Post-Acute Sequelae of COVID-19

Post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, encompass a broad spectrum of symptoms and organ-system impairments that persist or arise beyond the acute phase of SARS-CoV-2 infection. Manifestations range from chronic fatigue, respiratory dysfunction and cardiovascular abnormalities to neurocognitive deficits and psychiatric disturbances. Pathophysiological mechanisms are multifactorial, involving persistent inflammation, endothelial injury, immune dysregulation and viral persistence in some tissues. The clinical trajectory is heterogeneous; symptoms may wax and wane, with relapses triggered by exertion or stress. Although severity of the initial illness influences risk, even mild cases can develop disabling sequelae. The global burden of PASC is substantial, with implications for health-care systems and rehabilitation services. Early recognition, multidisciplinary assessment and personalised management strategies are essential to mitigate long-term disability and optimise recovery.

Research from Nature Portfolio

Recent immune-profiling studies have revealed distinct myeloid and lymphoid signatures in individuals with persistent symptoms, including heightened antibody responses to SARS-CoV-2 and other herpesviruses, coupled with altered soluble mediators such as reduced cortisol. These findings may inform biomarker development and therapeutic targeting. A two-year follow-up of a large veteran cohort demonstrated that while many sequelae decline over time, a significant cumulative burden of disability-adjusted life years persists, particularly among those hospitalised. This underscores the need for long-term surveillance and resource allocation. In non-hospitalised adults, a primary care database analysis identified over sixty symptoms significantly associated with SARS-CoV-2 infection after twelve weeks, with risk factors including female sex, socioeconomic deprivation, comorbidities and younger age, highlighting the demographic and clinical determinants of chronic disease courses.

Post-Acute Sequelae of COVID-19 publication trend

The graph below shows the total number of articles in post-acute sequelae of covid-19 across all publications each year (not limited to Nature Index journals).

Technical terms

Post-acute sequelae of COVID-19 (PASC): Persistent or new symptoms lasting beyond four weeks after acute SARS-CoV-2 infection.

Post-exertional malaise: A marked exacerbation of symptoms following physical or mental activity.

Humoral immunity: The component of the immune response mediated by circulating antibodies.

RNAemia: The presence of viral RNA in the bloodstream, indicating systemic dissemination.

Disability-adjusted life year (DALY): A composite measure of overall disease burden, combining years of life lost and years lived with disability.

References

1. The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID. Signal Transduction and Targeted Therapy (2023).
2. Distinguishing features of long COVID identified through immune profiling. Nature (2023).
3. Postacute sequelae of COVID-19 at 2 years. Nature Medicine (2023).
4. Symptoms and risk factors for long COVID in non-hospitalized adults. Nature Medicine (2022).
5. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell (2022).
6. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Scientific Reports (2021).