COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.

This paper provides a model for developing protocols to allow high quality comparative research on relationships between the environment and physical activity and other outcomes of public health interest.

IMPORTANCE Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the United States are still emerging. OBJECTIVE To elucidate SARS-CoV-2 seroprevalence and symptom onset in a culturally linked community across 5 states in the United States. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included adults (aged Ն18 years) recruited from the orthodox Jewish community across 5 states (California, Connecticut, Michigan, New Jersey, and New York) in 3 geographically distinct areas of the United States between May 13 and July 6, 2020. Participants completed an online survey and underwent SARS-CoV-2 antibody testing. MAIN OUTCOMES AND MEASURES Seroprevalence and date of symptom onset of SARS-CoV-2. RESULTS Overall, 9507 adults (mean [SD] age, 39.6 [15.0] years; 3777 [39.7%] women) completed the SARS-CoV-2 survey, of whom 6665 (70.1%) had immunoglobin G anti-SARS-CoV-2 antibody levels assessed. A high seroprevalence of SARS-CoV-2 antibodies was observed across all communities, with the highest proportion of positive testing observed in New Jersey (1080 of 3323 [32.5%]) and New York (671 of 2196 [30.6%]). Most individuals with a positive SARS-CoV-2 immunoglobin G antibody test reported a date of symptom-onset between March 9 and March 31,

Background The complex relationship between clinical manifestations of SARS-CoV-2 and individual immune responses is not fully elucidated. Objective To examine phenotypes of symptomatology and their relationship with positive anti-SARS-CoV-2 IgG antibody responses. Methods An observational study was performed of adults (≥18 years) from 5 US states. Participants completed an electronic survey and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody between May-July 2020. Latent Class Analysis was used to identify characteristic symptom clusters. Results Overall, 9,507 adults (mean±SD age: 39.6±15.0 years) completed the survey; 6,665 (70.1%) underwent antibody testing for anti-SARS-CoV-2 IgG. Positive SARS-CoV-2 antibodies were associated with self-reported positive SARS-CoV-2 nasal swab (bivariable logistic regression; OR [CI95]: 5.98 [4.83, 7.41]), household with ≥6 members (1.27 [1.14, 1.41]) and sick contact (3.65 [3.19, 4.17]), and older age (50-69 years: 1.55 [1.37, 1.76]); ≥70 years: 1.52 [1.16, 1.99]), but inversely associated with female sex (0.61 [0.55, 0.68]). Latent class analysis revealed 8 latent classes of symptoms. Latent classes-1 (all symptoms) and 4 (fever, cough, muscle ache, anosmia, dysgeusia, and headache) were associated with the highest proportion (62.0% and 57.4%) of positive antibodies, whereas classes-6 (fever, cough, muscle ache, headache) and 8 (anosmia, dysgeusia) had intermediate proportions (48.2% and 40.5%), and classes-3 (headache, diarrhea, stomach pain) and 7 (no symptoms) had the lowest proportion (7.8% and 8.5%) of positive antibodies. Conclusion SARS-CoV-2 infections manifest with substantial diversity of symptoms, which are associated with variable anti-SARS-CoV-2 IgG antibody responses. Prolonged fever, anosmia and receiving supplemental oxygen therapy had strongest associations with positive SARS-CoV-2 IgG.

Background: COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery—a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies. Aim and methods: To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid β peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]). Results: COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid β peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and α-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid β peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome. Conclusions: Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients