin loss. This S1-induced pro-inflammatory phenotype led to exuberant C3 and C5b-9 deposition on endothelial cells, along with C3a and C5a generation that further amplified S1-induced complement activation. Functional blockade of ACE2 or complement inhibition halted S1-induced platelet aggregates by limiting von Willebrand factor and P-selectin exocytosis and expression on endothelial cells. Overall, we demonstrate that SARS-CoV-2-derived S1 is sufficient in itself to propagate inflammatory and thrombogenic processes in the microvasculature, amplified by the complement system, recapitulating the thromboembolic complications of COVID-19.
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Affiliation(s)
- Luca Perico
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Marina Morigi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Miriam Galbusera
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Anna Pezzotta
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Sara Gastoldi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Barbara Imberti
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Annalisa Perna
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Piero Ruggenenti
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
- Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
| | - Roberta Donadelli
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Ariela Benigni
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
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17
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Hattori Y, Hattori K, Machida T, Matsuda N. Vascular endotheliitis associated with infections: Its pathogenetic role and therapeutic implication. Biochem Pharmacol 2022; 197:114909. [PMID: 35021044 PMCID: PMC8743392 DOI: 10.1016/j.bcp.2022.114909] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 12/20/2022]
Abstract
Vascular endothelial cells are major participants in and regulators of immune responses and inflammation. Vascular endotheliitis is regarded as a host immune-inflammatory response of the endothelium forming the inner surface of blood vessels in association with a direct consequence of infectious pathogen invasion. Vascular endotheliitis and consequent endothelial dysfunction can be a principle determinant of microvascular failure, which would favor impaired perfusion, tissue hypoxia, and subsequent organ failure. Emerging evidence suggests the role of vascular endotheliitis in the pathogenesis of coronavirus disease 2019 (COVID-19) and its related complications. Thus, once initiated, vascular endotheliitis and resultant cytokine storm cause systemic hyperinflammation and a thrombotic phenomenon in COVID-19, leading to acute respiratory distress syndrome and widespread organ damage. Vascular endotheliitis also appears to be a contributory factor to vasculopathy and coagulopathy in sepsis that is defined as life-threatening organ dysfunction due to a dysregulated response of the host to infection. Therefore, protecting endothelial cells and reversing vascular endotheliitis may be a leading therapeutic goal for these diseases associated with vascular endotheliitis. In this review, we outline the etiological and pathogenic importance of vascular endotheliitis in infection-related inflammatory diseases, including COVID-19, and possible mechanisms leading to vascular endotheliitis. We also discuss pharmacological agents which may be now considered as potential endotheliitis-based treatment modalities for those diseases.
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Affiliation(s)
- Yuichi Hattori
- Advanced Research Promotion Center, Health Sciences University of Hokkaido, Tobetsu, Japan; Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
| | - Kohshi Hattori
- Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo, Japan
| | - Takuji Machida
- Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Japan
| | - Naoyuki Matsuda
- Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
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18
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Atıcı SD, Akpınar G. Splenic infarct in a COVID-19 patient under anticoagulant therapy with normal D-dimer levels. Int J Surg Case Rep 2022; 92:106847. [PMID: 35194547 PMCID: PMC8855613 DOI: 10.1016/j.ijscr.2022.106847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 01/23/2022] [Accepted: 02/15/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Many studies have shown that COVID-19 can progress with coagulopathy and multisystemic thrombotic events. We report a patient who presented with abdominal pain after COVID-19 and was found to have splenic infarction (SI) concomitant with acute myocardial infarctus (MI) under anticoagulant treatment. CASE PRESENTATION A 45-year-old man was admitted to the emergency department with left-sided abdominal pain radiating through to his back persisting for one day. He had COVID-19 PCR positivity nine days ago. After seven days of hospitalization due to COVID-19 pneumonia, he had been discharged with low-molecular-weight heparin (LMWH). Abdominal computerized tomography (CT) showed SI. His ECG and laboratory parameters were normal except for 17.2 × 10∧3/μL leukocytosis. The anticoagulant drug dose that he was taking was increased to 2 × 0.6 mL during hospitalization. He described new-onset chest pain during follow-up. Acute anterior MI was detected on ECG. Successful percutaneous coronary angiography was performed by cardiologists. No problems were observed in the follow-up. The patient was discharged on the fifth day of conservative treatment due to splenic infarction. CONCLUSION Thrombosis prophylaxis with prophylactic doses of LMWH in hospitalized COVID-19 patients may not be sufficient to prevent the development of coagulopathy in patients. Abdominal-visceral thromboembolism should be suspected in a COVID-19-positive patient presenting with abdominal pain despite receiving anticoagulant therapy and normal d-dimer levels.
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Affiliation(s)
- Semra Demirli Atıcı
- University of Health Sciences Tepecik Training and Research Hospital, Department of General Surgery, Turkey.
| | - Göksever Akpınar
- University of Health Sciences Tepecik Training and Research Hospital, Department of General Surgery, Turkey
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19
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Zamboni P, Bortolotti D, Occhionorelli S, Traina L, Neri LM, Rizzo R, Gafà R, Passaro A. Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab. J Intern Med 2022; 291:224-231. [PMID: 34437741 PMCID: PMC8662187 DOI: 10.1111/joim.13385] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.
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Affiliation(s)
- Paolo Zamboni
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy.,Department of Surgery, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
| | - Daria Bortolotti
- Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy
| | - Savino Occhionorelli
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy.,Department of Surgery, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
| | - Luca Traina
- Department of Surgery, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
| | - Luca Maria Neri
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Roberta Rizzo
- Department of Surgery, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
| | - Roberta Gafà
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy.,Oncological and Medical Department, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
| | - Angelina Passaro
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy.,Medical Department, University Hospital of Ferrara Arcispedale Sant'Anna, Ferrara, Italy
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20
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Batta Y, King C, Johnson J, Haddad N, Boueri M, Haddad G. Sequelae and Comorbidities of COVID-19 Manifestations on the Cardiac and the Vascular Systems. Front Physiol 2022; 12:748972. [PMID: 35095546 PMCID: PMC8795698 DOI: 10.3389/fphys.2021.748972] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 10/28/2021] [Indexed: 01/08/2023] Open
Abstract
COVID-19 patients with pre-existing cardiovascular conditions are at greater risk of severe illness due to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. This review evaluates the highest risk factors for these patients, not limited to pre-existing hypertension, cardiac arrhythmias, hypercoagulation, ischemic heart disease, and a history of underlying heart conditions. SARS-CoV-2 may also precipitate de novo cardiac complications. The interplay between existing cardiac conditions and de novo cardiac complications is the focus of this review. In particular, SARS-CoV-2 patients present with hypercoagulation conditions, cardiac arrhythmias, as significant complications. Also, cardiac arrhythmias are another well-known cardiovascular-related complication seen in COVID-19 infections and merit discussion in this review. Amid the pandemic, myocardial infarction (MI) has been reported to a high degree in SARS-CoV-2 patients. Currently, the specific causative mechanism of the increased incidence of MI is unclear. However, studies suggest several links to high angiotensin-converting enzyme 2 (ACE2) expression in myocardial and endothelial cells, systemic hyper-inflammation, an imbalance between myocardial oxygen supply and demand, and loss of ACE2-mediated cardio-protection. Furthermore, hypertension and SARS-CoV-2 infection patients' prognosis has shown mixed results across current studies. For this reason, an in-depth analysis of the interactions between SARS-CoV2 and the ACE2 cardio-protective mechanism is warranted. Similarly, ACE2 receptors are also expressed in the cerebral cortex tissue, both in neurons and glia. Therefore, it seems very possible for both cardiovascular and cerebrovascular systems to be damaged leading to further dysregulation and increased risk of mortality risk. This review aims to discuss the current literature related to potential complications of COVID-19 infection with hypertension and the vasculature, including the cervical one. Finally, age is a significant prognostic indicator among COVID-19 patients. For a mean age group of 70 years, the main presenting symptoms include fever, shortness of breath, and a persistent cough. Elderly patients with cardiovascular comorbidities, particularly hypertension and diabetes, represent a significant group of critical cases with increased case fatality rates. With the current understanding of COVID-19, it is essential to explore the mechanisms by which SARS-CoV-2 operates to improve clinical outcomes for patients suffering from underlying cardiovascular diseases and reduce the risk of such conditions de novo.
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Affiliation(s)
- Yashvardhan Batta
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Cody King
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - John Johnson
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Natasha Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | | | - Georges Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
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21
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Suhan D, Padhy SK, Panda KG, Kelgaonkar A. Sub-internal limiting membrane haemorrhage as a manifestation of transiently deranged coagulation profile following SARS-CoV-2 infection. BMJ Case Rep 2022; 15:15/1/e247745. [PMID: 35027390 PMCID: PMC8762149 DOI: 10.1136/bcr-2021-247745] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Dinesh Suhan
- Vitreo-Retina, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneshwar, Odisha, India
| | - Srikanta Kumar Padhy
- Vitreo-Retina, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneshwar, Odisha, India
| | - Krushna Gopal Panda
- Vitreo-Retina, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneshwar, Odisha, India
| | - Anup Kelgaonkar
- Vitreo-Retina, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneshwar, Odisha, India
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22
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Melton A, Doyle-Meyers LA, Blair RV, Midkiff C, Melton HJ, Russell-Lodrigue K, Aye PP, Schiro F, Fahlberg M, Szeltner D, Spencer S, Beddingfield BJ, Goff K, Golden N, Penney T, Picou B, Hensley K, Chandler KE, Plante JA, Plante KS, Weaver SC, Roy CJ, Hoxie JA, Gao H, Montefiori DC, Mankowski JL, Bohm RP, Rappaport J, Maness NJ. The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease. PLoS Pathog 2021; 17:e1010162. [PMID: 34929014 PMCID: PMC8722729 DOI: 10.1371/journal.ppat.1010162] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 01/03/2022] [Accepted: 12/01/2021] [Indexed: 01/08/2023] Open
Abstract
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.
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Affiliation(s)
- Alexandra Melton
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Biomedical Science Training Program, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Lara A. Doyle-Meyers
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Robert V. Blair
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Cecily Midkiff
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Hunter J. Melton
- Florida State University, Department of Statistics, Tallahassee, Florida, United States of America
| | - Kasi Russell-Lodrigue
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Pyone P. Aye
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Faith Schiro
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Marissa Fahlberg
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Dawn Szeltner
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Skye Spencer
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | | | - Kelly Goff
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Nadia Golden
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Toni Penney
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Breanna Picou
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Krystle Hensley
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Kristin E. Chandler
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Jessica A. Plante
- World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America
| | - Kenneth S. Plante
- World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America
| | - Scott C. Weaver
- World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America
| | - Chad J. Roy
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - James A. Hoxie
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Hongmei Gao
- Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, United States of America
| | - David C. Montefiori
- Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, United States of America
| | - Joseph L. Mankowski
- Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
| | - Rudolf P. Bohm
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Jay Rappaport
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
| | - Nicholas J. Maness
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
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23
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Yadav R, Aroshidze B, Yadav V, Zahid U, Jayarangaiah A, Gandhi A, Gotlieb V. Observational Study of Thrombotic Events in a Random Cohort of Hospitalized COVID-19 Patients at a Community-Based Hospital of New York City During the Beginning of the 2020 Pandemic. Cureus 2021; 13:e18601. [PMID: 34765362 PMCID: PMC8572526 DOI: 10.7759/cureus.18601] [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] [Accepted: 10/08/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) continues to pose an unprecedented challenge for the entire world and the healthcare system. Different theories have been proposed elucidating the pathophysiological mechanisms attributing to high mortality and morbidity in COVID-19 infection. Out of them, thrombosis and procoagulant state have managed to earn the maximum limelight. We conducted an observational study based on data from randomly selected 349 hospitalized patients with COVID-19 infection in a community-based hospital in New York City during the first wave of the COVID-19 viral surge in March 2020. The main objective of our study was to assess the risk and occurrence of thrombotic events (both venous and arterial) among the hospitalized patients including the intensive care unit (ICU) and non-ICU admissions with confirmed COVID-19 infection. The primary outcome in our study was defined as the thrombotic events that included myocardial infarction (MI), deep venous thrombosis (DVT), cerebrovascular accidents (CVA), and pulmonary embolism (PE). The study correlated the association of thrombotic events with the level of biomarkers of interest: D-dimer >1000 ng/ml, troponin-I >1 ng/ml, or both. The association of D-dimers and troponin-I with thrombotic events was measured using both univariate and multivariate Cox proportional hazard (PH) regression analysis. Out of a total of 349 patients, 78 patients (22.35%) were found to have elevated biomarkers (D-dimer >1000 ng/ml and/or troponin-I >1 ng/ml) and were categorized as a high-risk group. Eighty-nine patients developed thrombotic complications (evidence of more than one thrombotic event was found in several patients). Two-hundred seventy-one (77.65%) patients had no documentation of thrombosis. The incidence of thrombotic events included myocardial infarction (MI; N=45; 12.8%), cerebrovascular accidents (CVA; N=16; 4.5%), deep venous thrombosis (DVT; N=16; 4.5%), and pulmonary embolism (PE; N=9; 2.57%).
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Affiliation(s)
- Ruchi Yadav
- Internal Medicine, Brookdale University Hospital and Medical Center, Brooklyn, USA
| | - Beka Aroshidze
- Internal Medicine, Brookdale University Hospital and Medical Center, Brooklyn, USA
| | - Vivek Yadav
- Pulmonary and Critical Care, State University of New York Downstate Health Sciences University, New York, USA
| | - Umar Zahid
- Nephrology, Brookdale University Hospital and Medical Center, Brooklyn, USA
| | - Apoorva Jayarangaiah
- Internal Medicine, New York City (NYC) Health and Hospitals/Jacobi Medical Center, Bronx, USA
| | - Anjula Gandhi
- Internal Medicine, Brookdale University Hospital and Medical Center, Brooklyn, USA
| | - Vladimir Gotlieb
- Hematology/Oncology, Brookdale University Hospital and Medical Center, Brooklyn, USA
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24
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Srivastava R, Kumar A. Use of aspirin in reduction of mortality of COVID-19 patients: A meta-analysis. Int J Clin Pract 2021; 75:e14515. [PMID: 34118111 PMCID: PMC8420464 DOI: 10.1111/ijcp.14515] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/06/2021] [Indexed: 12/15/2022] Open
Abstract
COVID-19 infection, affecting every one of us from the last year. Emerging reports have indicated thromboembolism in serious cases of COVID-19. The aspirin is useful to reduce mortality of serious patients with acute respiratory distress syndrome without COVID-19. Thus, we have conducted a metanalysis to find out the role of aspirin in the mortality of COVID-19 patients using RevMan 5. A total of 10 studies containing 56 696 COVID-19 patients were found appropriate for quantitative analysis. The quality of articles was assessed using Newcastle-Ottawa scale. The fixed-effect model was used to calculate the odds ratio with 95% confidence interval (CI). The odd ratio was found to be 0.70 [0.63, 0.77] which indicates a lesser likelihood of having death in COVID-19 patients in aspirin group as compared with non-aspirin group. However, no effect 0.00 [-0.04, 0.04] was observed after the exclusion of outliers. Thus, further clinical evidence is required to make valid conclusion.
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Affiliation(s)
- Ritika Srivastava
- Department of Pharmacology and Clinical ResearchDelhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
| | - Anoop Kumar
- Department of Pharmacology and Clinical ResearchDelhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India
- Department of PharmacologySchool of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research University (DPSRU), New Delhi, India
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25
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Sun B, Zhang B, Guo X, Liu WH, Pang GF, Yang LY, Jiang F, Zhang Q. Combined CT score, blood mononuclear cell count, LDH, and plasma D-dimer for viral pneumonia diagnosis: a retrospective study. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2021; 14:1022-1030. [PMID: 34760038 PMCID: PMC8569312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/18/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE Due to a continued increase in viral pneumonia incidence and resulting high mortality, fast and accurate diagnosis is important for effective management. This investigation examined the significance of blood biomarkers and the CT score in the early diagnosis of viral pneumonia. METHODS Patients who were hospitalized due to radiologically-confirmed pneumonia and underwent virus antigen rapid test were enrolled. Their clinical information was compared. Blood mononuclear cell count, LDH, and plasma D-dimer were obtained. To evaluate the utility of biomarker levels in differentiating viral pneumonia from other pneumonia, ROC curves were developed to analyze the AUC. The optimal cut-off thresholds, specificity, sensitivity, and predictive values were assessed using the Youden index. The added value of the multi-marker approach was delineated using IDI and Reclassification analyses using NRI; IDI and NRI values were examined with 95% CI. RESULTS Overall, 1163 inpatients were recruited between January 2017 and January 2021. They were sub-divided into the viral pneumonia (n = 563) and non-viral pneumonia (n = 600) categories. We found that the CT score, blood mononuclear cell count, LDH, and plasma D-dimer were markedly elevated in viral pneumonia patients. At an LDH threshold of 693.595 U/L, an AUC of ROC was 0.805 in differentiating viral pneumonia. The combination of CT score and blood biomarkers had an ROC AUC value of 0.908. CONCLUSIONS Combining elevated biomarkers with CT assessments outperformed the CT score alone in identifying viral pneumonia. It is crucial to better characterize the significance of biomarkers in combination with CT assessments in the diagnosis of viral pneumonia.
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Affiliation(s)
- Bo Sun
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Bo Zhang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General HospitalTianjin 300052, P. R. China
| | - Xiang Guo
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Wei-Hua Liu
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Gui-Fen Pang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Lin-Ying Yang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Feng Jiang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
| | - Qing Zhang
- Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical UniversityChengde 067000, P. R. China
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26
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Meena RA, Sharifpour M, Gaddh M, Cui X, Xie Y, Di M, Brewster LP, Duwayri Y, Alabi O. COVID-19-associated venous thromboembolism portends worse survival. Semin Vasc Surg 2021; 34:117-124. [PMID: 34642031 PMCID: PMC8351078 DOI: 10.1053/j.semvascsurg.2021.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/01/2021] [Accepted: 08/02/2021] [Indexed: 12/30/2022]
Abstract
Patients with coronavirus disease 2019 (COVID-19) seem to be at high risk for venous thromboembolism (VTE) development, but there is a paucity of data exploring both the natural history of COVID-19-associated VTE and the risk for poor outcomes after VTE development. This investigation aims to explore the relationship between COVID-19-associated VTE development and mortality. A prospectively maintained registry of patients older than 18 years admitted for COVID-19-related illnesses within an academic health care network between March and September 2020 was reviewed. Codes from the tenth revision of the International Classification of Diseases for VTE were collected. The charts of those patients with a code for VTE were manually reviewed to confirm VTE diagnosis. There were 2,552 patients admitted with COVID-19-related illnesses. One hundred and twenty-six patients (4.9%) developed a VTE. A disproportionate percentage of patients of Black race developed a VTE (70.9% VTE v 57.8% non-VTE; P = .012). A higher proportion of patients with VTE expired during their index hospitalization (22.8% VTE v 8.4% non-VTE; P < .001). On multivariable logistic regression analysis, VTE was independently associated with mortality (odds ratio = 3.17; 95% confidence interval, 1.9-5.2; P < .001). Hispanic/Latinx ethnicity was associated with decreased mortality (odds ratio = 0.45; 95% confidence interval, 0.21-1.00; P = .049). Hospitalized patients of Black race with COVID-19 were more prone to VTE development, and patients with COVID-19 who developed in-hospital VTE had roughly nearly threefold higher odds of mortality. Further emphasis should be placed on optimizing COVID-19 anticoagulation protocols to reduce mortality in this high-risk cohort.
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Affiliation(s)
- Richard A Meena
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322; Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road, Decatur, GA 30033.
| | | | - Manila Gaddh
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322
| | - Xiangqin Cui
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322; Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road, Decatur, GA 30033
| | - Yue Xie
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322
| | - Mengyu Di
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322
| | - Luke P Brewster
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322; Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road, Decatur, GA 30033
| | - Yazan Duwayri
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322
| | - Olamide Alabi
- Emory University, 1364 E Clifton Road NE, Atlanta, GA 30322; Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road, Decatur, GA 30033
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Humility: a virtue critical to both successful COVID-19 research and patient care. Dela J Public Health 2021; 6:20-21. [PMID: 34467123 PMCID: PMC8389104 DOI: 10.32481/djph.2020.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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28
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Sen S, Kannan NB, Kumar J, Rajan RP, Kumar K, Baliga G, Reddy H, Upadhyay A, Ramasamy K. Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review. Int Ophthalmol 2021; 42:323-336. [PMID: 34379290 PMCID: PMC8356207 DOI: 10.1007/s10792-021-01996-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 07/30/2021] [Indexed: 02/08/2023]
Abstract
Introduction The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic. Methods All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement. Results We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after. Conclusion Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.
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Affiliation(s)
- Sagnik Sen
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India.
| | | | - Jayant Kumar
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
| | - Renu P Rajan
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
| | - Karthik Kumar
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
| | - Girish Baliga
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
| | | | - Anubhav Upadhyay
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
| | - Kim Ramasamy
- Department of Retina and Vitreous, Aravind Eye Hospital, Madurai, India
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29
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Boraschi P, Giugliano L, Mercogliano G, Donati F, Romano S, Neri E. Abdominal and gastrointestinal manifestations in COVID-19 patients: Is imaging useful? World J Gastroenterol 2021; 27:4143-4159. [PMID: 34326615 PMCID: PMC8311532 DOI: 10.3748/wjg.v27.i26.4143] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/08/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) can be considered a systemic disease with a specific tropism for the vascular system, in which the alterations of the microcirculation have an important pathogenetic role. The lungs are the main organ involved in COVID-19, and severe progressive respiratory failure is the leading cause of death in the affected patients; however, many other organs can be involved with variable clinical manifestations. Concerning abdominal manifestations, the gastrointestinal tract and the hepatobiliary system are mainly affected, although the pancreas, urinary tract and spleen may also be involved. The most common gastrointestinal symptoms are loss of appetite, followed by nausea and vomiting, diarrhea and abdominal pain. Gastrointestinal imaging findings include bowel wall thickening, sometimes associated with hyperemia and mesenteric thickening, fluid-filled segments of the large bowel and rarely intestinal pneumatosis and ischemia. Hepatic involvement manifests as an increase in the enzymatic levels of alanine aminotransferase, aspartate aminotransferase, serum bilirubin and γ-glutamyl transferase with clinical manifestations in most cases mild and transient. The most frequent radiological features are hepatic steatosis, biliary sludge and gallstones. Edematous acute pancreatitis, kidney infarct and acute kidney injury from acute tubular necrosis have been described more rarely in COVID-19. Lastly, splenic involvement is characterized by splenomegaly and by the development of solitary or multifocal splenic infarcts with classic wedge-shaped or even rounded morphology, with irregular or smooth profiles. In summary, the abdominal radiological findings of COVID-19 are nonspecific and with poor pathological correlation reported in the literature. Ultrasound and particularly computed tomography with multiphasic acquisition are the diagnostic methods mainly utilized in COVID-19 patients with abdominal clinical symptoms and signs. Although radiological signs are not specific of abdominal and gastrointestinal involvement, the diagnostic imaging modalities and in particular computed tomography are helpful for the clinician in the management, evaluation of the severity and evolution of the COVID-19 patients.
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Affiliation(s)
- Piero Boraschi
- Department of Diagnostic Imaging, Second Division of Radiology, Azienda Ospedaliero-Universitaria Pisana-University of Pisa, Pisa 56124, Italy
| | - Luigi Giugliano
- Department of Radiology, University of Naples “Federico II”, Naples 80131, Italy
| | - Giuseppe Mercogliano
- Department of Radiology, University of Naples “Federico II”, Naples 80131, Italy
| | - Francescamaria Donati
- Department of Diagnostic Imaging, Second Division of Radiology, Azienda Ospedaliero-Universitaria Pisana-University of Pisa, Pisa 56124, Italy
| | - Stefania Romano
- Department of Diagnostic Imaging, Santa Maria delle Grazie Hospital, Naples 80078, Italy
| | - Emanuele Neri
- Diagnostic and Interventional Radiology, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa 56126, Italy
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Martha JW, Pranata R, Lim MA, Wibowo A, Akbar MR. Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: A systematic review and meta-analysis of adjusted effect estimates. Int J Infect Dis 2021; 108:6-12. [PMID: 34000418 PMCID: PMC8123385 DOI: 10.1016/j.ijid.2021.05.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND This study aimed to investigate whether the active prescription of low-dose aspirin during or prior to hospitalization affects mortality in patients with coronavirus disease 2019 (COVID-19). Aspirin is often prescribed for secondary prevention in patients with cardiovascular disease and other comorbidities that might increase mortality, and may therefore falsely demonstrate increased mortality. To reduce bias, only studies that performed an adjusted analysis were included in this review. METHODS A systematic literature search of PubMed, Scopus, Embase and Clinicaltrials.gov was performed, from inception until 16 April 2021. The exposure was active prescription of low-dose aspirin during or prior to hospitalization. The primary outcome was mortality. The pooled adjusted effect estimate was reported as relative risk (RR). RESULTS Six eligible studies were included in this meta-analysis, comprising 13,993 patients. The studies had low-to-moderate risk of bias based on the Newcastle-Ottawa Scale. The meta-analysis indicated that the use of low-dose aspirin was independently associated with reduced mortality {RR 0.46 [95% confidence interval (CI) 0.35-0.61], P < 0.001; I2 = 36.2%}. Subgroup analysis on in-hospital low-dose aspirin administration also showed a significant reduction in mortality [RR 0.39 (95% CI 0.16-0.96), P < 0.001; I2 = 47.0%]. CONCLUSION Use of low-dose aspirin is independently associated with reduced mortality in patients with COVID-19, with low certainty of evidence.
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Affiliation(s)
- Januar Wibawa Martha
- Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Padjadjaran, Rumah Sakit Umum Pusat Hasan Sadikin, Bandung, Indonesia.
| | - Raymond Pranata
- Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Padjadjaran, Rumah Sakit Umum Pusat Hasan Sadikin, Bandung, Indonesia; Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Indonesia.
| | | | - Arief Wibowo
- Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Padjadjaran, Rumah Sakit Umum Pusat Hasan Sadikin, Bandung, Indonesia.
| | - Mohammad Rizki Akbar
- Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Padjadjaran, Rumah Sakit Umum Pusat Hasan Sadikin, Bandung, Indonesia.
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Lisco G, De Tullio A, Stragapede A, Solimando AG, Albanese F, Capobianco M, Giagulli VA, Guastamacchia E, De Pergola G, Vacca A, Racanelli V, Triggiani V. COVID-19 and the Endocrine System: A Comprehensive Review on the Theme. J Clin Med 2021; 10:jcm10132920. [PMID: 34209964 PMCID: PMC8269331 DOI: 10.3390/jcm10132920] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/31/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Background and aim. The review aimed to summarize advances in the topic of endocrine diseases and coronavirus disease 2019 (COVID-19). Methods. Scientific and institutional websites and databases were searched and data were collected and organized, when plausible, to angle the discussion toward the following clinical issues. (1) Are patients with COVID-19 at higher risk of developing acute or late-onset endocrine diseases or dysfunction? (2) May the underlying endocrine diseases or dysfunctions be considered risk factors for poor prognosis once the infection has occurred? (3) Are there defined strategies to manage endocrine diseases despite pandemic-related constraints? Herein, the authors considered only relevant and more frequently observed endocrine diseases and disorders related to the hypothalamic-pituitary region, thyroid and parathyroid glands, calcium-phosphorus homeostasis and osteoporosis, adrenal glands, and gonads. Main. Data highlight the basis of some pathophysiological mechanisms and anatomical alterations of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-induced endocrine dysfunctions. Some conditions, such as adrenal insufficiency and cortisol excess, may be risk factors of worse clinical progression once the infection has occurred. These at-risk populations may require adequate education to avoid the SARS-CoV-2 infection and adequately manage medical therapy during the pandemic, even in emergencies. Endocrine disease management underwent a palpable restraint, especially procedures requiring obligate access to healthcare facilities for diagnostic and therapeutic purposes. Strategies of clinical triage to prioritize medical consultations, laboratory, instrumental evaluations, and digital telehealth solutions should be implemented to better deal with this probably long-term situation.
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Affiliation(s)
- Giuseppe Lisco
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.L.); (A.D.T.); (V.A.G.); (E.G.); (V.T.)
| | - Anna De Tullio
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.L.); (A.D.T.); (V.A.G.); (E.G.); (V.T.)
| | - Assunta Stragapede
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
| | - Antonio Giovanni Solimando
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
| | - Federica Albanese
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
| | - Martina Capobianco
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
| | - Vito Angelo Giagulli
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.L.); (A.D.T.); (V.A.G.); (E.G.); (V.T.)
| | - Edoardo Guastamacchia
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.L.); (A.D.T.); (V.A.G.); (E.G.); (V.T.)
| | - Giovanni De Pergola
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Aldo Moro, 70124 Bari, Italy;
- National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Castellana Grotte, Italy
| | - Angelo Vacca
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
| | - Vito Racanelli
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari School of Medicine, 70124 Bari, Italy; (A.S.); (A.G.S.); (F.A.); (M.C.); (A.V.)
- Correspondence: ; Tel.: +39-(0)-80-547-82-54
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (G.L.); (A.D.T.); (V.A.G.); (E.G.); (V.T.)
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Nader D, Fletcher N, Curley GF, Kerrigan SW. SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19. PLoS One 2021; 16:e0253347. [PMID: 34161337 PMCID: PMC8221465 DOI: 10.1371/journal.pone.0253347] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 06/02/2021] [Indexed: 12/14/2022] Open
Abstract
The unprecedented global COVID-19 pandemic has prompted a desperate international effort to accelerate the development of anti-viral candidates. For unknown reasons, COVID-19 infections are associated with adverse cardiovascular complications, implicating that vascular endothelial cells are essential in viral propagation. The etiological pathogen, SARS-CoV-2, has a higher reproductive number and infection rate than its predecessors, indicating it possesses novel characteristics that infers enhanced transmissibility. A unique K403R spike protein substitution encodes an Arg-Gly-Asp (RGD) motif, introducing a potential role for RGD-binding host integrins. Integrin αVβ3 is widely expressed across the host, particularly in the endothelium, which acts as the final barrier before microbial entry into the bloodstream. This mutagenesis creates an additional binding site, which may be sufficient to increase SARS-CoV-2 pathogenicity. Here, we investigate how SARS-CoV-2 passes from the epithelium to endothelium, the effects of αVβ3 antagonist, Cilengitide, on viral adhesion, vasculature permeability and leakage, and also report on a simulated interaction between the viral and host protein in-silico.
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Affiliation(s)
- Danielle Nader
- Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Nicola Fletcher
- School of Veterinary Medicine, Veterinary Science Centre, University College Dublin, Belfield, Dublin 4, Ireland
| | - Gerard F. Curley
- Department of Anaesthesia and Critical Care Medicine, RCSI University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
| | - Steven W. Kerrigan
- Cardiovascular Infection Research Group, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland
- * E-mail:
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Bagherani N, Smoller BR. Hypothesis: Designation of Liposomal Scavenger System for Fighting against 2019-nCoV. Infect Disord Drug Targets 2021; 22:e150621194093. [PMID: 34132188 DOI: 10.2174/1871526521666210615141036] [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: 12/04/2020] [Revised: 02/18/2021] [Accepted: 03/05/2021] [Indexed: 11/22/2022]
Abstract
2019 novel coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 virus, is a member of the family Coronaviridae, which is responsible for the current pandemic of disease COVID-19. It is the seventh member of the family Coronaviridae, which infects humans, after 229E, OC43, NL63, HKU1, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Fever, dry cough and severe pneumonia are seen as common symptoms at the early stages of COVID-19. Some cases progress to acute respiratory stress syndrome, septic shock, organ failure, and death. The development of an effective treatment or vaccination for treating or preventing this lethal condition is an urgent need in order to fight this crisis. Up to now, some effective vaccines with different efficacy profiles have been introduced. Herein, we have theoretically designed a scavenger system for gathering 2019-nCoVs, breaking them, and re-introducing them to the immune system.
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Affiliation(s)
- Nooshin Bagherani
- Department of Molecular Medicine, School of Advanced Medical Science, Tehran University of Medical School, Tehran, Iran
| | - Bruce R Smoller
- Department of Pathology, Professor, Department of Dermatology, University of Rochester, School of Medicine and Dentistry, United States
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Miranda Soriano RVD, Rossi Neto JM, Finger MA, Santos CCD, Lin-Wang HT. COVID-19 in heart transplant patients: Case reports from Brazil. Clin Transplant 2021; 35:e14330. [PMID: 34028903 PMCID: PMC8209934 DOI: 10.1111/ctr.14330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 04/14/2021] [Accepted: 04/15/2021] [Indexed: 01/08/2023]
Abstract
Introduction The COVID‐19 pandemic continues, with a late hyperinflammatory phase. The immunosuppressive therapy used in heart transplant patients, in theory, could reduce inflammation, thus benefitting patients with COVID‐19. So far, however, there is still very little literature on this subject. Methods This is a single‐center retrospective study. We described laboratory parameters and clinical outcomes from 11 heart transplant patients with COVID‐19 assisted at Dante Pazzanese Institute of Cardiology between March and July 2020. Results Patients with ages of between 35 and 79 years were enrolled, and heart transplantation ranged from 3 to 264 months. The main comorbidities were diabetes mellitus (9/11; 81.8%), hypertension (10/11; 90.9%), and chronic renal disease (6/11; 54.5%). Cyclosporine A was used in 10 (90.9%) patients, mycophenolate mofetil in 9 (81.8%) patients, and mTOR inhibitor in 5 (45.5%) patients. Fever and cough were observed in 8 (72.7%) patients, and dyspnea and gastrointestinal symptoms in 5 (45.5%) patients. Lymphopenia was observed in 10 (90.9%) patients and thrombocytopenia in 5 (45.5%) patients. The higher level of troponin associated with chest tomography above 50% of bilateral pulmonary infiltrates with ground‐glass opacity (GGO) was observed in those with the worst outcomes. Nine patients needed intensive care, and hospital stay ranged from 4 to 21 days, with 2 (18.2%) patients requiring vasopressor drugs and mechanical ventilation, and three (27.3%) patients dying due to COVID‐19 complications. Conclusion Heart transplant patients had similar symptoms and outcomes as the general population; immunosuppressive therapy seems not to have protected them. Patients who presented higher levels of troponin and D‐dimer, associated with greater GGO pulmonary infiltrates, had worse outcomes. More studies with larger cohorts may clarify immunosuppressive effects on COVID‐19 outcomes.
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Affiliation(s)
| | - Joao Manoel Rossi Neto
- Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil
| | - Marco Aurelio Finger
- Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil
| | | | - Hui Tzu Lin-Wang
- Laboratory of Molecular Investigation in Cardiology, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil
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Coronavirus Disease 2019: An Overview of the Complications and Management. Pharmacol Ther 2021. [DOI: 10.36922/itps.v4i1.1037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Since the first report of COVID-19 emerging in Wuhan, China, authorities in 216 countries and territories have reported about 47.3 million COVID-19 cases and 1.2 million deaths. The WHO guidelines for the management of COVID-19 are very limited to recommendations for managing symptoms and advice on careful management of pediatric patients, pregnant women, and patients with underlying comorbidities. There is no approved treatment for COVID-19 and guidelines vary between countries. In this review, first, a brief overview is provided on the basic knowledge about the virus, clinical features of the disease, and different diagnostic methods. Then, the relationship between COVID-19, various body systems, and other complications is discussed. Finallly, different management strategies are discussed, including those drawn on computational chemistry analyses, pre-clinical investigations, and clinical trials which involve pharmacological and non-pharmacological interventions. In conclusion, despite the recent approval of different vaccine candidates, more virological characteristics of SARS-CoV-2 are required to be explored, which may result in the discovery of more potential therapeutic targets leading to safer and more effective treatment to COVID-19.
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Galambos C, Bush D, Abman SH. Intrapulmonary bronchopulmonary anastomoses in COVID-19 respiratory failure. Eur Respir J 2021; 58:13993003.04397-2020. [PMID: 33863743 PMCID: PMC8051184 DOI: 10.1183/13993003.04397-2020] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 04/05/2021] [Indexed: 11/22/2022]
Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a devastating and worldwide pandemic disease known as coronavirus disease 2019 (COVID-19). COVID-19 causes acute hypoxic respiratory failure (COVID-ARF), a major cause of mortality and morbidity, with an incompletely understood pathophysiological mechanism. Gattinoniet al. [1] noted that COVID-19 patients with acute hypoxic respiratory failure have lung disease that is often characterised by a remarkable dissociation between relatively well-preserved lung mechanics, including lung compliance, and severe hypoxaemia. These findings are consistent with the concept that profound hypoxaemia occurring in ventilated patients with highly compliant lungs could be due to the loss of regulation of lung perfusion and impaired hypoxic pulmonary vasoconstriction. Early autopsy studies suggest that the lung circulation is a major target of coronavirus infection, which leads to striking pulmonary vascular disease due to variable degrees of thrombosis, apoptosis, oedema, inflammation and angiogenesis [2–4]. These changes contribute to dysregulation of the pulmonary vasculature, which induces perfusion abnormalities and contributes to the physiological phenotypes reported in COVID-19 pneumonia. Further, computed tomography suggests a unique “tree in bud” appearance of small pulmonary arteries [3] and transcranial agitated saline microbubble doppler studies of COVID-19 patients with hypoxaemia have demonstrated intrapulmonary shunting of these bubbles, and that the presence and degree of transpulmonary bubble transit correlates with the degree of hypoxaemia [5]. Despite these studies, histopathological correlates of severe hypoxaemia and shunt in the setting of relatively normal lung compliance in COVID-19 patients are largely lacking. Open intrapulmonary bronchopulmonary anastomoses (IBA) were identified in COVID-19 patients who died of respiratory failure. IBA may be the microanatomical basis of intrapulmonary right to left shunt leading to severe hypoxaemia in COVID-19.https://bit.ly/3e2GajO
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Affiliation(s)
- Csaba Galambos
- Pediatric Heart Lung Center, Aurora, CO, USA .,Children's Hospital Colorado, Aurora, CO, USA.,University of Colorado Anschutz School of Medicine, Aurora, CO, USA
| | - Douglas Bush
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven H Abman
- Pediatric Heart Lung Center, Aurora, CO, USA.,Children's Hospital Colorado, Aurora, CO, USA.,University of Colorado Anschutz School of Medicine, Aurora, CO, USA
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Grandone E, Tiscia G, Pesavento R, De Laurenzo A, Ceccato D, Sartori MT, Mirabella L, Cinnella G, Mastroianno M, Dalfino L, Colaizzo D, Vettor R, Intrieri M, Ostuni A, Margaglione M. Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation. J Thromb Thrombolysis 2021; 52:772-778. [PMID: 33844150 PMCID: PMC8040353 DOI: 10.1007/s11239-021-02429-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/13/2021] [Indexed: 01/08/2023]
Abstract
It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.
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Affiliation(s)
- Elvira Grandone
- Thrombosis and Haemostasis Unit, Fondazione I.R.C.C.S. "Casa Sollievo della Sofferenza", Viale Cappuccini, S. Giovanni Rotondo, 71013, Foggia, Italy.
- Ob/Gyn Department of The First I.M. Sechenov Moscow State Medical University, Moscow, Russia.
| | - Giovanni Tiscia
- Thrombosis and Haemostasis Unit, Fondazione I.R.C.C.S. "Casa Sollievo della Sofferenza", Viale Cappuccini, S. Giovanni Rotondo, 71013, Foggia, Italy
| | | | - Antonio De Laurenzo
- Thrombosis and Haemostasis Unit, Fondazione I.R.C.C.S. "Casa Sollievo della Sofferenza", Viale Cappuccini, S. Giovanni Rotondo, 71013, Foggia, Italy
| | - Davide Ceccato
- Department of Internal Medicine, University of Padua, Padua, Italy
| | | | - Lucia Mirabella
- Department of Anesthesia and Intensive Care, University of Foggia, Foggia, Italy
| | - Gilda Cinnella
- Department of Anesthesia and Intensive Care, University of Foggia, Foggia, Italy
| | - Mario Mastroianno
- Scientific Direction, Fondazione I.R.C.C.S. "Casa Sollievo Della Sofferenza", S. Giovanni Rotondo, Foggia, Italy
| | - Lidia Dalfino
- Anesthesia and Intensive Care Unit, University of Bari, Bari, Italy
| | - Donatella Colaizzo
- Thrombosis and Haemostasis Unit, Fondazione I.R.C.C.S. "Casa Sollievo della Sofferenza", Viale Cappuccini, S. Giovanni Rotondo, 71013, Foggia, Italy
| | - Roberto Vettor
- Department of Internal Medicine, University of Padua, Padua, Italy
| | - Mariano Intrieri
- Department of Medicine and Health Science "V. Tiberio", University of Molise, Campobasso, Italy
| | - Angelo Ostuni
- Immunohematology and Transfusion Medicine Service, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, University of Bari "Aldo Moro", and Struttura Regionale Coordinamento Puglia, Bari, Italy
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Willer BL, Mpody C, Tobias JD, Nafiu OO. Racial Disparities in Failure to Rescue Following Unplanned Reoperation in Pediatric Surgery. Anesth Analg 2021; 132:679-685. [PMID: 33332903 DOI: 10.1213/ane.0000000000005329] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Failure to rescue (FTR) and unplanned reoperation following an index surgical procedure are key indicators of the quality of surgical care. Given that differences in unplanned reoperation and FTR rates among racial groups may contribute to persistent disparities in postsurgical outcomes, we sought to determine whether racial differences exist in the risk of FTR among children who required unplanned reoperation following inpatient surgical procedures. METHODS We used the National Surgical Quality Improvement database (2012-2017) to assemble a cohort of children (<18 years), who underwent inpatient surgery and subsequently returned to the operating room within 30 days of the index surgery. We used logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of FTR, comparing African American (AA) to White children. We estimated the risk-adjusted odds ratio (aOR) for FTR by controlling the analyses for demographic characteristics, surgical profile, and preoperative comorbidities. We further evaluated the racial differences in FTR by stratifying the analyses by the timing of unplanned reoperation. RESULTS Of 276,917 children who underwent various inpatient surgical procedures, 10,425 (3.8%) required an unplanned reoperation, of whom 2016 (19.3%) were AA and 8409 (80.7%) were White. Being AA relative to being White was associated with a 2-fold increase in the odds of FTR (aOR: 2.03; 95% CI, 1.5-2.74; P < .001). Among children requiring early unplanned reoperation, AAs were 2.38 times more likely to die compared to their White peers (8.9% vs 3.4%; aOR: 2.38; 95% CI, 1.54-3.66; P < .001). In children with intermediate timing of return to the operating room, the risk of FTR was 80% greater for AA children compared to their White peers (2.2% vs 1.1%; aOR: 1.80; 95% CI, 1.07-3.02; P = .026). Typically, AA children die within 5 days (interquartile range [IQR]: 1-16) of reoperation while their White counterparts die within 9 days following reoperation (IQR: 2-26). CONCLUSIONS Among children requiring unplanned reoperation, AA patients were more likely to die than their White peers. This racial difference in FTR rate was most noticeable among children requiring early unplanned reoperation. Time to mortality following unplanned reoperation was shorter for AA than for White children. Race appears to be an important determinant of FTR following unplanned reoperation in children and it should be considered when designing interventions to optimize unplanned reoperation outcomes.
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Affiliation(s)
- Brittany L Willer
- From the Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio
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Padhy SK, Dcruz RP, Kelgaonkar A. Paracentral acute middle maculopathy following SARS-CoV-2 infection: the D-dimer hypothesis. BMJ Case Rep 2021; 14:14/3/e242043. [PMID: 33664047 PMCID: PMC7934752 DOI: 10.1136/bcr-2021-242043] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
- Srikanta Kumar Padhy
- Ophthalmology, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneswar, Orissa, India
| | - Rakhi P Dcruz
- Ophthalmology, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneswar, Orissa, India
| | - Anup Kelgaonkar
- Vitreo-Retina, LV Prasad Eye Institute Bhubaneswar Campus, Bhubaneshwar, Odisha, India
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Akbas EM, Akbas N. COVID-19, adrenal gland, glucocorticoids, and adrenal insufficiency. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021; 165:1-7. [PMID: 33542545 DOI: 10.5507/bp.2021.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 01/21/2021] [Indexed: 01/08/2023] Open
Abstract
The current Coronavirus disease outbreak requires that physicians work in collaboration with other physicians especially in intensive care and emergency units. To fight against this new disease, whose pathogenesis, effects, and results have not been clearly demonstrated, especially in patients with the pre-existing chronic disease, requires special expertise and perspectives. Due to the need for dynamic glucocorticoid treatment at different stages of the disease in patients with adrenal insufficiency, the existence of reports indicating that "coronavirus disease 2019" also affects the adrenal reserve, and the use of glucocorticoids also in advanced stages in patients with Coronavirus disease require this issue to be emphasized with precision. Herein, treatment of the pre-existing adrenal insufficiency in patients with actual Coronavirus disease and the effects of the this critical disease on the adrenal gland have been reviewed.
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Affiliation(s)
- Emin Murat Akbas
- Erzincan Binali Yildirim University, School of Medicine, Mengucek Gazi Training and Research Hospital, Department of Endocrinology, Erzincan, Turkey
| | - Nergis Akbas
- Mengucek Gazi Training and Research Hospital, Department of Obesity, Biochemistry, Erzincan, Turkey
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Saburi E, Abazari MF, Hassannia H, Mansour RN, Eshaghi-Gorji R, Gheibi M, Rahmati M, Enderami SE. The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19. Gene 2021; 777:145471. [PMID: 33549712 PMCID: PMC7860931 DOI: 10.1016/j.gene.2021.145471] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/24/2020] [Accepted: 01/28/2021] [Indexed: 12/20/2022]
Abstract
In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.
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Affiliation(s)
- Ehsan Saburi
- Medical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Hadi Hassannia
- Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Reza Eshaghi-Gorji
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mobina Gheibi
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Rahmati
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyed Ehsan Enderami
- Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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Terrigno VR, Ricketti DA, Patel P, Roy S. Recurrent chronic thromboembolic disease despite optimal anticoagulation in setting of recent COVID-19 infection. BMJ Case Rep 2021; 14:e238733. [PMID: 33509878 PMCID: PMC7844927 DOI: 10.1136/bcr-2020-238733] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2021] [Indexed: 01/30/2023] Open
Abstract
We present a case of a 38-year-old man with a history of chronic thromboembolic pulmonary hypertension on therapeutic anticoagulation and recent hospitalisation for COVID-19 disease who was hospitalised for recurrent acute pulmonary embolism despite therapeutic anticoagulation with warfarin (International Normalized Ratio (INR) of 3.0). Our case highlights the hypercoagulable state associated with COVID-19 disease and the absence of standardised approaches to anticoagulation treatment for this population.
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Affiliation(s)
| | | | - Pranav Patel
- Cardiology, Cooper University Health Care, Camden, New Jersey, USA
| | - Satyajeet Roy
- Internal Medicine, Cooper University Hospital, Cherry Hill, New Jersey, USA
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43
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Yeganegi M, Fattahi P. Management and Prevention of Cerebrovascular Accidents in SARS-CoV-2-Positive Patients Recovering from COVID-19: a Case Report and Review of Literature. SN COMPREHENSIVE CLINICAL MEDICINE 2021; 3:279-290. [PMID: 33490876 PMCID: PMC7811396 DOI: 10.1007/s42399-021-00744-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/05/2021] [Indexed: 12/16/2022]
Abstract
We discuss the current understanding of COVID-19's neurological implications, their basis, and the evolving clinical consensus with a focus on cerebrovascular stroke. We further illustrate the potential significance of these implications with the aid of an accompanying case report outlining the disease course and treatment of a COVID-19 patient suffering from ischemic stroke and pulmonary embolism. The ever-growing strain on the global healthcare system due to the spread of the novel coronavirus SARS-CoV-2 requires focused attention on urgent care of independent, coexisting, and associated comorbidities, including cerebrovascular accidents. For illustration purposes, we outline the case of a 68-year-old female presenting with COVID-19 subsequently complicated by bilateral pulmonary embolism and a right-sided cerebrovascular accident. The patient was successfully managed pharmacologically and discharged without significant neurological deficit. The evidence for a hypercoagulable state in this patient along with discussion of mechanistic bases, corroborative evidence from the literature, along with relevant guidance on screening, treatment, and prophylaxis is offered. Greater study of the pathogenesis of COVID-19-related cerebrovascular complications and revisiting current guidelines on their management including potentially heightened levels of thromboprophylaxis are warranted.
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Affiliation(s)
- Masoud Yeganegi
- University of Toronto, Toronto, Ontario Canada
- Jagiellonian University Medical College, Kraków, Poland
| | - Pooia Fattahi
- Department of Neurology and Internal Medicine, Yale University, New Haven, CT USA
- Trinity Health of New England Neurology, Waterbury, CT USA
- Waterbury Neurology, 1579 Straits Turnpike, Suite 2A, Middlebury, CT 06762 USA
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44
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Adams E, Broce M, Mousa A. Proposed Algorithm for Treatment of Pulmonary Embolism in COVID-19 Patients. Ann Vasc Surg 2021; 70:282-285. [PMID: 32891745 PMCID: PMC7471764 DOI: 10.1016/j.avsg.2020.08.088] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023]
Abstract
There is mounting evidence that COVID-19 patients may possess a hypercoagulable profile that increases their risk for thromboembolic complications, including pulmonary embolism (PE). PE has been associated with an increase in morbidity, mortality, prolonged ventilation, and extended ICU admissions. Intervention is warranted in some patients who develop acute massive and submassive PEs. However, the development of PE in COVID-19 patients is often complicated by such factors as delay of diagnosis, confounding medical conditions, and strict isolation precautions. In addition, depleted cardiopulmonary reserve and prone positioning can make management of PE in these patients especially challenging for the physician. In this article, we review current understanding of PE in COVID-19 patients, summarize consensus data regarding the treatment of PE, and propose an algorithm to guide the management of COVID-19 patients with PE.
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Affiliation(s)
- Elliot Adams
- Department of Surgery, Charleston Area Medical Center/West Virginia University, Charleston, WV
| | - Mike Broce
- Center for Health Services and Outcomes Research, Charleston Area Medical Center Health Education and Research Institute, Charleston, WV
| | - Albeir Mousa
- Department of Surgery, Vascular and Endovascular Surgery Division, Charleston Area Medical Center/West Virginia University, Charleston, WV.
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45
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Sadoughi F, Maleki Dana P, Hallajzadeh J, Asemi Z, Mansournia MA, Yousefi B. Coagulopathy: Another side effect of coronavirus infection. J Cardiovasc Thorac Res 2020; 13:15-22. [PMID: 33815697 PMCID: PMC8007900 DOI: 10.34172/jcvtr.2020.59] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 11/02/2020] [Indexed: 01/08/2023] Open
Abstract
Recently, coronavirus disease 2019 (COVID-19) has been considered as a major health problem around the globe. This severe acute respiratory syndrome has a bunch of features, such as high transmission rate, which are adding to its importance. Overcoming this disease relies on a complete understanding of the viral structure, receptors, at-risk cells or tissues, and pathogenesis. Currently, researches have shown that besides the lack of a proper anti-viral therapeutic method, complications provided by this virus are also standing in the way of decreasing its mortality rate. One of these complications is believed to be a hematologic manifestation. Commonly, three kinds of coagulopathies are detected in COVID-19 patients: disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and deep vein thrombosis (DVT). In this paper, we have reviewed the relation between these conditions and coronavirus-related diseases pathogenesis, severity, and mortality rate.
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Affiliation(s)
- Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahman Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Shinu P, Morsy MA, Deb PK, Nair AB, Goyal M, Shah J, Kotta S. SARS CoV-2 Organotropism Associated Pathogenic Relationship of Gut-Brain Axis and Illness. Front Mol Biosci 2020; 7:606779. [PMID: 33415126 PMCID: PMC7783391 DOI: 10.3389/fmolb.2020.606779] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 11/30/2020] [Indexed: 12/16/2022] Open
Abstract
COVID-19 has resulted in a pandemic after its first appearance in a pneumonia patient in China in early December 2019. As per WHO, this global outbreak of novel COVID-19 has resulted in 28,329,790 laboratory-confirmed cases and 911,877 deaths which have been reported from 210 countries as on 12th Sep 2020. The major symptoms at the beginning of COVID-19 are fever (98%), tussis (76%), sore throat (17%), rhinorrhea (2%), chest pain (2%), and myalgia or fatigue (44%). Furthermore, acute respiratory distress syndrome (61.1%), cardiac dysrhythmia (44.4%), shock (30.6%), hemoptysis (5%), stroke (5%), acute cardiac injury (12%), acute kidney injury (36.6%), dermatological symptoms with maculopapular exanthema (36.1%), and death can occur in severe cases. Even though human coronavirus (CoV) is mainly responsible for the infections of the respiratory tract, some studies have shown CoV (in case of Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) to possess potential to spread to extra-pulmonary organs including the nervous system as well as gastrointestinal tract (GIT). Patients infected with COVID-19 have also shown symptoms associated with neurological and enteric infection like disorders related to smell/taste, loss of appetite, nausea, emesis, diarrhea, and pain in the abdomen. In the present review, we attempt to evaluate the understanding of basic mechanisms involved in clinical manifestations of COVID-19, mainly focusing on interaction of COVID-19 with gut-brain axis. This review combines both biological characteristics of the virus and its clinical manifestations in order to comprehend an insight into the fundamental potential mechanisms of COVID-19 virus infection, and thus endorse in the advancement of prophylactic and treatment strategies.
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Affiliation(s)
- Pottathil Shinu
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mohamed A Morsy
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.,Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt
| | - Pran Kishore Deb
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman, Jordan
| | - Anroop B Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Manoj Goyal
- Department of Anesthesia Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Jigar Shah
- Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, India
| | - Sabna Kotta
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
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Nwajei F, Anand P, Abdalkader M, Andreu Arasa VC, Aparicio HJ, Behbahani S, Curiale G, Daneshmand A, Dasenbrock H, Mayo T, Mian A, Nguyen T, Ong C, Romero JR, Sakai O, Takahashi C, Cervantes-Arslanian AM. Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature. J Stroke Cerebrovasc Dis 2020; 29:105412. [PMID: 33254367 PMCID: PMC7571902 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105412] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/18/2020] [Accepted: 10/13/2020] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate. Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported. The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone. OBJECTIVE To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19. METHODS We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center. Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions. RESULTS We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms. Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms. All patients were treated with intravenous hydration and anticoagulation. None suffered hemorrhagic complications, and all were discharged home. We identified 12 other patients with CVST in the setting of COVID-19 via literature search. There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%). CONCLUSIONS During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications. The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.
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Affiliation(s)
- Felix Nwajei
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA
| | - Pria Anand
- Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Mohamad Abdalkader
- Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Vanesa C Andreu Arasa
- Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Hugo J Aparicio
- Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Siavash Behbahani
- Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Gioacchino Curiale
- Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Ali Daneshmand
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA; Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Hormuzdiyar Dasenbrock
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA
| | - Thomas Mayo
- Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Asim Mian
- Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Thanh Nguyen
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA; Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA; Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Charlene Ong
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA; Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - J Rafael Romero
- Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Osamu Sakai
- Department of Radiology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Courtney Takahashi
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA; Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Anna M Cervantes-Arslanian
- Department of Neurosurgery, Boston University Medical Center, Boston, Massachusetts, USA; Department of Neurology, Boston University Medical Center, Boston, Massachusetts, USA; Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
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Murdaca G, Pioggia G, Negrini S. Vitamin D and Covid-19: an update on evidence and potential therapeutic implications. Clin Mol Allergy 2020; 18:23. [PMID: 33292313 PMCID: PMC7675394 DOI: 10.1186/s12948-020-00139-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 11/11/2020] [Indexed: 02/08/2023] Open
Abstract
The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.
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Affiliation(s)
- Giuseppe Murdaca
- Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, n. 6, 16132, Genova, Italy.
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164, Messina, Italy
| | - Simone Negrini
- Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, n. 6, 16132, Genova, Italy
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Eljilany I, Elzouki AN. D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review. Vasc Health Risk Manag 2020; 16:455-462. [PMID: 33223833 PMCID: PMC7672709 DOI: 10.2147/vhrm.s280962] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) emerged from the West District of Southern China Seafood Wholesale Market in late December 2019 and has been declared a global pandemic by the World Health Organization (WHO). Infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) presents with upper respiratory symptoms like cough, fever, and lethargy. At the same time, in later stages, critical COVID-19 patients develop acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), and multiple organ failure from cytokine storm and coagulation hyperactivity. Primary manifestations of thrombotic events include deep vein thrombosis (DVT), disseminated intravascular coagulation (DIC) and pulmonary embolism (PE). Initial coagulopathy in COVID-19 patients presents with elevated fibrin degradation products, especially D-dimers. In contrast, late presentations show evidence of prolonged prothrombin time (PT) and activated partial thromboplastin (aPTT), increased platelets, and fibrinogen levels. Diagnosis and monitoring of disease progression are done by regular screening of laboratory parameters, including D-dimer and fibrinogen. Management of coagulopathy in COVID-19 patients is like that of critically ill patients, including thromboprophylaxis. Coagulopathy is a poor prognostic factor, and optimum strategies should be developed for early diagnosis, prevention, and prompt treatment of VTE in COVID-19 patients. Thrombosis prophylaxis with low molecular weight heparin (LMWH) has shown beneficial results in preventing coagulopathy a reducing risk of mortality due to thrombotic events. We will discuss VTE in COVID-19 patients highlighting the role of D-dimer, fibrinogen, and interleukin-6 (IL-6).
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Affiliation(s)
| | - Abdel-Naser Elzouki
- Hamad Medical Corporation, Hamad General Hospital, Department of Medicine, Doha, Qatar
- Department of Medicine, Qatar University, College of Medicine, Doha, Qatar
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50
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Marchandot B, Trimaille A, Curtiaud A, Matsushita K, Jesel L, Morel O. Thromboprophylaxis: balancing evidence and experience during the COVID-19 pandemic. J Thromb Thrombolysis 2020; 50:799-808. [PMID: 32696172 PMCID: PMC7372740 DOI: 10.1007/s11239-020-02231-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
A common and potent consideration has recently entered the landscape of the novel coronavirus disease of 2019 (COVID-19): venous thromboembolism (VTE). COVID-19 has been associated to a distinctive related coagulopathy that shows unique characteristics. The research community has risen to the challenges posed by this « evolving COVID-19 coagulopathy » and has made unprecedented efforts to promptly address its distinct characteristics. In such difficult time, both national and international societies of thrombosis and hemostasis released prompt and timely responses to guide recognition and management of COVID-19-related coagulopathy. However, latest guidelines released by the international Society on Thrombosis and Haemostasis (ISTH) on May 27, 2020, followed the American College of Chest Physicians (CHEST) on June 2, 2020 showed some discrepancies regarding thromboprophylaxis use. In this forum article, we would like to offer an updated focus on thromboprophylaxis with current incidence of VTE in ICU and non-ICU patients according to recent published studies; highlight the main differences regarding ISTH and CHEST guidelines; summarize and describe which are the key ongoing RCTs testing different anticoagulation strategies in patients with COVID-19; and finally set a proposal for COVID-19 coagulopathy specific risk factors and dedicated trials.
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Affiliation(s)
- Benjamin Marchandot
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France
| | - Antonin Trimaille
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France
| | - Anais Curtiaud
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France
| | - Kensuke Matsushita
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, 67000, Strasbourg, France
| | - Laurence Jesel
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, 67000, Strasbourg, France
| | - Olivier Morel
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, 67000, Strasbourg, France.
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, 67000, Strasbourg, France.
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