Persistent Symptoms and Sequelae after SARS-CoV-2 Infection Not Requiring Hospitalization: Results from Testing Denmark, a Danish Cross-Sectional Survey

Abstract

Background: SARS-CoV-2 infection has been associated with persistent symptoms (long-COVID). We assessed the burden of long-COVID among non-hospitalized PCR-confirmed adults.

Methods: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and COVID-19 associated symptom questions. Non-hospitalized respondents with a positive SARS-CoV-2 PCR-test three or more months before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and BMI. Propensity score weighted odds ratios (OR) and ORs for risk factors were estimated for each health outcome.

Findings: In total, 728 cases and 7280 controls were included. The attributable risk of at least one long-COVID symptom was 25·1 per 100 cases (95% confidence interval (CI): 22·3, 27·6). Compared to controls, cases reported worse general health (OR: 6·0, CI: 5·0, 7·2) and had higher odds for a broad range of symptoms, particularly loss of taste (OR: 12·2, CI: 9·8, 15·2) and smell (OR: 11·7, CI: 9·4, 14·5). Physical and Mental Component Summary scores were also significantly reduced with differences of -2·5 (CI: -3·1, -1·8) and -2·3 (CI: -3·1, -1·6) respectively. Female sex and severity of initial infection were major risk factors for long-COVID symptoms.

Interpretation: Non-hospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and one in four reported persistence of at least one long-COVID symptom.

Funding Information: This study was supported by grants from the Danish Ministry of Health (2012461) and the Tryg Foundation. MvW and LS were supported by the Independent Research Fund Denmark (grant # 8020-00284), and the Carlsberg Foundation, Semper Ardens Research Project (grant # CF20- 0046). The funders did not influence study design, conduct or reporting.

Declaration of Interests: FF, LØ, and TB have received grants from Novo Nordisk Foundation. LS has received grants from Nordforsk and the Carlsberg Foundation. HN and TB have received payments/honoraria for activities related to pharmaceutical industries. TB has received grants from and has served on advisory boards for various pharmaceutical industries. All other authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval Statement: This study was performed as a national surveillance study under the authority task of the Danish national infectious disease control institute Statens Serum Institut (SSI), Copenhagen, Denmark, and in collaboration with a consortium of Danish research institutions. According to Danish law, national surveillance activities from the SSI do not require approval from an ethics committee. In the invitation letter, participants were informed about their rights, including the right to withdraw from the study and have their submitted data deleted. The study was performed in agreement with the Helsinki II declaration and registered with the Danish Data Protection Agency (P-2020-901). Participation was strictly voluntary, no incentives were given, and all data were self-reported. All personal data obtained through the Enalyzer tool were kept in accordance with the general data protection regulation and data protection law stated by the Danish Data Protection Agency.

Note: This paper has been published by Open Forum Infectious Diseases, Volume 10, Issue 1, January 2023, ofac679, https://doi.org/10.1093/ofid/ofac679

Keywords: COVID-19, SARS-CoV-2, long-COVID, post-COVID syndrome, Post-Acute Sequelae of SARS-CoV-2 infection, PASC, point-of-care-test, POCT, cross-sectional survey, quality of life, Health-related quality of life, SF-12, short-form-12, Testing Denmark, Denmark, propensity scores, Odds ratio, matching, risk factors