Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78–3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50–4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68–3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47–2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02–3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29–3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26–4.36), Behçet's disease (aHR:2.32, 95% CI:1.38–3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36–3.57), vasculitis (aHR:1.96, 95% CI:1.74–2.20), psoriasis (aHR:2.91, 95% CI:2.67–3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72–1.84), celiac disease (aHR:2.68, 95% CI:2.51–2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51–2.85) and mortality (aHR:1.20, 95% CI:1.16–1.24).

Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.

Plausible, need to reread.

June 2023

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6–89.6) and 642.8 (95% CI: 596.9–689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9–31.0%) and 21.3% (18.2–24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection.