Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort

Introduction

Much of the public health response to COVID-19 has been focused on the acute phase of infection, from curtailing transmission to preventing and treating severe disease. However, research suggests that post-acute sequelae after SARS-CoV-2 infection, or long-COVID, can occur in anywhere from 10 to 55%^1–3 and has the potential to overwhelm health systems and economies. While data consistently suggest that long-COVID disproportionately affects those hospitalized at the time of their infection, it is increasingly recognized that persistent symptoms affect those with mild/moderate infections. Moreover, long-COVID also affects all ages, sexes, and races and occurs among individuals without pre-existing comorbidity.^4–6 Symptoms reported by individuals with long-COVID are heterogeneous and affect multiple organ systems.^7,8

While reports have characterized the breadth of symptoms that persist or newly occur in long-COVID, there have been fewer assessments on downstream impacts such as disability. In one study of critically ill hospitalized COVID-19 patients, 48% had decreased functional status and 10% reported severe limitations in their daily life six months post-infection⁹. Similarly, in a Norwegian cohort of hospitalized older patients, 35% reported impaired ability to perform daily activities, 33% reduced mobility, and 43% a decrease in cognitive function six months after hospitalization.¹⁰ While there have been fewer assessments from community-based settings, one study of 328 participants reported that 4.9% had symptoms post-infection that constrained daily activities¹¹. This functional restriction can directly affect employment, caregiving, and independent living.

We characterize physical disability and mental fatigue in those with and without COVID-19 in a large sample of community dwelling adults living in the US from the Johns Hopkins COVID Long Study.

METHODS

RESULTS

Among 7,926 individuals with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity (Table 1). Pre-existing comorbidities were heterogeneous with participants reporting hypertension (15%), diabetes (4.0%), and asthma/other chronic pulmonary conditions (17%). Based on calculated body mass index, 36% were classified as obese. Comparable characteristics of persons with resolved-COVID and no-COVID are included in Table 1.

Initial infection spanned from January 2020-June 2022, with the majority (77%) occurring before January 2021 and vaccine availability. At initial COVID-19 illness, 89% of those with long-COVID and 73% of those with resolved-COVID had not been vaccinated. However, at enrollment, 58% of those with long-COVID and 67% of those with resolved-COVID had completed at least one (adenovirus) or two (mRNA) vaccine doses. The five most reported acute infection symptoms for those with long-COVID were lack of energy (86%), headache (71%), muscle aches (61%), fever (54%), and shortness of breath/dyspnea (52%). While the types of symptoms were comparable for those with resolved-COVID, only 2.4% with resolved-COVID required hospitalization compared to 13% with long-COVID (Table 1).

Prior to COVID-19, 77% of long-COVID participants reported that their general health status was ‘very good’ or ‘excellent’, yet only 6.6% of individuals in this group reported the same health status as before infection, compared to 81% of those with resolved-COVID (Figure 1A). Most individuals reported being physically active before infection (71% of long-COVID, 66% of resolved-COVID). However, 50% of individuals with long-COVID experienced declines in their physical activity, including 33% moving from ‘active’ to ‘sedentary’ compared to 3% among those with resolved-COVID (Figure 1B).

Discussion

In this large and heterogeneous sample from across the US, nearly two-thirds of persons with long-COVID classified as having some disability, a burden that was nearly 11 times that of those with resolved-COVID. Moreover, we identified that 1% were critically physically disabled or unable to function and 5% had critically severe mental fatigue. This has the potential to translate to millions of new disabilities in adults in the US. Considering that 30–90 million people are expected to have long-COVID (10–30% of cases), we might expect 300,000–900,000 people (1% of long-COVID) to be physically incapacitated, and 900,000–2.7 million (3% of long-COVID) to have critically severe mental fatigue. While it is reassuring that those with critically severe disabilities appear to be seeking necessary medical care (reflected by high levels of new physician diagnoses), these disabilities will likely compromise the ability of many to work or care for themselves and others, extending the long-term societal and economic impacts of COVID-19.

Our data was consistent with prior reports suggesting that hospitalization during acute illness is the strongest driver of COVID-19-associated disability. However, we also demonstrate that 60% of non-hospitalized individuals experience at least one long-COVID associated disability and 5.5% were classified with at least one critical disability. Although we observed some associations with age, gender, race, and pre-existing comorbidities with long-COVID disabilities, they contrasted with the risk factors of male gender, age, and comorbidities that have been consistently associated with COVID-19 severity and hospitalization. Essentially, these data suggest that factors predictive of hospitalization or severity of initial infection cannot be used to predict who will develop long-COVID-associated disability among those not requiring hospitalization.

While there was substantial heterogeneity in the presenting symptoms of acute COVID-19 in those with long-COVID, there were some patterns that emerged among those with incident disabilities. Among non-hospitalized individuals, dizziness, tremors, heavy limbs, and dyspnea were consistently associated with increased occurrence and sometimes severity of disability. Even among those hospitalized, dizziness and heavy limbs were related to all types of disability and severity. Dizziness and tremors are neurologic outcomes that may represent multiple disease paths including disruption of the vestibular system and dysautonomia, and postural orthostatic tachycardia syndrome (POTS). Associations of dizziness and tremors with imbalance may also explain observed associations with mobility/IADL disability.^20,21 The sensation of heavy limbs is often attributable to venous insufficiency or peripheral arterial disease. This incident symptom may represent the effect of SARS-CoV-2 on the cardiovascular system with alterations to microvascular perfusion on the peripheral limbs, thromboembolism, and endothelial injury. While the high burden of physician diagnoses particularly among the most severely disabled group suggests that many are seeking clinical care, our data reinforces the need for those with early lingering symptoms to seek medical care that considers careful neurologic, vestibular, cardiovascular, and/or pulmonary evaluations. Additionally, there may be opportunities for the early administration of medications like corticosteroids²¹ or consideration of anti-platelet regimens and physical therapy, although it remains unclear whether early intervention will alleviate long-term impacts.

Additional clarity is needed on whether vaccination reduces disability risk associated with long-COVID. We observed over a 50% reduction in odds for all three disabilities among those with 3+ mRNA/two adenoviral doses and a more modest reduction in odds for those with two mRNA/one adenoviral dose. Some of this effect may be mediated through protection from severe COVID-19 resulting in hospitalization leading to disability. The strong reduction of mobility disability persisted in the two or more mRNA doses/one or more adenoviral dose IV analysis that is robust to measured or unmeasured confounding (Supplement Methods). With increasing viral positivity in the US, the window of complete vaccination (initial doses + booster) prior to infection is closing. However, these data support that vaccines may afford some protection from disabilities, as well as the intended purpose of attenuation of severe infection and hospitalization.

The cross-sectional design prevented us from exploring the impact of vaccination after infection on the resolution and/or exacerbation of COVID-19 associated disabilities. Comprehensive longitudinal studies are needed to explore the association of timing and dose of vaccination as well as number and timing of repeat infections on COVID-19 disability and changes over time. In our sample, we observed a high burden of all disabilities among those with long-COVID. While our sample may be skewed towards individuals reporting long-COVID, it was beneficial to identify common patterns in the long-COVID group, and especially those with disability. We included those with resolved-COVID and no-COVID for comparisons, acknowledging that the pandemic, outside of infection, was stressful and for some traumatic, and may contribute independently to disability. We also lack representation in demographic groups that were especially impacted by the pandemic, and thus we may underestimate the true burden of long-COVID disability across race/ethnicity, socio-economic, and community factors; however, this was minimized in the vaccine analysis by weighting the study sample to the COVID-19 Symptom Survey sample weights which increases the ability to generalize these results to the US population. Nevertheless, representativeness of these analyses depends on the differences in distribution of effect modifiers in our sample as compared to the general population (Supplement Methods and Figures S6.1–S6.3). The use of a study questionnaire provided us the opportunity to capture the heterogeneity in initial and continued symptoms but is subject to recall bias especially when the time of infection was far from enrollment in the study. However, this approach allowed us to be more inclusive of the spectrum of COVID-19 and long-COVID symptoms than studies that use electronic health records that rely on information from those seeking medical care only.

In conclusion, we observed a high burden of physical and mental disability among individuals who are experiencing long-COVID, which may have long term consequences for not only these individuals but society-at-large. Long-term follow-up will be required to understand how and for whom these disabilities will resolve or worsen over time. In the meantime, specialized care is needed for the growing population of persons with long-COVID to reduce the burden and impact of disability.

Supplementary Material