Retrospective Cohort; Prospective Cohort
Study population and setting
This longitudinal study included healthcare workers at Danderyd Hospital in Stockholm, Sweden who were enrolled between April 15 and May 8, 2020. Blood samples, which were obtained at baseline and prospectively collected every four months thereafter, were analyzed for SARS-CoV-2 IgG antibodies, reflecting previous infection. Participants reported demographics, COVID-19 symptoms, and COVID-19 severity at baseline and again after 8 months of follow-up, when they described the duration of symptoms (<2 months, 2 months or more, 4 months or more, and 8 months or more) and severity (mild, moderate, severe) for 23 predefined symptoms. Individuals with detectable SARS-CoV-2 IgG antibodies at baseline who reported severe symptoms were excluded, as were individuals who were initially seronegative but converted during follow-up. Among the 2149 participants initially enrolled, only 1395 were included in the analysis, including 323 who were seropositive for SARS-CoV-2 IgG antibodies at baseline and 1072 who were seronegative. Exclusion reasons were: severe symptoms reported at baseline (n=50), seroconverted during follow-up (n=404), and did not complete 8 month follow-up (n=300; 20 seropositive and 280 seronegative).
Summary of Main Findings
Seropositive and seronegative individuals were relatively similar with regard to age (median age: 43 years vs. 47 years), sex (84% female vs. 83% female), and prevalence of underlying chronic diseases (22% vs. 24%). Overall, 26%, 21%, and 15% of seropositive individuals reported at least 1 moderate to severe symptom lasting at least two, four, or eight months, respectively, compared to only 9%, 7% and 3% of seronegative individuals. Seropositive individuals had 4.4 times the risk of having moderate to severe long-term symptoms lasting at least 8 months, compared to seronegative individuals (RR=4.4, 95% CI: 2.9-6.7). For seropositive individuals (vs. seronegative individuals), the most common moderate or severe symptoms at 8 months or later were anosmia (loss of smell; 9% vs. 0.1%), fatigue (4% vs. 1.5%), ageusia (loss of taste; 3.7% vs. 0.1%), and dyspnea (shortness of breath; 1.9% vs. 0.3%). Seropositive patients (vs. seronegative patients) were additionally more likely to report moderate-to-marked disruptions to work life (8% vs. 4%), social life (15% vs. 6%), and home life (12% vs. 5%).
This study longitudinally followed individuals for more than 8 months, regardless of SARS-CoV-2 infection status, allowing for estimation of the excess population-level prevalence of long-term symptoms due to COVID-19.
Symptom duration and severity during follow-up were retrospectively self-reported, which may have resulted in a higher reporting of more severe symptoms among people who knew they previously had COVID-19. It is additionally possible that some individuals in the seronegative group had had COVID-19 but did not have detectable SARS-CoV-2 IgG antibodies during follow-up, resulting in misclassification of their exposure. The resultant bias would likely be towards the null, leading to stronger associations between SARS-CoV-2 seropositivity and long-term symptoms, unless individuals with falsely negative antibody tests had milder symptoms. Additionally, 6% of seropositive individuals and 20% of seronegative individuals did not complete follow-up, which may have resulted in some selection bias. Similarly, differential participation may have induced bias in an unpredictable direction; for example, if seronegative individuals with long-term symptoms due to other conditions were more likely to participate than seronegative individuals without any long-term symptoms, this could bias the results toward the null. All analyses were unadjusted, and despite comparability between seropositive and seronegative individuals on several baseline characteristics, residual confounding is likely and caution is warranted interpreting the relative risks as causal.
This is one of the first studies to describe long-term outcomes of COVID-19 that included a well-defined control group with similar follow-up.
This review was posted on: 7 May 2021