New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in [~]25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed de novo following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.