Long-Term Symptoms Associated with SARS-CoV-2 Infection among Blood Donors

ImportanceLong-term symptoms, lasting more than 4 consecutive weeks after acute COVID-19 disease, are an important consequence of SARS-CoV-2 infection. Many prior studies have lacked a non–SARS-CoV-2–infected control population to distinguish background prevalence of symptoms from the direct impact of COVID-19 disease.ObjectiveTo examine the prevalence of long-term physical and mental health symptoms associated with SARS-CoV-2 infection in a large population of blood donors based on self-report and serologic test results.Design, Setting, and ParticipantsThis cross-sectional study included American Red Cross blood donors (aged ≥18 years) who were surveyed between February 22 and April 21, 2022, about new long-term symptoms arising after March 2020 and their SARS-CoV-2 infection status. All participants underwent at least 1 serologic test for antinucleocapsid antibodies between June 15, 2020, and December 31, 2021.ExposuresSARS-CoV-2 infection as defined by a self-reported, confirmed acute infection or antinucleocapsid antibody positivity.Main Outcomes and MeasuresNew long-term symptoms since March 2020, including 5 symptom categories (neurologic, gastrointestinal, respiratory and cardiac, mental health, and other).ResultsAmong 818 361 individuals who received the survey, 272 965 (33.4%) responded, with 238 828 meeting the inclusion criteria (138 576 [58.0%] female; median [IQR] age, 59.0 [47.0-67.0] years). Of the 83 015 individuals with a history of SARS-CoV-2 infection, 43.3% reported new long-term symptoms compared with 22.1% of those without a history of SARS-CoV-2 infection. After controlling for age, sex, race and ethnicity, and number of underlying conditions, those with a history of SARS-CoV-2 infection had an increased odds of new long-term symptoms compared with those without (adjusted odds ratio [AOR], 2.55; 95% CI, 2.51-2.61). Female sex and a history of chronic conditions were associated with new long-term symptoms. Long-term symptoms in the other category (AOR, 4.14; 95% CI, 4.03-4.25), which included changes in taste or smell, and the respiratory and cardiac symptom categories (AOR, 3.21; 95% CI, 3.12-3.31) were most associated with prior SARS-CoV-2 infection. Mental health long-term symptoms were also associated with prior SARS-CoV-2 infection (AOR, 1.05; 95%, CI, 1.02-1.08).Conclusions and RelevanceThis study’s findings suggest that long-term symptoms lasting more than 4 weeks are common in the adult population, but there is a significantly higher prevalence among those with SARS-CoV-2 infection. Continued efforts to define and track long-term sequelae of SARS-CoV-2 using a control group without infection and serologic information to include those who had asymptomatic or unidentified infections are needed.