Event Rate and Predictors of Post-Acute COVID-19 Sequalae and the Average Time to Diagnosis in General Population

Abstract

Background: Post-COVID-19 sequalae involves a variety of new, returning or ongoing symptoms that people experience more than four weeks after getting COVID-19. The aims of this meta-analysis were to assess the prevalence of Post-Acute COVID-19 sequalae and estimate the average time to its diagnosis; and meta-regress for possible moderators. Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database. Search terms included; long COVID-19 or post-acute COVID-19 syndrome/sequalae. The criteria for inclusion were published clinical articles reporting the long COVID-19, further, the average time to diagnosis of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Eggers tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The trial was PROSPERO registered (CRD42022328509). Results: Prevalence of post-acute COVID-19 sequalae was 42.5% (95% confidence interval (CI) 36 % to 49.3%). The PACS event rates range was 25 % at four months and 66 % at two months and mostly, signs and symptoms of PASC were experienced at three (54.3%, P < 0.0001) to six months (57%, P < 0.0001), further increasing at 12 months (57.9%, P= 0.0148). At an average of two months, however with the highest event rate (66%), it was not significantly associated with PACS diagnosis (P=0.08). On meta-regression, comorbidities collectively contributed to 14% of PACS with a non-significant correlation (Q = 7.05, df = 8, p = 0.5313) (R-squared analog = 0.14). A cardiovascular disorder especially hypertension as a stand-alone, showed an event rate of 32% and significantly associated with PACS, 0.322 (95% CI 0.166, 0.532) (P < 0.001). Chronic obstructive pulmonary disorder (COPD) and abnormal basal metabolic index (BMI) had higher event rates of PACS (59.8 % and 55.9 %) respectively, with a non-significant correlation (P > 0.05). With a significant association, hospital re-admission contributed to 17% (Q = 8.70, df = 1, p = 0.0032) (R-squared analog= 0.17) and the study design 26% (Q = 14.32, df = 3, p = 0.0025) (R-squared analog= 0.26). All the covariates explained at least some of the variance in effect size on PACS at 53% (Q = 38.81, df = 19, p = 0.0047) (R-squared analog = 0.53). Conclusion: The prevalence of PACS in general population was 42.5%, of which cardiovascular disorders were highly linked with it with COPD and abnormal BMI also being possible conditions found in patients with PACS. Hospital re-admission predicted highly, an experience of PACS as well as prospective study design. Clinical and methodological characteristics in a specific study contributed to over 50% of PACS events. The PACS event rates ranged between 25 % at four months and 66 % at two months with most signs and symptoms experienced between three to six months increasing at 12 months.