Long-Term Symptom Profiles After Covid-19 Vs Other Acute Respiratory Infections: a Population-Based Observational Study

Abstract

Introduction and Objectives Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms. Methods COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data on 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported in January, 2021, by participants unvaccinated against SARS-CoV-2. Symptoms analysed were coughing, sleep problems, memory problems, difficulty concentrating, muscle or joint pain, problems with sense of taste/smell, diarrhoea, stomach problems, changes to voice, hair loss, unusual racing of the heart, lightheadedness or dizziness, unusual sweating, breathlessness, anxiety or depression, and fatigue. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (>=4 weeks prior) or no reported ARIs. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). Findings We included 10,203 participants (1343 13.2%] with SARS-CoV-2 infection, 472 4.6%] with non-COVID-19 ARI). When compared with no infection, both SARS-CoV-2 and non-COVID-19 ARIs were associated with increased prevalence or severity of most symptoms and decreased HRQoL. When comparing infection types, participants with SARS-CoV- 2 infection had higher odds of taste/smell problems (odds ratio 8.06, 95% CI 4.52-14.35) and hair loss (2.10, 1.39- 3.19) than participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. For SARS-CoV-2, the most severe group was characterised by an increase in overall symptom burden, with the greatest differences in memory problems, difficulty concentrating, and lightheadedness or dizziness. When comparing the most severe groups by infection status, SARS-CoV-2 infection presented with a higher probability of memory problems, difficulty concentrating, hair loss, and taste/smell problems than non-COVID-19 ARI. Conclusions Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of long-term symptoms. Research on post-acute sequelae of ARIs should extend from SARSCoV- 2 to include other pathogens.