Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map

Juan Victor Ariel Franco, Luis Ignacio Garegnani, Gisela Viviana Oltra, Maria-Inti Metzendorf, Leonel Fabrizio Trivisonno, Nadia Sgarbossa, Denise Ducks, Katharina Heldt, Rebekka Mumm, Benjamin Barnes, Christa Scheidt-Nave, Juan Victor Ariel Franco, Luis Ignacio Garegnani, Gisela Viviana Oltra, Maria-Inti Metzendorf, Leonel Fabrizio Trivisonno, Nadia Sgarbossa, Denise Ducks, Katharina Heldt, Rebekka Mumm, Benjamin Barnes, Christa Scheidt-Nave

Abstract

Post-COVID-19 conditions, also known as 'Long-COVID-19', describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.

Keywords: COVID-19; evidence map; long-COVID-19.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA Flow diagram.
Figure 2
Figure 2
Distribution of studies per country (darker blue indicates a higher density of studies). Footnotes: Darker blue indicates a higher density of studies per country. The top 10 countries with the highest number of studies included the United States (87), Italy (75), the United Kingdom (50), China (47), Spain (42), Germany (24), France (18), India (16), Turkey (13), and Brazil (12).
Figure 3
Figure 3
Screenshot (fragment) of an evidence map sorted out by study design, outcomes, and subgroup of adults (red) or children (blue).

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