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Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS., (© 2022. The Author(s).)

Background: Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear., Objectives: Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases., Methods: Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109)., Results: SARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age., Conclusions: Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: T‐cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID‐19). How T‐cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. Methods: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID‐19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40‐parameter mass cytometry, targeted proteomics, and functional assays. Results: The extensive T‐cell lymphopenia observed particularly in patients with severe COVID‐19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T‐cell responses to common viral antigens. We detected persisting CD4+ and CD8+ T‐cell activation up to 12 months after infection, in patients with mild and severe COVID‐19, as measured by increased HLA‐DR and CD38 expression on these cells. Persistent T‐cell activation after COVID‐19 was independent of administration of a COVID‐19 vaccine post‐infection. Furthermore, we identified a subgroup of patients with severe COVID‐19 that presented with persistently low CD8+ T‐cell counts at follow‐up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T‐cell response and signs of excessive pro‐inflammatory cytokine production. Conclusion: Our study suggests that T‐cell numbers and function recover in most patients after COVID‐19. However, we find evidence of persistent T‐cell activation up to 12 months after infection and describe a subgroup of severe COVID‐19 patients with persistently low CD8+ T‐cell counts exhibiting a dysregulated immune response during acute infection. [ABSTRACT FROM AUTHOR]

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID‐19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID‐19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome‐wide serological profiling in a multicentric cohort of 175 COVID‐19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID‐19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID‐19. Furthermore, patients with severe COVID‐19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS‐CoV‐2‐specific antibody titers in COVID‐19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen‐specific humoral responses. Notably, the qualitative breadth of antibodies cross‐reactive with other coronaviruses was comparable in ANA‐positive and ANA‐negative individuals during acute COVID‐19. In autoantibody‐positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID‐19 and alterations of the B‐cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS‐CoV‐2 infection, while the presence of autoantibodies in COVID‐19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures. [ABSTRACT FROM AUTHOR]

Among people infected with SARS-CoV-2, the determination of clinical features associated with poor outcome is essential to identify those at high risk of deterioration. Here, we aimed to investigate clinical phenotypes of patients hospitalized due to COVID-19 and to examine the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in a representative patient collective of the Swiss population. We conducted a retrospective monocentriccohort study with patients hospitalized due to COVID-19 between 27 February and 31 December 2020. Data were analyzed descriptively, using the binary logistic regression model, proportional odds logistic regression model, competing risk analysis, and summary measure analysis. A total of 454 patients were included in our study. Dyspnea, elevated respiratory rate, low oxygen saturation at baseline, age, and presence of multiple comorbidities were associated with a more severe course of the disease. A high NLR at baseline was significantly associated with disease severity, unfavorable outcome, and mortality. In non-survivors, NLR further increased during hospital stay, whereas in survivors, NLR decreased. In conclusion, our data emphasize the importance of accurate history taking and clinical examination upon admission and confirm the role of baseline NLR as a surrogate marker for increased disease severity, unfavorable outcome, and mortality in patients hospitalized due to infection with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID‐19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill‐defined in COVID‐19. Methods: We prospectively enrolled individuals with mild and severe COVID‐19 into our multicenter cohort and performed a cross‐sectional analysis of phenotypic and functional characteristics of T cells using 40‐parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. Results: Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID‐19. Individuals with severe COVID‐19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin‐7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. Conclusion: Our study suggests that severe COVID‐19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery. [ABSTRACT FROM AUTHOR]