Risk Factors Associated With Post-COVID-19 Condition: A Systematic Review and Meta-analysis

Abstract

Importance: Post-COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective: To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources: Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study selection: The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data extraction and synthesis: Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main outcomes and measures: The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results: The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and relevance: This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial registration: PROSPERO Identifier: CRD42022381002.

Figure 1.. Association of Sex With Post−COVID-19 Condition (PCC), 2021 to 2022

Female sex was shown to have a statistically significant association with high risk of developing PCC. The dotted line represents the point where there is no difference between the 2 groups; the dashed line represents the average effect of all studies when pooled together. Note that when >1 study by the same author(s) was identified, only 1 was included in the meta-analysis (in the relevant subgroup meta-analysis). Data for 10 longitudinal studies^,,,,,,,, of patients 18-96 years old were obtained solely from a single study by Thompson et al, including ALSPAC G0, which refers to the Avon Longitudinal Study of Parents and Children-Generation 0; GS, the Generation Scotland−the Scottish Family Health Study; MCS, Millennium Cohort Study; NS, Next Steps (formerly the Longitudinal Study of Young People in England); BCS70, the British Cohort Study 1970; NCDS, the National Child Development Study; TwinsUK, the UK Adult Twin Registry; and USOC, Understanding Society−the UK Household Longitudinal Survey. OR indicates odds ratio.

Figure 2.. Association of Age With Post−COVID-19 Condition (PCC), 2021 to 2022

Older individuals (40-69 and ≥70 y) had a significantly higher risk of ongoing persistent PCC symptoms compared with adults <40 years old. The dotted line represents the point of no difference between the 2 groups, and the dashed line represents the average effect of all studies when pooled together. Data for 10 longitudinal studies^,,,,,,,, of patients 18-96 years old were obtained solely from a single study by Thompson et al, including GS, which refers to the Generation Scotland−the Scottish Family Health Study; TwinsUK, the UK adult Twin Registry; and USOC, the Understanding Society−the UK Household Longitudinal Survey. OR indicates odds ratio.

Figure 3.. Association of Smoking Status With Post−COVID-19 Condition (PCC), 2021 to 2022

Individuals who smoked had 1.10 times higher risk of developing PCC compared with individuals who did not smoke. The dotted line represents the point of no difference between the 2 groups, and the dashed line represents the average effect of all studies when pooled together. Data for 10 longitudinal studies^,,,,,,,, of patients 18-96 years old were obtained solely from a single study by Thompson et al, including ALSPAC G0, which refers to the Avon Longitudinal Study of Parents and Children-Generation 0; ALSPAC G1, the Avon Longitudinal Study of Parents and Children-Generation 1; BCS70, British Cohort Study 1970; GS, Generation Scotland−the Scottish Family Health Study; MCS, the Millennium Cohort Study; NS, Next Steps (formerly the Longitudinal Study of Young People in England); NCDS, the National Child Development Study; and USOC, Understanding Society−the UK Household Longitudinal Survey. OR indicates odds ratio.

Figure 4.. Association of Vaccination Status With Post−COVID-19 Condition (PCC), 2021 to 2022

Individuals who were vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC than individuals who had not been vaccinated. The dotted line represents the point of no difference between the 2 groups, and the dashed line represents the average effect of all studies when pooled together. OR indicates odds ratio.