Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study

Abstract:

Background: The burden and duration of persistent symptoms after non-severe COVID-19 remains uncertain. This study aimed to assess post-infection symptom trajectories in home-isolated COVID-19 cases compared to age- and time-period matched seronegative controls, and investigate immunological correlates of long COVID.

Methods: A prospective case-control study conducted between February 28th and April 4th 2020 included home-isolated COVID-19 cases followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched SARS-CoV-2 naive controls. We collected clinical data at baseline, 6, 12 and 18 months post-infection, and blood samples at 2, 4, 6 and 12 months for analysis of SARS-CoV-2 specific humoral and cellular responses.

Results: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared to controls, adult cases had a high risk of fatigue (27% excess risk, gender and comorbidity adjusted odds ratio [aOR] 5.86, 95% confidence interval [CI]3.27-10.5), memory problems (21% excess risk, aOR 7.42, CI 3.51-15.67), concentration problems (20% excess risk, aOR 8.88, CI 3.88-20.35), and dyspnea (10% excess risk, aOR 2.66, CI 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%, CI 1.5, 21.5, p = 0.024) and among women (excess risk 18.7%, CI 4.4, 32.9, p = 0.010). Longitudinal spike IgG was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4 + TCRβ depth was significantly associated with both dyspnea and number of symptoms at 12 months.

Conclusions: This study documents a high burden of persisting symptoms after mild COVID-19, and suggest that infection induced SARS-CoV-2 specific immune responses may influence long-term symptoms.

Source: Fjelltveit EB, Blomberg B, Kuwelker K, Zhou F, Onyango TB, Brokstad KA, Elyanow R, Kaplan IM, Tøndel C, Mohn KGI, Özgümüş T, Cox RJ, Langeland N; Bergen COVID-19 Research Group. Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study. Clin Infect Dis. 2022 Aug 12:ciac655. doi: 10.1093/cid/ciac655. Epub ahead of print. PMID: 35959897; PMCID: PMC9384725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384725/ (Full text)

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