A Case-Crossover Phenome-wide association study (PheWAS) for understanding Post-COVID-19 diagnosis patterns.

BACKGROUND: Post COVID-19 condition (PCC) is known to affect a large proportion of COVID-19 survivors. Robust study design and methods are needed to understand post-COVID-19 diagnosis patterns in all survivors, not just those clinically diagnosed with PCC. METHODS: We applied a case-crossover Phenome-Wide Association Study (PheWAS) in a retrospective cohort of COVID-19 survivors, comparing the occurrences of 1,671 diagnosis-based phenotype codes (PheCodes) pre- and post-COVID-19 infection periods in the same individual using a conditional logistic regression. We studied how this pattern varied by COVID-19 severity and vaccination status, and we compared to test negative and test negative but flu positive controls. RESULTS: In 44,198 SARS-CoV-2-positive patients, we foundenrichment in respiratory,circulatory, and mental health disorders post-COVID-19-infection. Top hits included anxiety disorder (p = 2.8e-109, OR = 1.7 [95 % CI: 1.6-1.8]), cardiac dysrhythmias (p = 4.9e-87, OR = 1.7 [95 % CI: 1.6-1.8]), and respiratory failure, insufficiency, arrest (p = 5.2e-75, OR = 2.9 [95 % CI: 2.6-3.3]). In severe patients, we found stronger associations with respiratory and circulatory disorders compared to mild/moderate patients. Fully vaccinated patients had mental health and chronic circulatory diseases rise to the top of the association list, similar to the mild/moderate cohort. Both control groups (test negative, test negative and flu positive) showed a different pattern of hits to SARS-CoV-2 positives. CONCLUSIONS: Patients experience myriad symptoms more than 28 days after SARS-CoV-2 infection, but especially respiratory, circulatory, and mental health disorders. Our case-crossover PheWAS approach controls for within-person confounders that are time-invariant. Comparison to test negatives and test negative but flu positive patients with a similar design helped identify enrichment specific to COVID-19. This design may be applied other emerging diseases with long-lasting effects other than a SARS-CoV-2 infection. Given the potential for bias from observational data, these results should be considered exploratory. As we look into the future, we must be aware of COVID-19 survivors' healthcare needs.

Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review.

BACKGROUND: This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis. METHODS: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection. RESULTS: Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39-.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44-.63) and 0.34 (95% CI, .25-.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37-.65), Europe (0.44; 95% CI, .32-.56), and United States of America (0.31; 95% CI, .21-.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26-.49), 0.25 (95% CI, .15-.38), 0.32 (95% CI, .14-.57), and 0.49 (95% CI, .40-.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17-.30), followed by memory problems (0.14; 95% CI, .10-.19). CONCLUSIONS: This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system.