Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms.

BACKGROUND: Autoimmunity has been reported in patients with severe COVID-19. We investigated whether antinuclear/extractable-nuclear antibodies (ANAs) were present up to a year after infection, and if they were associated with the development of clinically relevant Post-Acute Sequalae of COVID-19 (PASC) symptoms. METHODS: A rapid assessment line immunoassay was used to measure circulating levels of ANA/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6, and 12 months post-recovery. Patient-reported fatigue, cough, and dyspnea were recorded at each timepoint. Multivariable logistic regression model and receiver-operating curves (ROC) were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines. RESULTS: Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased from 3 to 12 months (3.99 to 1.55) with persistent positive titers associated with fatigue, dyspnea, and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, AUC=0.86) and dyspnea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNFα) and C-reactive protein predicted the elevated ANAs at 12 months. TNFα, D-dimer, and IL-1ß had the strongest association with symptoms at 12 months. Regression analysis showed TNFα predicted fatigue (ß=4.65, p=0.004) and general symptomaticity (ß=2.40, p=0.03) at 12 months. INTERPRETATION: Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNFα) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.

Hospitalised COVID-19 outcomes are predicted by hypoxaemia and pneumonia phenotype irrespective of the timing of their emergence.

Despite the known clinical importance of hypoxemia and pneumonia, there is a paucity of evidence for these variables with respect to risk of mortality and short-term outcomes among those hospitalised with COVID-19. OBJECTIVE: Describe the prevalence and clinical course of patients hospitalised with COVID-19 based on oxygenation and pneumonia status at presentation and determine the incidence of emergent hypoxaemia or radiographic pneumonia during admission. METHODS: A retrospective study was conducted using a Canadian regional registry. Patients were stratified according to hypoxaemia/pneumonia phenotype and prevalence. Clinical parameters were compared between phenotypes using χ2 and one-way Analysis of variance (ANOVA). Cox analysis estimated adjusted Hazard Ratios (HR) for associations between disease outcomes and phenotypes. RESULTS: At emergency department (ED) admission, the prevalence of pneumonia and hypoxaemia was 43% and 50%, respectively, and when stratified to phenotypes: 28.2% hypoxaemia+/pneumonia+, 22.2% hypoxaemia+/pneumonia-, 14.5% hypoxaemia-/pneumonia+ and 35.1% hypoxaemia-/pneumonia-. Mortality was 31.1% in the hypoxaemia+/pneumonia- group and 26.3% in the hypoxaemia+/pneumonia+ group. Hypoxaemia with pneumonia and without pneumonia predicted higher probability of death. Hypoxaemia either <24 hours or ≥24 hours after hospitalisation predicted higher mortality and need for home oxygen compared with those without hypoxaemia. Patients with early hypoxaemia had higher probability of Intensive care unit (ICU) admission compared with those with late hypoxaemia. CONCLUSION: Mortality in COVID-19 infection is predicted by hypoxaemia with or without pneumonia and was greatest in patients who initially presented with hypoxaemia. The emergence of hypoxaemia was predicted by radiographic pneumonia. Patients with early and emergent hypoxaemia had similar mortality but were less likely to be admitted to ICU. There may be delayed identification of hypoxaemia, which prevents timely escalation of care.