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A previous report demonstrated the strong association between the presence of antibodies binding to an epitope region from SARS-CoV-2 nucleocapsid, termed Ep9, and COVID-19 disease severity. Patients with anti-Ep9 antibodies (Abs) had hallmarks of antigenic interference (AIN), including early IgG upregulation and cytokine-associated injury. Thus, the immunological memory of a prior infection was hypothesized to drive formation of suboptimal anti-Ep9 Abs in severe COVID-19 infections. This study identifies a putative primary antigen capable of stimulating production of cross-reactive, anti-Ep9 Abs. Binding assays with patient blood samples directly show cross-reactivity between Abs binding to Ep9 and only one bioinformatics-derived, homologous putative antigen, a sequence derived from the neuraminidase protein of H3N2 influenza A virus. This cross-reactive binding is highly influenza strain specific and sensitive to even single amino acid changes in epitope sequence. The neuraminidase protein is not present in the influenza vaccine, and the anti-Ep9 Abs likely resulted from the widespread influenza infection in 2014. Therefore, AIN from a previous infection could underlie some cases of COVID-19 disease severity., Competing Interests: The authors have declared that no competing interests exist.

Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients ( n  = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient's comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity., (Copyright © 2021 Sen et al.)

Background: Health-care workers (HCWs) in India have been heavily impacted by the COVID-19 pandemic, facing significant psychological distress due to their challenging work, exposure to the virus, and isolation. This study examines the emotional states and coping strategies of HCWs and the potential effects of religious coping mechanisms on their mental health. Aim: To explore the emotional state, coping strategies, and impact of religious beliefs on the mental health of junior doctors in a COVID-19-designated tertiary care hospital in Mysore. Methods: The cross-sectional survey-based observational study included residents and house surgeons working in COVID-19 wards. Sociodemographic data along with their emotional state and coping strategies were assessed using Depression, Anxiety, and Stress Scale-21 (DASS-21), Brief COPE Inventory, and the Brief Religion COPE. Chi-square test and Pearson’s correlation were used to evaluate the relationship between variables. Results: Majority (57.2%) of the participants were between 21 and 25 years and of male gender (61.6%), with Hinduism being the most prevalent religious affiliation (88.4%). Most (71.7%) tested positive for COVID-19. A significant prevalence of stress, anxiety, and depression among HCWs. Significant associations were found between stress, anxiety, and factors such as living alone, working in emergency care, substance use, and associations between religious coping and emotional status. Conclusion: The study highlighted the psychological distress faced by HCWs during the COVID-19 pandemic and proposes that religious coping techniques may help their mental health amid emergencies. Promoting an integrated strategy that incorporates psychological and religious coping mechanisms may improve health-care personnel’s overall resilience and mental well-being in the face of future challenges.