Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospitalization: a Danish population-based cohort study

research in context

Evidence prior to this study

To identify existing studies on post-acute effects, delayed complications, or long-term effects of mild or asymptomatic SARS-CoV-2 infection, we used PubMed from initiation to September 25, 2020 (ie the date of public registration of the study protocol). We used the following search string: (COVID-19Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study OR SARS-CoV-2Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study) AND (((long term[title/abstract] OR delayed[title/abstract]) AND complications[title/abstract]) OR consequences[title/abstract] OR ((permanent[title/abstract] OR persistence[title/abstract]) AND symptoms[title/abstract])).

After registration of the study protocol, further literature was identified in relevant medical journals and preprint servers up to January 22, 2021 – e.g. medRxiv. We mainly considered observational studies and reviews on post-acute or long-term effects of SARS-CoV-2 infection, but also considered case reports when they reported potentially serious complications. Observational studies of post-acute complications of moderate-to-severe COVID-19—that is, in hospitalized individuals—reported a moderate to high prevalence of severe late complications such as ischemic stroke (1.6–2.5%) and venous thromboembolism (1.5–21 %) and reduced lung function (11-22%). We did not identify any studies that examined severe post-acute complications of mild or asymptomatic SARS-CoV-2 infection. We identified three published studies and one large, as yet unpublished, patient-initiated survey examining symptom persistence after SARS-CoV-2 infection in individuals who do not require hospitalization. Overall, the three published studies report a high prevalence of symptoms such as persistent dyspnea (10-30%) and fatigue (30-40%) up to 6 months after SARS-CoV-2 infection. In the patient-initiated survey, which recruited individuals from “Long COVID” social media support groups, more than 95% experienced fatigue and more than 75% experienced dyspnea. The main limitation for all studies was the lack of a control group of people without COVID-19.

added value of this study

Our population-based cohort study includes all Danish residents who tested positive for SARS-CoV-2 but were not hospitalized for COVID-19 during the first wave of the COVID-19 pandemic (8983 people). For reference, we identified an age, gender, and calendar time-matched reference cohort of 80,894 people who tested negative for SARS-CoV-2 and were not hospitalized. We observed no increased risk (absolute risk difference

Implications of all available evidence

The absolute risk of delayed acute complications after SARS-CoV-2 infection not requiring hospitalization is low, although late venous thromboembolism can occur. SARS-CoV-2 positive individuals are at increased risk of initiating bronchodilator therapy and being hospitalized for shortness of breath 2 weeks to 6 months after primary infection. The increased rate of GP visits and outpatient hospital visits could indicate ongoing symptoms.

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