In this prospective cohort of individuals with COVID-19 infection, 30% of patients developed a subset of symptoms associated with PASC. This large, diverse cohort achieved a longitudinal follow-up of 80% of patients after the acute COVID-19 illness. Studying a diverse population treated in a single health system, we are able to control for factors such as access and quality of care often lacking in existing studies.5,12 This health system-based COVID-19 population reveals the startling findings that age, race, and economic disadvantage appear unassociated with development of PASC. This contrasts with COVID-19 infection rates, hospitalizations, and deaths that are disproportionately higher in racial and ethnic minority communities and older people.13,14
Existing prospective studies have not evaluated race and ethnicity and its association with PASC. Sudre et al. found increasing age, female gender, hospitalization, and more than five symptoms in the first week of illness to be associated with PASC, but were unable to analyze the impact of ethnicity due to incomplete data.7 Other studies have described hospitalized patients as more likely to be older, not White, and with lower household incomes compared to outpatients,12 but evaluation of the association between race/ethnicity, SVI, insurance, and PASC were not done.
Current data indicate that ethnic minorities represent a disproportionate number of COVID-19 cases, hospitalizations, and deaths in the USA.13,14,15 Ethnic minorities in the USA diagnosed with COVID-19 were likely to have a greater number of underlying clinical comorbidities,16 lower socioeconomic status,17 loss of health insurance during the pandemic,18,19 and poor access to healthcare. In cohort studies of patients hospitalized for COVID-19, race and ethnicity were not independently associated with in-hospital mortality after adjusting for factors such as age, sex, comorbidities, insurance, and neighborhood deprivation.16,20 This suggests that access to care is an important factor in COVID-19 outcomes. In our study, race and ethnicity was not associated with developing PASC. One possible explanation is that patients had access to the same health system with standardized follow-up. Another possible explanation is that factors that contribute to risks of contracting COVID-19 are not as important in the COVID-19 recovery process and development of PASC. Another factor to consider is whether report of symptoms and expectations for recovery differ across socioeconomic, ethnic, and racial groups and whether the tools used to detect PASC equitably capture these reports.
Existing literature suggests that women were more likely than men to develop PASC,7 whereas our data found a non-statistically significant trend in this direction. It has been suggested this may be due to differences in immunity with a higher prevalence of autoimmune disease in women.21 Diabetes and elevated BMI were associated with developing PASC, which may be due to increased inflammation seen in SARS-CoV-222 potentially leading to microvascular and macrovascular complications.23,24 Interestingly, surviving transplant patients were less likely to develop PASC. The dampened host inflammatory response to COVID-19 for those on immunosuppression agents may play a role, as suggested by a prior study showing solid organ transplant recipients had a faster decline in disease severity over time.25
Surprisingly, patients with commercial insurance had double the likelihood of developing PASC compared to patients with Medicaid. This association will be important to explore further to understand if insurance status in this group is representing unmeasured demographic factors or exposures.
In the acute period of illness, the most commonly reported clinical symptoms among patients who fit our PASC definition were fatigue then shortness of breath, in line with existing studies.1,2 Although fatigue was the most common persistent symptom in hospitalized and non-hospitalized patients, this was followed by loss of sense of smell in outpatients and shortness of breath in inpatients, which is in line with previous studies.3,5 This variation in symptoms at presentation and over time suggests differences in the clinical phenotypes of those with mild to moderate COVID-19 treated in the outpatient setting compared to those with severe COVID-19 requiring hospitalization.
Strengths of our study include a large diverse cohort of COVID-19 patients prospectively followed in a single health system with a large number of organ transplant patients, and standardized longitudinal data to assess symptom evolution over time. Study limitations include potential bias from subjective rating of symptoms and functional status, evaluation of a limited subset of symptoms encapsulated by PASC, not having a comparator group of patients with persistent symptoms after non-COVID hospital admissions, and limited information about pre-existing conditions in our patient population. In addition, survivorship bias may exist where the analysis was limited to individuals that survived to at least 30 days after COVID-19 diagnosis, and referral bias in the outpatient cohort, as only patients deemed clinically high risk were referred to the program, which may affect the generalizability in the outpatient cohort.