The COVID-19 disease has spread rapidly across the world within just six months, affecting 169 million people and causing 3.5 million deaths globally (2021). The most affected countries include the USA, Brazil, India, and several European countries such as the UK and Russia. Healthcare professionals face new challenges in finding better ways to manage patients and save lives. In this regard, more comprehensive research is needed, including genomic and proteomic studies, personalized medicines and the design of suitable treatments. However, finding novel molecular entities (NME) using a standard or de novo strategy to drug development is a time-consuming and costly process. Another alternate strategy is discovering new therapeutic uses for old/existing/available medications, known as drug repurposing. There are a variety of computational repurposing methodologies, and some of them have been used to counter the coronavirus disease pandemic of 2019 (COVID-19). This review article compiles recently published data on the origin, transmission, pathogenesis, diagnosis, and management of the coronavirus by drug repurposing and vaccine development approach. We have attempted to screen probable drugs in clinical trials by using literature survey. This systematic review aims to create priorities for future research of drugs repurposed and vaccine development for COVID-19.

Acute lung injury, COVID-19, lung cancer, and asthma are a few of the respiratory conditions that are the main causes of morbidity and mortality worldwide. The increasing incidence and mortality rates have attracted significant attention to the prevention and treatment of these conditions. In recent years, there has been a renewed interest in utilizing naturally derived compounds as therapeutic agents for respiratory diseases. Luteolin (Lut), a flavonoid compound, possesses an extensive range of pharmacological characteristics, encompassing anti-inflammatory, antioxidative, antineoplastic, and antimicrobial activities. However, a comprehensive summary of Lut's therapeutic effects and mechanisms in respiratory diseases remains lacking. This review examines the physicochemical properties, toxicity, and avenues of Lut's action in respiratory ailments. Lut exerts therapeutic effects through pathways such as nuclear factor kappa-B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and pyroptosis, modulating key processes such as the suppression of inflammatory mediators, attenuation of oxidative assault, and induction of apoptosis in lung cancer cells. This review strives to provide critical realizations into respiratory disease therapeutics and contribute to the foundation for drug development.

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and other small molecules across biological membranes. AQPs are involved in various physiological processes and pathological conditions, including cancer, making them as potential targets for anticancer therapy. However, the development of selective and effective inhibitors of AQPs remains a challenge. In this study, we explored the possibility of using natural sapogenins, a class of plant-derived aglycones of saponins with diverse biological activities, as potential inhibitors of AQPs. We performed molecular docking, dynamics simulation and binding energy calculation to investigate the binding and inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are overexpressed in various cancers. Our results showed that out of 19 sapogenins, 8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. These sapogenin also exhibited favourable binding affinities in the range of -7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. Furthermore, MD simulations provided insights into stability and dynamics of the sapogenin-AQP complexes. Most of the fluctuations in binding pocket were observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining protein-ligand complex showed stable root mean square deviation (RMSD) plots, strong hydrogen bonding interactions, stable solvent-accessible surface area (SASA) values and minimum distance to the receptor. These observations suggest that natural sapogenin hold promise as novel inhibitors of AQPs, offering a basis for the development of innovative therapeutic agents for cancer treatment. However, further validation of the identified compounds through experiments is essential for translating these findings into therapeutic applications.

SARS-CoV-2 and other viruses rely on the protease function of the TMPRSS2 protein to invade host cells. Despite cancer patients often experience poorer outcomes following SARS-CoV-2 infection, the role of TMPRSS2 in different cancer types has not yet been analyzed in detail. Therefore, the aim of the study was to determine the expression, function and clinical relevance of TMPRSS2 in tumors.

Publicly accessible RNA sequencing data from tumors, adjacent tissues and whole blood samples of COVID-19 patients as well as data from human tumor epithelial and endothelial cells infected with SARS-CoV-2 were analyzed for TMPRSS2 expression and correlated to the expression of immune-relevant genes and clinical parameters. In vitro models of cells transfected with TMPRSS2 (TMPRSS2high), siTMPRSS2 or mock controls (TMPRSS2low cells) were analyzed by qPCR, flow cytometry, ELISA and Western blot for the expression of immune response-relevant molecules. Co-cultures of TMPRSS2 model systems with blood peripheral mononuclear cells were employed to evaluate immune cell migration, cytotoxicity and cytokine release.

Higher expression levels of TMPRSS2 were found in blood from patients infected with SARS-CoV-2, while TMPRSS2 expression levels significantly varied between the tumor types analyzed. TMPRSS2high tumor cells exhibit increased activity of the interferon (IFN) signal pathway accompanied by an increased expression of class I human leukocyte antigens (HLA-I) and programmed cell death ligand 1 (PD-L1) elevated interleukin 6 (IL-6) secretion and reduced NK cell-mediated cytotoxicity compared to TMPRSS2low mock controls. Treatment with a Janus kinase (JAK) 2 inhibitor or TMPRSS2-specific siRNA decreased TMPRSS2 expression. Co-cultures of the in vitro TMPRSS2 models with peripheral blood mononuclear cells in the presence of the immune checkpoint inhibitor nivolumab resulted in a significantly increased migration and infiltration of immune cells towards TMPRSS2high cells and a reduced release of the innate immunity-related cytokines CCL2 and CCL3.

This study provides novel insights into the role of TMPRSS2 in various tumor systems and the impact of SARS-CoV-2 infection on the host immunogenicity via the activation of immune-relevant pathways. These findings were linked to the efficacy of immune checkpoint inhibitor therapy, offering a potential alternative strategy to mitigate the severity of COVID-19.

Maintenance of genomic integrity is a fundamental characteristic of viruses, however, RNA-dependent RNA Polymerase (RdRp) lacks exonuclease activity for proofreading. To facilitate genomic proofreading in viruses, an independent exonuclease domain assists RdRp to maintain fidelity during replication. In contrast to high fidelity in DNA viruses, RNA viruses have to evolve into new variants through comparatively delicate mutagenesis activity for genetic diversity. Coronavirideae, a family of single positive-stranded RNA (+ ssRNA) viruses, meticulously sustain a balance between genetic diversity and large-size RNA genome. In coronaviruses, the proofreading activity is accomplished by an exonuclease (ExoN) domain located at the N-terminal of non-structural protein 14 (nsp14). ExoN is responsible for the new variants and antiviral resistance towards nucleotide analogs. Here, we provide an evolutionary characterization of ExoN by using a well-defined phylogenetic pipeline and structural analysis based on host and habitat. We carried out a phylogenetic analysis on ExoN, methyltransferase domain, nsp14, and whole genomes of ExoN-containing viruses. Furthermore, a three-dimensional structural comparison of the ExoN domain from various sources is also carried out to understand structural preservation. Our study has unveiled the evolutionary trajectories and structural conservation of the ExoN domain within the Coronaviridae family, highlighting its distinct evolutionary path independent of other domains. Structural analyses revealed minimal variance in RMSD values, underscoring the conserved nature of ExoN despite diverse ecological settings.

Infectious bronchitis virus (IBV) does not only cause disease in millions of chickens worldwide, but IBV-like viruses have also been detected or isolated from other domestic birds. We propose that the pheasant coronavirus (PhCoV) originates from IBV. Indeed, the IBV strains H120 and M41 can replicate but do not cause disease in pheasants. In this study, we found that three chicken nephropathogenic IBV strains, including ck/CH/LDL/091,021, ck/CH/LDL/140,520, and I0305/19, and the viruses recovered from the tissues of pheasants challenged with each IBV strain could replicate in some challenged pheasants with different capacities but could not cause disease. Overall, these viruses showed different capacities of replication and adaptation in pheasants, and the neutralizing antibody against each IBV strain could be detected in different numbers of pheasants challenged with each of the viruses, although the titers were generally low with large variation. Comparatively, ck/CH/LDL/140,520 and 20/P1-D5/Tr1 showed higher adaptation capacities in pheasants. Furthermore, the three IBV strains gained an increased capacity for adaptation when they passed in pheasants once, especially strain ck/CH/LDL/140,520, which gained an increased capacity for adaptation and extended tissue tropism when it was passaged in pheasants. Similar to IBV in chicken, the subpopulations within the virus were selected when the virus replicated and was passaged in pheasants, and the accumulation of mutations and deletions in the genome of each virus subpopulation accounted for the independent evolution of the virus in different tissues of pheasants. Taken together, we suggest that the phCoVs might originate from IBV through interspecies transmission from chickens to pheasants, before gaining increased tissue tropism, adaptation capacities, and disease-causing behaviors in pheasants during intraspecies transmission.

The COVID-19 pandemic has revolutionized vaccine production and compelled a massive global vaccination campaign. This study aimed to estimate the positivity and levels of SARS-CoV-2 IgG antibodies acquired due to vaccination and infection in the academic population of a Portuguese university.

Blood samples were collected and analyzed through the ELISA methodology, and statistical analysis was performed.

A total of 529 volunteers with at least one dose of the vaccine were enrolled in this study. Individuals without a prior COVID-19 diagnosis were divided into two groups: 350, who received a full vaccination, and 114, who received a full vaccination and a booster dose of the same vaccine (81) and mixed vaccines (33). Regarding the individuals who reported a prior SARS-CoV-2 infection, 31 received a full vaccination, and 34 received only one vaccination dose. Data analysis showed a higher level of IgG against SARS-CoV-2 in individuals who were younger, female, who received the Moderna vaccine, with recent post-vaccine administration, a mixed booster dose, and prior SARS-CoV-2 infection.

Assessing vaccination's effectiveness and group immunity is crucial for pandemic management, particularly in academic environments with high individual mobility, in order to define groups at risk and redirect infection control strategies.

Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.

The emergence of new techniques in both microbial biotechnology and artificial intelligence (AI) is opening up a completely new field for monitoring and sometimes even controlling the evolution of pathogens. However, the now famous generative AI extracts and reorganizes prior knowledge from large datasets, making it poorly suited to making predictions in an unreliable future. In contrast, an unfamiliar perspective can help us identify key issues related to the emergence of new technologies, such as those arising from synthetic biology, whilst revisiting old views of AI or including generative AI as a generator of abduction as a resource. This could enable us to identify dangerous situations that are bound to emerge in the not-too-distant future, and prepare ourselves to anticipate when and where they will occur. Here, we emphasize the fact that amongst the many causes of pathogen outbreaks, often driven by the explosion of the human population, laboratory accidents are a major cause of epidemics. This review, limited to animal pathogens, concludes with a discussion of potential epidemic origins based on unusual organisms or associations of organisms that have rarely been highlighted or studied.

COVID-19, caused by the novel coronavirus SARS-CoV-2, has presented a significant challenge to global health, security, and the economy. Vaccination is considered a crucial measure in preventing virus transmission. The silkworm bioreactor has gained widespread usage in antigen presentation, monoclonal antibody preparation, and subunit vaccine development due to its safety, efficiency, convenience, and cost-effectiveness. In this study, we employed silkworm BmN cells and the silkworm MultiBac multigene co-expression system to successfully produce two prototype vaccines: a recombinant baculovirus vector vaccine (NPV) co-displaying the SARS-CoV-2 virus capsid protein and a capsid protein virus-like particle (VLP) vaccine. Following the purification of these vaccines, we immunized BALB/c mice to evaluate their immunogenicity. Our results demonstrated that both VLP and NPV prototype vaccines effectively elicited robust immune responses in mice. However, when equal inoculation doses between groups were compared, the recombinant NPV vaccine exhibited significantly higher serum antibody titers and increased expression of spleen cytokines and lymphocyte immune regulatory factors compared to the VLP group. These results suggested an increased immune efficacy of the recombinant NPV vaccine. Conversely, the VLP prototype vaccine displayed more pronounced effects on lymphocyte cell differentiation induction. This study successfully constructed two distinct morphological recombinant vaccine models and systematically elucidated their differences in humoral immune response and lymphocyte differentiation rate. Furthermore, it has fully harnessed the immense potential of silkworm bioreactors for vaccine research and development, providing valuable technical insights for studying mutated viruses like coronaviruses.

The emergence of SARS-CoV-2 has triggered a global pandemic with profound implications for public health. Rapid changes in the pandemic landscape and limitations in in vitro diagnostics led to the introduction of numerous diagnostic devices with variable performance. In this study, we evaluated three commercial serological assays in Brazil for detecting anti-SARS-CoV-2 antibodies.

We collected 90 serum samples from SARS-CoV-2-negative blood donors and 352 from SARS-CoV-2-positive, unvaccinated patients, categorized by symptom onset. Subsequently, we assessed the diagnostic performance of three commercial enzyme immunoassays: GOLD ELISA (enzyme-linked immunosorbent assay) COVID-19 Ig (immunoglobulin) G + IgM, Anti-SARS-CoV-2 NCP IgM ELISA, and Anti-SARS-CoV-2 NCP IgG ELISA.

Our findings revealed that the GOLD ELISA COVID-19 IgG + IgM exhibited the highest sensitivity (57.7%) and diagnostic odds ratio, surpassing the manufacturer's reported sensitivity in most analyzed time frames while maintaining exceptional specificity (98.9%). Conversely, the Anti-SARS-CoV-2 NCP IgG ELISA demonstrated lower sensitivity but aligned with independent evaluations, boasting a specificity of 100%. However, the Anti-SARS-CoV-2 NCP IgM ELISA exhibited lower sensitivity than claimed, particularly in samples collected shortly after positive reverse transcription polymerase chain reaction results. Performance improved 15-21 days after symptom onset and beyond 22 days, but in the first week, both Anti-SARS-CoV-2 NCP IgM ELISA and Anti-SARS-CoV-2 NCP IgG ELISA struggled to differentiate positive and negative samples.

Our study emphasizes the need for standardized validation protocols to address discrepancies between manufacturer-claimed and actual performance. These insights provide essential information for health care practitioners and policymakers regarding the diagnostic capabilities of these assays in various clinical scenarios.

The COVID-19 pandemic poses ongoing challenges to the sustainability of various socioeconomic sectors, including agriculture, the food supply chain, the food business, and environmental sustainability. This study employs data obtained from the World Health Organization (WHO), and Food and Agriculture Organization (FAO), as well as scientific and technical research publications, to evaluate the impacts of COVID-19 on agriculture and food security. This article seeks to highlight the profound influence of the COVID-19 pandemic on agriculture, the supply and demand of food, and the overall safety of food. The article also explores the several pathways by which COVID-19 can be transmitted in these areas and the various technologies employed for its detection. The ongoing and post-pandemic ramifications are substantial since they could decrease agricultural output due to limitations on migration, a downturn in international trade, less buying capacity, and disturbances in food production and processing. Therefore, based on this thorough investigation, recommendations are issued for mitigating and controlling the pandemic's effects.

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (Mpro) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting Mpro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.

Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19.

ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients.

We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002).

In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Respiratory illness is the most common childhood disease globally, especially in developing countries. Previous studies have detected viruses in approximately 70-80% of respiratory illnesses.

In a prospective cohort study of 234 young children (ages 3-11 years) and 30 adults (ages 22-51 years) in rural Western Uganda sampled monthly from May 2019 to August 2021, only 24.2% of nasopharyngeal swabs collected during symptomatic disease had viruses detectable by multiplex PCR diagnostics and metagenomic sequencing. In the remaining 75.8% of swabs from symptomatic participants, we measured detection rates of respiratory bacteria Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae by quantitative PCR.

100% of children tested positive for at least one bacterial species. Detection rates were 87.2%, 96.8%, and 77.6% in children and 10.0%, 36.7%, and 13.3% for adults for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively. In children, 20.8% and 70.4% were coinfected with two and three pathogens, respectively, and in adults 6.7% were coinfected with three pathogens but none were coinfected with two. Detection of any of the three pathogens was not associated with season or respiratory symptoms severity, although parsing detection status by symptoms was challenged by children experiencing symptoms in 80.3% of monthly samplings, whereas adults only reported symptoms 26.6% of the time. Pathobiont colonization in children in Western Uganda was significantly more frequent than in children living in high-income countries, including in a study of age-matched US children that utilized identical diagnostic methods. Detection rates were, however, comparable to rates in children living in other Sub-Saharan African countries.

Overall, our results demonstrate that nonviral colds contribute significantly to respiratory disease burden among children in rural Uganda and that high rates of respiratory pathobiont colonization may play a role. These conclusions have implications for respiratory health interventions in the area, such as increasing childhood immunization rates and decreasing air pollutant exposure.

Human coronaviruses (HCoVs) are seriously associated with respiratory diseases in humans and animals. The first human pathogenic SARS-CoV emerged in 2002-2003. The second was MERS-CoV, reported from Jeddah, the Kingdom of Saudi Arabia, in 2012, and the third one was SARS-CoV-2, identified from Wuhan City, China, in late December 2019. The HCoV-Spike (S) gene has the highest mutation/insertion/deletion rate and has been the most utilized target for vaccine/antiviral development. In this manuscript, we discuss the genetic diversity, phylogenetic relationships, and recombination patterns of selected HCoVs with emphasis on the S protein gene of MERS-CoV and SARS-CoV-2 to elucidate the possible emergence of new variants/strains of coronavirus in the near future. The findings showed that MERS-CoV and SARS-CoV-2 have significant sequence identity with the selected HCoVs. The phylogenetic tree analysis formed a separate cluster for each HCoV. The recombination pattern analysis showed that the HCoV-NL63-Japan was a probable recombinant. The HCoV-NL63-USA was identified as a major parent while the HCoV-NL63-Netherland was identified as a minor parent. The recombination breakpoints start in the viral genome at the 142 nucleotide position and end at the 1082 nucleotide position with a 99% CI and Bonferroni-corrected p-value of 0.05. The findings of this study provide insightful information about HCoV-S gene diversity, recombination, and evolutionary patterns. Based on these data, it can be concluded that the possible emergence of new strains/variants of HCoV is imminent.

The aim of this study was to determine the short-term consequences of coronavirus disease 2019 (COVID-19) infection on pulmonary diffusion in patients with severe (but not critical) and moderately severe COVID-19 pneumonia during three months after COVID-19 infection.

A prospective study included 81 patients with an RT-PCR-test confirmed diagnosis of COVID-19 infection treated in the COVID Department of Lung Diseases of University Clinical Hospital Mostar. Inclusion criteria were ≥18-year-old patients, COVID-19 infection confirmed using real-time RT-PCR, radiologically confirmed bilateral COVID-19 pneumonia, and diffusion capacity of the lungs for carbon monoxide (DLCO) one and three months after COVID-19 infection. The pulmonary function was tested using the MasterScreen Body Jaeger (Jaeger Corporation, Omaha, USA) and MasterScreen PFT Jaeger (Jaeger Corporation, Omaha, USA) according to American Thoracic Society guidelines one and three months after COVID-19 infection.

Forced vital capacity significantly increased three months after COVID-19 infection compared to the first-month control (p<0.0005). Also, a statistically significant increase in the FEV1 value (p<0.0005), FEV1%FVC ratio (p<0.005), DLCO/SB (p<0.0005), DLCO/VA value (p<0.0005), and total lung capacity (TLC) (p<0.0005) was observed in all patients.

Our study showed that recovery of DLCO/VA and spirometry parameters was complete after three months, while DLCO/SB was below normal values even after three months. Therefore, one month after the COVID-19 infection patients had partial recovery of lung function, while a significant recovery of lung function was observed three months after the COVID-19 infection.

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.

To evaluate the influence of dietary patterns on the incidence and evolution of COVID-19. We hypothesised that a plant-based diet or a vegetarian diet compared with an omnivorous diet might be associated with a lower incidence of COVID-19 infection and severity in those infected.

In this observational study, 702 participants provided information on sociodemographic characteristics, dietary information and COVID-19 outcomes between March and July of 2022. Individuals were divided into two groups based on their dietary habits, omnivorous (n=424) and plant-based (n=278). The plant-based group was further divided into vegetarian and flexitarian subgroups. The groups were compared with respect to the incidence of COVID-19 infection, severity and duration. We used multivariable logistic regression models to evaluate the influence of dietary patterns.

Plant-based and vegetarian groups had a higher intake of vegetables, legumes and nuts, and lower intake of dairy and meat. After adjusting for important confounders, such as body mass index, physical activity and pre-existing medical conditions, the plant-based diet and vegetarian group had 39% (OR=0.61, 95% CI 0.44 to 0.85; p=0.003) and 39% (OR 0.61, 95% CI 0.42 to 0.88; p=0.009) lower odds of the incidence of COVID-19 infection, respectively, compared with the omnivorous group. No association was observed between self-reported diets and COVID-19 severity or duration.

Plant-based and mainly vegetarian diets were associated with a lower incidence of COVID-19 infection. These dietary patterns may be considered protective against COVID-19 infection. (Study protocol registered in CAAE: 54351421.4.0000.0068.).

Interactions between host and pathogenic microorganisms are common in nature and have a significant impact on host health, often leading to several types of infections. These interactions have evolved as a result of the ongoing battle between the host's defense mechanisms and the pathogens' invasion strategies. In this chapter, we will explore the evolution of host-pathogen interactions, explore their molecular mechanisms, examine the different stages of interaction, and discuss the development of pharmacological treatments. Understanding these interactions is crucial for improving public health, as it enables us to develop effective strategies to prevent and control infectious diseases. By gaining insights into the intricate dynamics between pathogens and their hosts, we can work towards reducing the burden of such diseases on society.

Coronaviruses (CoVs) belong to the RNA viruses family. The viruses in this family are known to cause mild respiratory disease in humans. The origin of the novel SARS-COV2 virus that caused the coronavirus-19 disease (COVID-19) is the Wuhan city in China from where it disseminated to cause a global pandemic. Although lungs are the predominant target organ for Coronavirus Disease-19 (COVID-19), since its outbreak, the disease is known to affect heart, blood vessels, kidney, intestine, liver and brain. This review aimed to summarize the catastrophic impacts of Coronavirus disease-19 on heart and liver along with its mechanisms of pathogenesis.

The information used in this review was obtained from relevant articles published on PubMed, Google Scholar, Google, WHO website, CDC and other sources. Key searching statements and phrases related to COVID-19 were used to retrieve information. Original research articles, review papers, research letters and case reports were used as a source of information.

Besides causing severe lung injury, COVID-19 has also been reported to affect and cause dysfunction of many other organs. COVID-19 infection can affect people by downregulating membrane-bound active angiotensin-converting enzyme (ACE). People who have deficient ACE2 expression are more vulnerable to COVID-19 infection. The patients' pre-existing co-morbidities are major risk factors that predispose individuals to severe COVID-19.

The disease severity and its broad spectrum phenotype is a result of combined direct and indirect pathogenic factors. Therefore, protocols that harmonize many therapeutic preferences should be the best alternatives to de-escalate the disease and obviate deaths caused as a result of multiple organ damage and dysfunction induced by the disease.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes acute coronavirus disease-19 (COVID-19) that has emerged on a pandemic level. Coronaviruses are well-known to have a negative impact on the lungs and cardiovascular system. SARS-CoV-2 induces a cytokine storm that primarily targets the lungs, causing widespread clinical disorders, including COVID-19. Although, SARS-CoV-2 positive individuals often show no or mild upper respiratory tract symptoms, severe cases can progress to acute respiratory distress syndrome (ARDS). Novel CoV-2 infection in 2019 resulted in viral pneumonia as well as other complications and extrapulmonary manifestation. ARDS is also linked to a higher risk of death. Now, it is essential to develop our perception of the long term sequelae coronavirus infection for the identification of COVID-19 survivors who are at higher risk of developing the chronic lung fibrosis. This review study was planned to provide an overview of the effects of SARS-CoV-2 infection on various parts of the respiratory system such as airways, pulmonary vascular, lung parenchymal and respiratory neuromuscular system as well as the potential mechanism of the ARDS related respiratory complications including the lung fibrosis in patients with severe COVID-19.

The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDAapproved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.

To investigate work and living conditions as determinants of COVID-19 infection risks in foreign-born workers in non-healthcare occupations.

Data were collected according to a qualitative design, using semistructured interviews. Verbatim transcripts of these interviews were analysed according to systematic text condensation.

We recruited foreign-born workers (n=15) and union representatives (n=6) among taxi drivers, bus and tram drivers, pizza bakers, cleaners and property caretakers, all indicated as risk occupations during COVID-19 in Sweden.

Four overarching themes were found: 'virus exposure at work', 'aspects of low status and undervalued work', 'lack of access to information' and 'foreign-born persons' position'. Virus exposure was frequent due to many social interactions over a workday, out of which several were physically close, sometimes to the point of touching. The respondents fulfilled important societal functions, but their work was undervalued due to low job status, and they had little influence on improving safety at work. Lack of health literacy limited foreign-born workers to access information about COVID-19 infection risks and protection, since most information from health organisations and employers was only available in Swedish and not adapted to their living conditions or disseminated through unknown channels. Instead, many turned to personal contacts or social media, through which a lot of misinformation was spread. Foreign-born persons were also subjected to exploitation since a Swedish residency permit could depend on maintaining employment, making it almost impossible to make demands for improved safety at work.

Structural factors and a lack of adapted information manifested themselves as fewer possibilities for protection against COVID-19. In a globalised world, new widespread diseases are likely to occur, and more knowledge is needed to protect all workers equally. Our results are transferable to similar contexts and bring forth aspects that can be tried in quantitative studies or public health interventions.Cite Now.

The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the greatest worldwide public health threat of this century, which may predispose multi-organ failure (especially the lung) and death despite numerous mild and moderate symptoms. Recent studies have unraveled the molecular and clinical characteristics of the infectivity, pathogenicity, and immune evasion of SARS-CoV-2 and thus improved the development of many different therapeutic strategies to combat COVID-19, including treatment and prevention. Previous studies have indicated that nitric oxide (NO) is an antimicrobial and anti-inflammatory molecule with key roles in pulmonary vascular function in the context of viral infections and other pulmonary disease states. This review summarized the recent advances of the pathogenesis of SARS-CoV-2, and accordingly elaborated on the potential application of NO in the management of patients with COVID-19 through antiviral activities and anti-inflammatory properties, which mitigate the propagation of this disease. Although there are some limits of NO in the treatment of COVID-19, it might be a worthy candidate in the multiple stages of COVID-19 prevention or therapy.

The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants.Communicated by Ramaswamy H. Sarma.

The devastating Coronavirus Disease 2019 (COVID-19) pandemic indicates that early detection of candidates with pandemic potential is vital. However, comprehensive metagenomic sequencing of the total microbiome is not practical due to the astronomical and rapidly evolving numbers and species of micro-organisms. Analysis of previous pandemics suggests that an increase in human-animal interactions, changes in animal and arthropod distribution due to climate change and deforestation, continuous mutations and interspecies jumping of RNA viruses, and frequent travels are important factors driving pandemic emergence. Besides measures mitigating these factors, surveillance at human-animal interfaces targeting animals with unusual tolerance to viral infections, sick heathcare workers, and workers at high biosafety level laboratories is crucial. Surveillance of sick travellers is important when alerted by an early warning system of a suspected outbreak due to unknown agents. These samples should be screened by multiplex nucleic acid amplification and subsequent unbiased next-generation sequencing. Novel viruses should be isolated in routine cell cultures, complemented by organoid cultures, and then tested in animal models for interspecies transmission potential. Potential agents are candidates for designing rapid diagnostics, therapeutics, and vaccines. For early detection of outbreaks, there are advantages in using event-based surveillance and artificial intelligence (AI), but high background noise and censorship are possible drawbacks. These systems are likely useful if they channel reliable information from frontline healthcare or veterinary workers and large international gatherings. Furthermore, sufficient regulation of high biosafety level laboratories, and stockpiling of broad spectrum antiviral drugs, vaccines, and personal protective equipment are indicated for pandemic preparedness.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.

Chalcones and their derivatives have been widely studied due to their versatile pharmacological and biological activities, such as anti-inflammatory, antibacterial, antiviral, and antitumor effects. These compounds have shown suitable antiviral effects through the selective targeting of a variety of viral enzymes, including lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, protein tyrosine phosphatase, topoisomerase-II, protein kinases, integrase/protease, and lactate/isocitrate dehydrogenase, among others. Chalcones and their derivatives have displayed excellent potential for combating pathogenic bacteria and fungi (especially, multidrug-resistant bacteria). However, relevant mechanisms should be further explored, focusing on inhibitory effects against DNA gyrase B, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), and efflux pumps (e.g., NorA), among others. In addition, the antifungal and antiparasitic activities of these compounds (e.g., antitrypanosomal and antileishmanial properties) have prompted additional explorations. Nonetheless, systematic analysis of the relevant mechanisms, biosafety issues, and pharmacological properties, as well as clinical translation studies, are vital for practical applications. Herein, recent advancements pertaining to the antibacterial, antiviral, antiparasitic, and antifungal activities of chalcones and their derivatives are deliberated, focusing on the relevant mechanisms of action, crucial challenges, and future prospects. Furthermore, due to the great importance of greener and more sustainable synthesis of these valuable compounds, especially on an industrial scale, the progress made in this field has been briefly discussed. Hopefully, this review can serve as a catalyst for researchers to delve deeper into the exploration and designing of novel chalcone compounds with medicinal properties, especially against pathogenic viruses and multidrug-resistant bacteria as major causes of concern for human health.

Since the coronavirus disease 19 (COVID-19), which caused several respiratory diseases, was formally declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, it affected the lifestyle and health of athletes, both directly through cardiorespiratory and other health related effects, and indirectly as the pandemic has forced the suspension, postponement, or cancellation of most professional sporting events around the world. In this review, we explore the journey of athletes throughout the pandemic and during their return to their competitive routine. We also highlight potential pitfalls during the process and summarize the recommendations for the optimal return to sport participation. We further discuss the impact of the pandemic on the psychology of athletes, the variance between the team and individual athletes, and their ability to cope with the changes. Moreover, we specifically reviewed the pandemic impact on younger professional athletes in terms of mental and fitness health. Finally, we shaded light on the various impacts of mass gathering events and recommendations for managing upcoming events.

Healthcare-associated infections are a global health problem and are more prevalent in developing countries such as Ethiopia, but there is a paucity of research on the infection prevention practices of cleaning staff. Therefore, this study aimed to assess infection prevention and control practices and associated factors among cleaners working in healthcare facilities in Gondar City, Ethiopia.

A cross-sectional survey was conducted among healthcare cleaning staff from May to June 2022. A total of 428 cleaners took part in the survey. Data were collected using a semi-structured interviewer-administered questionnaire. The data were entered into EpiData version 4.6 and analyzed using Stata version 14 software. A multivariable binary logistic regression analysis was used to ascertain the significance of associations at <0.05 p-value and the adjusted odds ratio (AOR) with a 95% confidence interval (CI).

Among the 390 study participants included, 294 (75.1%) were female. Of the surveyed participants, 186 (47.7%) had good knowledge of infection prevention and control practices. This study revealed that out of the 390 healthcare cleaners, 204 (52.3%) had good infection prevention and control practices with 52.3% [95% CI (47.2, 56.4)]. Good knowledge of infection prevention and control [AOR: 1.56, 95% CI (1.03, 2.37)] and the availability of infection prevention and control guidelines in the workplace [AOR: 1.54, 95% CI (1.01, 2.33)] were significant factors associated with infection prevention and control practice.

The present study found that almost half of the healthcare cleaners had poor IPC practices. The finding underlines the importance of good IPC knowledge and the accessibility of IPC guidelines to improve IPC practices among healthcare cleaning staff. The findings of this study also highlight that behavioral change interventions and paying attention, particularly to nonclinical staff such as cleaners in health care settings, are critical to reducing infection in health care settings.

The latest global pandemic corona virus disease - 2019 (COVID-19) caused by the virus SARS-CoV-2 is still a matter of worrying concern both for the scientific communities and health care organizations. COVID-19 disease is proved to be a highly contagious disease transmitted through respiratory droplets and even close contact with affected individuals. COVID-19 disease is also understood to exhibit diverse symptoms of ranging severities i.e., from mild fatigue to death. Affected individuals' susceptibility to induce immunologic dysregulation phenomena termed 'cytokine storm' seems to be playing the damaging role of escalating the disease manifestation from mild to severe. Cytokine storm in patients with severe symptoms is understood to be characterized by enhanced serum levels of many cytokines including interleukin-1β, interleukin-6, IL-10, TNF, interferon-γ, MIP-1α, MIP-1β and VEGF. Since cytokine production in general is the most important antiviral defense response, understanding the COVID-19 associated cytokine storm in particular and differentiating it from the regular cytokine production response becomes crucial in developing an effective therapeutic strategy.This review focuses on the potential targeting of COVID-19 associated cytokine storm and its challenges.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence in 2019 led to global health crises and the persistent risk of viral mutations. To combat SARS-CoV-2 variants, researchers have explored new approaches to identifying potential targets for coronaviruses. This study aimed to identify SARS-CoV-2 inhibitors using drug repurposing. In silico studies and network pharmacology were conducted to validate targets and coronavirus-associated diseases to select potential candidates, and in vitro assays were performed to evaluate the antiviral effects of the candidate drugs to elucidate the mechanisms of the viruses at the molecular level and determine the effective antiviral drugs for them. Plaque and cytopathic effect reduction were evaluated, and real-time quantitative reverse transcription was used to evaluate the antiviral activity of the candidate drugs against SARS-CoV-2 variants in vitro. Finally, a comparison was made between the molecular docking binding affinities of fenofibrate and remdesivir (positive control) to conventional and identified targets validated from protein-protein interaction (PPI). Seven candidate drugs were obtained based on the biological targets of the coronavirus, and potential targets were identified by constructing complex disease targets and PPI networks. Among the candidates, fenofibrate exhibited the strongest inhibition effect 1 h after Vero E6 cell infection with SARS-CoV-2 variants. This study identified potential targets for coronavirus disease (COVID-19) and SARS-CoV-2 and suggested fenofibrate as a potential therapy for COVID-19.

The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong.

With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed.

Between period 1 and 2, we observed a significant increase in the trend of CRA infections (P<0.001), while there was no significant increase in the trend of MRSA (P=0.742) and ESBL-producing Enterobacterales (P=0.061) infections. Meanwhile, a significant increase in the trend of carbapenems (P<0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) (P=0.045), and fluoroquinolones (P=0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p=0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P=0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients.

Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption.

All coronaviruses are characterized by spike glycoproteins whose S1 subunits contain the receptor binding domain (RBD). The RBD anchors the virus to the host cellular membrane to regulate the virus transmissibility and infectious process. Although the protein/receptor interaction mainly depends on the spike's conformation, particularly on its S1 unit, their secondary structures are poorly known. In this paper, the S1 conformation was investigated for MERS-CoV, SARS-CoV, and SARS-CoV-2 at serological pH by measuring their Amide I infrared absorption bands. The SARS-CoV-2 S1 secondary structure revealed a strong difference compared to those of MERS-CoV and SARS-CoV, with a significant presence of extended β-sheets. Furthermore, the conformation of the SARS-CoV-2 S1 showed a significant change by moving from serological pH to mild acidic and alkaline pH conditions. Both results suggest the capability of infrared spectroscopy to follow the secondary structure adaptation of the SARS-CoV-2 S1 to different environments.