Causes Coronavirus Disease 2019 Research Articles

SARS-CoV-2 (COVID-19) as a possible risk factor for neurodevelopmental disorders.

Pregnant women constitute one of the most vulnerable populations to be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019. SARS-CoV-2 infection during pregnancy could negatively impact fetal brain development via multiple mechanisms. Accumulating evidence indicates that mother to fetus transmission of SARS-CoV-2 does occur, albeit rarely. When it does occur, there is a potential for neuroinvasion via immune cells, retrograde axonal transport, and olfactory bulb and lymphatic pathways. In the absence of maternal to fetal transmission, there is still the potential for negative neurodevelopmental outcomes as a consequence of disrupted placental development and function leading to preeclampsia, preterm birth, and intrauterine growth restriction. In addition, maternal immune activation may lead to hypomyelination, microglial activation, white matter damage, and reduced neurogenesis in the developing fetus. Moreover, maternal immune activation can disrupt the maternal or fetal hypothalamic-pituitary-adrenal (HPA) axis leading to altered neurodevelopment. Finally, pro-inflammatory cytokines can potentially alter epigenetic processes within the developing brain. In this review, we address each of these potential mechanisms. We propose that SARS-CoV-2 could lead to neurodevelopmental disorders in a subset of pregnant women and that long-term studies are warranted.

Combining computational and experimental evidence on the activity of antimalarial drugs on papain-like protease of SARS-CoV-2: A repurposing study.

The development of inhibitors that target the papain-like protease (PLpro) has the potential to counteract the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent causing coronavirus disease 2019 (COVID-19). Based on a consideration of its several downstream effects, interfering with PLpro would both revert immune suppression exerted by the virus and inhibit viral replication. By following a repurposing strategy, the current study evaluates the potential of antimalarial drugs as PLpro inhibitors, and thereby the possibility of their use for treatment of SARS-CoV-2 infection. Computational tools were employed for structural analysis, molecular docking, and molecular dynamics simulations to screen antimalarial drugs against PLpro, and in silico data were validated by in vitro experiments. Virtual screening highlighted amodiaquine and methylene blue as the best candidates, and these findings were complemented by the in vitro results that indicated amodiaquine as a μM PLpro deubiquitinase inhibitor. The results of this study demonstrate that the computational workflow adopted here can correctly identify active compounds. Thus, the highlighted antimalarial drugs represent a starting point for the development of new PLpro inhibitors through structural optimization.

Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in "SAlpha", "SBeta", "SDelta", and "SOmicron", respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

Correlation Between Plasma Vitamin C Concentration and COVID-19 Outcomes among Patients Seen at a Major Hospital in the United Arab Emirates.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a newly emerged coronavirus that causes coronavirus disease-2019 (COVID-19) with varying degrees of disease manifestations. Vitamin C is an essential water-soluble vitamin with anti-inflammatory, antioxidant, antiviral, and immunomodulatory functions. The study aimed to investigate the association between serum vitamin C concentration and outcomes of COVID-19 among adults in the United Arab Emirates (UAE). This retrospective observational study included 67 COVID-19 patients aged 30-59 years old. Measurement of vitamin C levels was performed at the National Reference Laboratory, UAE using liquid chromatography-tandem mass spectrometry (LC/MS-MS). The cut-off value was 0.4 mg/dl; plasma levels that ranged from 0.4 to 2 mg/dl were defined as sufficient. Values above 2 mg/dl were recognized as high and values less than 0.4 mg/dl are considered low or deficient. Among the included patients, 58.2% suffered from vitamin C deficiency. We found a statistically significant correlation between the concentration of serum vitamin C and age (p=0.03), the presence of hypertension (p=0.013), diabetes (p=0.01), and the development of pneumonia (p=0.012). There was no significant correlation between the concentration of serum vitamin C and the need for mechanical ventilation, Intensive Care Unit (ICU) admission, COVID-19 severity, or mortality. The risk of COVID-19 severity decreased in patients with sufficient vitamin C levels by 52% compared to patients with vitamin C deficiency (p=0.177). There was a statistically significant correlation between vitamin C sufficiency and low lactate dehydrogenase, C-reactive protein (CRP), and fibrinogen. However, the odds of vitamin C sufficiency in COVID-19 patients were significantly associated with lowering CRP levels (OR=0.99, 95% CI (0.98-1.00), p=0.024). Low serum vitamin C concentrations were associated with several demographic characteristics of patients, the presence of pneumonia, and inflammation. Furthermore, improving our social determinants, such as how we live, eat, drink, and vitamin C supplementation could positively impact the future health of the individual, community, and population.

Awareness about Medicinal Indigenous Plants during COVID-19

The coronavirus family's severe acute respiratory syndrome coronavirus (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19). The disease became a pandemic after the fi rst case was identifi ed in Wuhan, China, December 2019. The present study is on “Awareness about medicinal indigenous plants during COVID-19” which was undertaken during 2021-2022 to see the Utility of medicinal indigenous plants to maintain immunity against COVID-19'' in four diff erent localities would be randomly selected in Kanpur district. 30 respondents will be selected randomly from each locality. Thus, in all 120 respondents will be selected for the study. Most of the respondents were belong to 30-40 years of age group, and majority of respondents in the study area were found to be post graduate and above, limited access to source of information television, mobile phones as their communication. The study concludes that most respondents were agree with awareness about medicinal indigenous plants during COVID-19. They were agreeing about Neem is anti-viral eff ect and Tulsi boosts the production of antibodies. The study also concluded that the respondents were agree about cloves helps to stop the growth of microorganism. Also, there was awareness regarding Ginger helps to prevent stress and promote healthy aging.

Immunosenescence and severity of COVID-19

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19). It is associated with significant morbidity and mortality, and socio-economic disruption globally. Increasing age and ageing-associated comorbidities such as obesity, type 2 diabetes, and chronic cardiac, respiratory, kidney and liver diseases are associated with greater risk of adverse outcomes including severe illness, hospitalisation, intensive care admission and death. Older individuals are disproportionately affected regardless of pre-existing comorbidities. Ageing-related changes to the immune system results in a less effective response to novel pathogens. Atrophy of the thymus and a consequentially reduced T cell receptor (TCR) repertoire maybe responsible for the increasing severity of infection with advancing age, as T cells play a crucial role in viral clearance generally and in COVID-19. Vaccination programmes are currently gaining momentum and could potentially provide a route out of the pandemic. Relevance: Viral pandemics are not uncommon; H1N1, Ebola, Zika, SARS, Middle East respiratory syndrome (MERS) and now COVID-19 have been a significant cause of public disturbance, morbidity, and mortality over the past two decades. We are likely to continue to encounter novel viral pathogens increasingly commonly in the coming years. Medical students should therefore develop an understanding of the immune response to viruses and take this opportunity to familiarise themselves with the features of the COVID-19 pandemic. An appreciation of immunosenescence is also key as our communities continue to age. Take home messages: • Symptoms of COVID-19 are heterogenous; individuals can be asymptomatic, have mild flu-like symptoms or severe respiratory disease and systemic complications. • A potent T cell and B cell response is present with SARS-COV-2 infection, with antibodies targeting the viral spike protein. • Immunosenescence is associated with a poorer response to novel and evolving pathogens. • Vaccines show high efficacy against COVID-19 and mass vaccination programmes could be the route out of the pandemic.

PP26 Cost Utility Of Vaccination Against COVID-19 In Brazil

IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a single-strand ribonucleic acid virus that was first identified in January 2020 in patients with viral pneumonia in Wuhan, China. The virus has since spread rapidly around the world, leading the World Health Organization to declare it a pandemic on 11 March 2020. In Brazil there have been 21.8 million cases of SARS-CoV-2 infection and 608,500 deaths. The objective of this study was to evaluate the cost utility of the Oxford, CoronaVac, and Janssen vaccines from the perspective of the Brazilian public health system.MethodsThree microsimulation models were constructed using individual data. The simulations contained seven transition states related to the natural history of COVID-19. The model with a daily cycle had a time horizon of one year and used data from 289 days of the pandemic. The analysis considered direct medical costs from the Brazilian health system perspective. Outpatient, hospital, and mortality databases were used for the model inputs and patient data were stratified by age. Effective vaccines reduced the likelihood of patients becoming ill. Information on the quality of life of patients receiving treatment in the outpatient or hospital setting and disease sequelae were extracted from the published literature. The main outcome of the analysis was quality-adjusted life-years (QALYs).ResultsThe vaccines had incremental cost-utility ratios ranging from USD 4,121 (Oxford) to USD 3,160 per QALY (CoronaVac). The older the population, the lower the incremental cost-utility ratio. Given a willingness-to-pay threshold of BRL 3,129 per QALY, all the vaccines were considered cost effective in the probabilistic sensitivity analysis. The incremental cost-effectiveness ratio stratified by age ranged from USD 6,327 per QALY in patients older than 75 years (Janssen) to USD 20,993 per QALY in patients younger than 59 years (CoronaVac).ConclusionsThe results of this analysis, stratified by patient age, can help in the preparation of a vaccination prioritization plan.

Potential use of the S-protein-Angiotensin converting enzyme 2 binding pathway in the treatment of coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), infects humans through a strong interaction between the viral spike protein (S-protein) and angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. The infection of host lung cells by SARS-CoV-2 leads to clinical symptoms in patients. However, ACE2 expression is not restricted to the lungs; altered receptors have been found in the nasal and oral mucosa, vessel, brain, pancreas, gastrointestinal tract, kidney, and heart. The future of COVID-19 is uncertain, however, new viral variants are likely to emerge. The SARS-CoV-2 Omicron variant has a total of 50 gene mutations compared with the original virus; 15 of which occur in the receptor binding domain (RBD). The RBD of the viral S-protein binds to the human ACE2 receptor for viral entry. Mutations of the ACE2-RBD interface enhance tight binding by increasing hydrogen bond interactions and expanding the accessible surface area. Extracorporeal membrane oxygenation, hyperbaric oxygen, and aggressive dialysis for the treatment of COVID-19 have shown various degrees of clinical success. The use of decoy receptors based on the ACE2 receptor as a broadly potent neutralizer of SARS-CoV-2 variants has potential as a therapeutic mechanism. Drugs such as 3E8 could block binding of the S1-subunit to ACE2 and restrict the infection of ACE2-expressing cells by a variety of coronaviruses. Here, we discuss the development of ACE2-targeted strategies for the treatment and prevention of COVID-19.

Clinical Chemistry and Laboratory Medicine celebrates 60 years- narrative review devoted to the contribution of the journal to the diagnosis of SARS-CoV-2.

This review is an integral part of the special issue for the 60 years of the journal Clinical Chemistry and Laboratory Medicine (CCLM). The aim of the review is to highlight the role of the clinical laboratory since the emergence of the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), which causes Coronavirus disease 2019 (COVID-19), with special focus on the contribution of the journal in generating knowledge in SARS-CoV-2 diagnosis. As of October 30, 2022, a total of 186 CCLM publications were dedicated to COVID-19. Of importance, major International Federation of Clinical Chemistry (IFCC) guidelines related to the diagnosis of COVID-19 were published in CCLM. Between early-2020 and late October 2022, COVID-19 publications represented around 27% of all articles in CCLM, highlighting the willingness of the editorial board to help the field in order to better describe and diagnose this new emerging disease. First launched in 1963 under the name "Zeitschrift für Klinische Chemie", the Journal was entirely devoted to clinical chemistry in the strict sense. The various topics published in relation to COVID-19 including its diagnosis, its impact on biochemical or hematological measures, as well as biosafety measures, is the perfect example that shows that the journal has greatly diversified over time.

Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.

Associations between SARS-CoV-2 infections and thrombotic complications necessitating surgical intervention: A systematic review.

Several unique clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19) infection, have been identified and characterized. One such feature, mostly among patients with severe COVID-19 infection, has become known as COVID-19-induced coagulopathy. Surgical patients with a history of or active COVID-19 infection bear a significantly higher risk for postoperative thrombotic complications. These patients may require surgical intervention to treat severe thrombotic complications. Few studies have been carried out to better characterize this association. The purpose of this study was to perform a systematic review and meta-analysis of the literature on COVID-19 infections that led to thrombotic complications necessitating surgical intervention. We hypothesized that patients with recent or active COVID-19 infection would have high rates of thromboembolic complications both arterial and venous in origin. To perform a systematic review and meta-analysis of the literature on COVID-19 infections that led to thrombotic complications necessitating surgical intervention. The current systematic review implemented an algorithmic approach to review all the currently available English medical literature on surgical interventions necessitated by COVID-19 thrombotic complications using the preferred reporting items for systematic reviews and meta-analysis principles. A comprehensive search of the medical literature in the "PubMed", "Scopus", "Google Scholar" top 100 results, and archives of Plastic and Reconstructive Surgery was performed using the key words "COVID-19" AND "surgery" AND "thromboembolism" AND "complication". The search string was generated and the records which were not specific about surgical interventions or thrombotic complications due to COVID-19 infection were excluded. Titles and abstracts were screened by two authors and full-text articles were assessed for eligibility and inclusion. Finally, results were further refined to focus on articles that focused on surgical interventions that were necessitated by COVID-19 thrombotic complications. The database search resulted in the final inclusion of 22 retrospective studies, after application of the inclusion/exclusion criteria. Of the included studies, 17 were single case reports, 3 were case series and 2 were cross sectional cohort studies. All studies were retrospective in nature. Twelve of the reported studies were conducted in the United States of America, with the remaining studies originating from Italy, Turkey, Pakistan, France, Serbia, and Germany. All cases reported in our study were laboratory confirmed SARS-CoV-2 positive. A total of 70 cases involving surgical intervention were isolated from the 22 studies included in this review. There is paucity of data describing the relationship between COVID-19 infection and thrombotic complications necessitating the need for surgical intervention. Intestinal ischemia and acute limb ischemia are amongst the most common thrombotic events due to COVID-19 that required operative management. An overall postoperative mortality of 30% was found in those who underwent operative procedures for thrombotic complications, with most deaths occurring in those with bowel ischemia. Physicians should be aware that despite thromboprophylaxis, severe thrombotic complications can still occur in this patient population, however, surgical intervention results in relatively low mortality apart from cases of ischemic bowel resection.

Insights on the possibility of SARS-CoV-2 transmission through the eyes.

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCOV), causing coronavirus disease 2019 (COVID-19), has rapidly spread to most countries and regions worldwide since it broke out at the end of 2019. Epidemic of the virus produces a tremendous pressure on the global health systems. With progressive insight into SARS-CoV-2, the role of eye tissue has attracted wide attention in the spread of COVID-19. Whether SARS-CoV-2 can enter the human body through eyes and cause infection? The fact that unprotected exposure of the eyes to 2019-nCoV might have allowed the virus to infect the body implies that 2019-nCOV can invade eye tissue and set foot in organism. Facing the severe challenge of preventing spread of the COVID-19, combined with the high-risk environment of ophthalmology, it is crucial to investigate ocular tropism of coronavirus. This paper explores the possibility of coronavirus transmission through the eye from aspects of probable mechanisms, clinical cases, detection of coronavirus; and puts forward precautions for ophthalmologists and nurses. Consequently, this review reveals our understanding of ocular tropism of coronavirus and contributes to determining risk of ocular transmission, raising awareness of necessary eye protection among medical workers and reducing further prevalence of SARS-CoV-2.

Calibrated bagging deep learning for image semantic segmentation: A case study on COVID-19 chest X-ray image.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Imaging tests such as chest X-ray (CXR) and computed tomography (CT) can provide useful information to clinical staff for facilitating a diagnosis of COVID-19 in a more efficient and comprehensive manner. As a breakthrough of artificial intelligence (AI), deep learning has been applied to perform COVID-19 infection region segmentation and disease classification by analyzing CXR and CT data. However, prediction uncertainty of deep learning models for these tasks, which is very important to safety-critical applications like medical image processing, has not been comprehensively investigated. In this work, we propose a novel ensemble deep learning model through integrating bagging deep learning and model calibration to not only enhance segmentation performance, but also reduce prediction uncertainty. The proposed method has been validated on a large dataset that is associated with CXR image segmentation. Experimental results demonstrate that the proposed method can improve the segmentation performance, as well as decrease prediction uncertainty.

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19

BackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which is currently a worldwide pandemic. There are limited available treatments for severe COVID-19 patients. However, some evidence suggests that intravenous immunoglobulin (IVIg) provides clinical benefits for these patients.MethodsWe administered IVIg to 23 severe COVID-19 patients, and all of them survived. Four related coronaviruses can cause the common cold. We speculated that cross-reactivity of SARS-CoV-2 and other common coronaviruses might partially explain the clinical efficacy of IVIg therapy. Thus, we performed multiple alignment analysis of the spike (S), membrane (M), and nucleotide (N) proteins from SARS-CoV-2 and the common coronaviruses to identify conserved regions. Next, we synthesized 25 peptides that were conserved regions and tested their IVIg seropositivity.ResultsThe results indicated four peptides had significant or nearly significant seropositivity, and all of them were associated with the S and M proteins. Examination of the immune responses of healthy volunteers to each synthetic peptide indicated high seropositivity to the two peptides from S protein. Blood samples from healthy individuals may have pre-existing anti-SARS-CoV-2 IgGs, and IVIg is a potentially effective therapy for severe COVID-19.ConclusionIn conclusion, blood samples from many healthy individuals have pre-existing anti-SARS-CoV-2 IgGs, and IVIg may be an effective therapy for severe COVID-19.

An Updated Review on Complicated Mechanisms of COVID-19 Pathogenesis and Therapy: Direct Viral Damage, Renin-angiotensin System Dysregulation, Immune System Derangements, and Endothelial Dysfunction.

SARS-CoV-2 was reported as the cause of coronavirus disease 2019 (COVID-19) in late December 2019. According to sequencing and phylogenetic studies, the new virus belongs to Coronaviridae family and Betacoronavirus genus. Genomic sequence analysis has shown SARS-CoV-2 to be similar to SARS. SARS-CoV-2 is more infectious, and the high level of COVID-19 community transmission has led to a growing pandemic. Although infections in most patients with COVID-19 are moderate or mild, 20% of the patients develop a severe or critical form of the disease. COVID-19 may affect a wide range of organs and tissues, including the respiratory system, digestive system, nervous system, and skin. Patients with COVID-19 have been confirmed to have renal, cardiovascular, gastrointestinal, and nervous system problems in addition to pulmonary involvement. The pathogenesis of SARS-CoV-2 is being investigated, but it is possible that the organ damage might in part be caused by direct viral damage (detection of inclusion bodies in tissues, such as the kidneys), dysregulation of the immune system, renin-angiotensin system, bradykinin pathway, and coagulation, as well as host genetic factors and their polymorphisms, which may affect the disease severity. In this review, an update on the possible pathogenesis pathways of COVID-19 has been provided. It is hoped that the best care strategy will be developed for patients with COVID-19 by identifying its pathogenesis pathways.

Retrospective Analysis of the SARS-CoV-2 Infection Profile in COVID-19 Positive Patients in Vitoria da Conquista, Northeast Brazil.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for causing Coronavirus Disease-2019 (COVID-19), a heterogeneous clinical condition that manifests varying symptom severity according to the demographic profile of the studied population. While many studies have focused on the spread of COVID-19 in large urban centers in Brazil, few have evaluated medium or small cities in the Northeast region. The aims of this study were: (i) to identify risk factors for mortality from SARS-CoV-2 infection, (ii) to evaluate the gene expression patterns of key immune response pathways using nasopharyngeal swabs of COVID-19 patients, and (iii) to identify the circulating SARS-CoV-2 variants in the residents of a medium-sized city in Northeast Brazil. A total of 783 patients infected with SARS-CoV-2 between May 2020 and August 2021 were included in this study. Clinical-epidemiological data from patients who died and those who survived were compared. Patients were also retrospectively divided into three groups based on disease severity: asymptomatic, mild, and moderate/severe. Samples were added to a qPCR array for analyses of 84 genes involved with immune response pathways and sequenced using the Oxford Nanopore MinION technology. Having pre-existing comorbidity; being male; having cardiovascular disease, diabetes, and/or chronic obstructive pulmonary disease; and PCR cycle threshold (Ct) values under 22 were identified as risk factors for mortality. Analysis of the expression profiles of inflammatory pathway genes showed that the greater the infection severity, the greater the activation of inflammatory pathways, triggering the cytokine storm and downregulating anti-inflammatory pathways. Viral genome analysis revealed the circulation of multiple lineages, such as B.1, B.1.1.28, Alpha, and Gamma, suggesting that multiple introduction events had occurred over time. This study's findings help identify the specific strains and increase our understanding of the true state of local health. In addition, our data demonstrate that epidemiological and genomic surveillance together can help formulate public health strategies to guide governmental actions.

Hubungan Pengetahuan Tentang Virus Dan Kepatuhan Prokes 5-M Siswa

In the verse of Yaseen 36 it is written that there is something unknwon to people at the time. Today we know there is supermicroorganism - that is virus. Virus is the cause of some infection like what happened since early 2020 when the pandemy occurred. The virus is beta-coronavirus novel. This is the new type of corona. It is the cause of Coronavirus Disease 2019 (Covid-19).
 Some efforts to overcome the disease includes health protocol such as 5 M in Bahasa Indonesia (wearing mask, washing hands, physical distancing, avoiding crowd, and limiting mobility). Implementation of the health protocol is limited when the public does not support. Public compliance to the policy is influenced by several factors like age and education. The objective of the research is to find out the corelation betweeen knowledge about Covid-19 with compliance to health protocol (5M). I use methodes of survey by filling out questionnaire to students of SMP Islam Al Aszar 10, Kembangan, Jakarta. The result is calculated by using linier equation between knowledge and compliance.
 Intercept (a)= 60,34641; slope (b)= 0,358306 and corelation (r)= 0,949393. X is knowledge and Y is complaince. From the research we come to a conlusion that some knowledge is still lacking like the life of virus, prevention of cantagion, the size of virus and covid-19. But they comply woth the health protocol of 5 M, seen from slope 0,358306. Although knwledge (X) is low , Y (compliance) high almost the same .
 It is because the government, the school and the researcher have given some informations about the importance of health protocol of 3 M and now 5 M.

Inosine: A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19 (COVID-19) progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies are frequently administered to treat COVID-19, but have limited clinical efficacy in severe and critical cases. Nevertheless, the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection. We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin (IL)-6, upregulated anti-inflammatory IL-10, and ameliorated acute inflammatory lung injury caused by multiple infectious agents. Inosine significantly improved survival in mice infected with SARS-CoV-2. It indirectly impeded TANK-binding kinase 1 (TBK1) phosphorylation by binding stimulator of interferon genes (STING) and glycogen synthase kinase-3β (GSK3β), inhibited the activation and nuclear translocation of the downstream transcription factors interferon regulatory factor (IRF3) and nuclear factor kappa B (NF-κB), and downregulated IL-6 in the sera and lung tissues of mice infected with lipopolysaccharide (LPS), H1N1, or SARS-CoV-2. Thus, inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19. Moreover, targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

SARS-CoV-2 cellular tropism and direct multiorgan failure in COVID-19 patients: Bioinformatic predictions, experimental observations, and open questions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has led to an unprecedented public health emergency worldwide. While common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. Organ damage in COVID-19 patients is partially associated with the indirect effects of SARS-CoV-2 infection (e.g., systemic inflammation, hypoxic-ischemic damage, coagulopathy), but early processes in COVID-19 patients that trigger a chain of indirect effects are connected with the direct infection of cells by the virus. To understand the virus transmission routes and the reasons for the wide-spectrum of complications and severe outcomes of COVID-19, it is important to identify the cells targeted by SARS-CoV-2. This review summarizes the major steps of investigation and the most recent findings regarding SARS-CoV-2 cellular tropism and the possible connection between the early stages of infection and multiorgan failure in COVID-19. The SARS-CoV-2 pandemic is the first epidemic in which data extracted from single-cell RNA-seq (scRNA-seq) gene expression data sets have been widely used to predict cellular tropism. The analysis presented here indicates that the SARS-CoV-2 cellular tropism predictions are accurate enough for estimating the potential susceptibility of different cells to SARS-CoV-2 infection; however, it appears that not all susceptible cells may be infected in patients with COVID-19.