Detection of Antinuclear Antibodies Targeting Intracellular Signal Transduction, Metabolism, Apoptotic Processes and Cell Death in Critical COVID-19 Patients.

Background and Objectives: The heterogeneity of the coronavirus disease of 2019 (COVID-19) lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) is a leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Results: Initial screening for antinuclear antibodies (ANA) IgG using ELISA revealed that 1.58% (2/126) and 4% (5/126) of intensive care unit (ICU) COVID-19 cases expressed strong and moderate ANA levels, respectively. An additional sample was positive with immunofluorescence assays (IFA) screening. However, all the non-ICU cases (n=273) were ANA negative using both assays. Samples positive for ANA were further confirmed with large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). The majority of the ANA-positive samples showed "speckled" ANA pattern by microscopy and revealed autoantibody specificities that targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death by PhIP-Seq; further denoting reactivity to nuclear and cytoplasmic antigens. Conclusion: Our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of COVID-19.

Immunoinformatics prediction of potential immunodominant epitopes from human coronaviruses and association with autoimmunity.

Cross-reactivity between different human coronaviruses (HCoVs) might contribute to COVID-19 outcomes. Here, we aimed to predict conserved peptides among different HCoVs that could elicit cross-reacting B cell and T cell responses. Three hundred fifty-one full-genome sequences of HCoVs, including SARS-CoV-2 (51), SARS-CoV-1 (50), MERS-CoV (50), and common cold species OC43 (50), NL63 (50), 229E (50), and HKU1 (50) were downloaded aligned using Geneious Prime 20.20. Identification of epitopes in the conserved regions of HCoVs was carried out using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. Further, we identified sequences that bind multiple common MHC and modeled the three-dimensional structures of the protein regions. The search yielded 73 linear and 35 discontinuous epitopes. A total of 16 B-cell and 19 T-cell epitopes were predicted through a comprehensive bioinformatic screening of conserved regions derived from HCoVs. The 16 potentially cross-reactive B-cell epitopes included 12 human proteins and four viral proteins among the linear epitopes. Likewise, we identified 19 potentially cross-reactive T-cell epitopes covering viral proteins. Interestingly, two conserved regions: LSFVSLAICFVIEQF (NSP2) and VVHSVNSLVSSMEVQSL (spike), contained several matches that were described epitopes for SARS-CoV. Most of the predicted B cells were buried within the SARS-CoV-2 protein regions' functional domains, whereas T-cell stretched close to the functional domains. Additionally, most SARS-CoV-2 predicted peptides (80%) bound to different HLA types associated with autoimmune diseases. We identified a set of potential B cell and T cell epitopes derived from the HCoVs that could contribute to different diseases manifestation, including autoimmune disorders.

Reinfections in COVID-19 Patients: Impact of Virus Genetic Variability and Host Immunity.

The COVID-19 pandemic is still posing a devastating threat to social life and economics. Despite the modest decrease in the number of cases during September-November 2020, the number of active cases is on the rise again. This increase was associated with the emergence and spread of the new SARS-CoV-2 variants of concern (VOCs), such as the U.K. (B1.1.7), South Africa (B1.351), Brazil (P1), and Indian (B1.617.2) strains. The rapid spread of these new variants has raised concerns about the multiple waves of infections and the effectiveness of available vaccines. In this review, we discuss SARS-CoV-2 reinfection rates in previously infected and vaccinated individuals in relation to humoral responses. Overall, a limited number of reinfection cases have been reported worldwide, suggesting long protective immunity. Most reinfected patients were asymptomatic during the second episode of infection. Reinfection was attributed to several viral and/or host factors, including (i) underlying immunological comorbidities; (ii) low antibody titers due to the primary infection or vaccination; (iii) rapid decline in antibody response after infection or vaccination; and (iv) reinfection with a different SARS-CoV-2 variant/lineage. Infections after vaccination were also reported on several occasions, but mostly associated with mild or no symptoms. Overall, findings suggest that infection- and vaccine-induced immunity would protect from severe illness, with the vaccine being effective against most VOCs.

Markers Associated with COVID-19 Susceptibility, Resistance, and Severity.

In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.