Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study

Abstract

Background While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients. Methods 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. Findings We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms. Interpretation The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19. Funding COVIM:„NaFoUniMedCovid19“(FKZ: 01KX2021)

Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK

“…Despite these differences and the markedly lower risk of long COVID diagnosis in primary care versus LS, several risk factor associations were consistent between various LS and in EHR. Findings that long COVID was more common with each decade of age from age 20 to age 70, and was 50% higher in women than men, are consistent with reports from most 4,[29][30][31][32][33] but not all previous studies. (34,35) There was an approximate linear increase in risk with age between 18 and 70 years.…”

“…Over the age of 70, we observed a sharp decline in risk in most LS and EHR. This decline in risk for older adults which has been observed in other studies, 4,29,32 may be explained by selective competing risk of mortality, non-response bias, individuals misattributing long COVID to other illnesses, or a combination of these factors.…”

“…Our finding of a greater risk of long COVID related to adverse prior mental health, has been reported elsewhere, 26 but pre-pandemic general health has not previously been highlighted. 29,31,36 These findings were robust in all analyses including inverse probability weighting for risk of COVID-19. The finding of an excess risk of long COVID in association with asthma across cohorts and primary care records resolves previous conflicting and limited findings, 26,29,35 and provides considerable support for focusing on asthma as a high-risk condition, for example by investigating into whether immune processes seen in asthma play a role in the development of long COVID.…”

“…29,31,36 These findings were robust in all analyses including inverse probability weighting for risk of COVID-19. The finding of an excess risk of long COVID in association with asthma across cohorts and primary care records resolves previous conflicting and limited findings, 26,29,35 and provides considerable support for focusing on asthma as a high-risk condition, for example by investigating into whether immune processes seen in asthma play a role in the development of long COVID. In our analysis weighted for risk of COVID-19 onset, high cholesterol measures were associated with a greater risk of long COVID which has not been reported previously, although only two LS contributed data for metaanalyses of this factor and further studies will be required to confirm or refute this finding.…”

“…26,31,35,37 Findings for overweight/obesity were suggestive of an increased risk again resolving previous uncertainty. 29,35,36 The markedly lower reporting of long COVID in primary care compared to LS suggests only a minority of people with long COVID seek care and subsequently receive a code. Diagnostic codes for long COVID have only recently been instituted and uptake by primary care practitioners has not been uniform.…”