What are the risk factors for long-COVID-19 disease/post-COVID syndrome (PCS)?

06 Oct 2021
Respiratory conditions
  • COVID-19
Type of resource
IPCRG COVID-19 and respiratory Q&A

What the research says:

The identification of risk factors for long-COVID/PCS is challenging. Further data and longer-term follow-up are needed to better define those risk factors that offer the best predictive value for ongoing symptoms and whether different risk factors apply to different patient populations. Long-COVID/PCS is not limited to patients with severe acute illness and may emerge following even a mild COVID-19 illness.

Female sex, increasing age and a higher number of symptoms during the acute illness appear to be predictive risk factors for long-COVID/post-COVID syndrome (PCS). Increased levels of D-dimer or C-reactive protein or reduced lymphocyte count during acute illness may also be predictive risk factors (Yong 2021).

Other factors that may contribute to the emergence of long-COVID/PCS but require further research to confirm their predictive value include:

  • Pre-existing comorbidity
  • Prior psychiatric disorder
  • Increased levels of IL-6, procalcitonin, troponin-1, blood urea nitrogen, or neutrophil count during acute illness 

BMI, body mass index; ICU, intensive care unit; PCR, polymerase chain reaction; PCS, post-COVID syndrome.

While prolonged organ-related symptoms can be expected following severe COVID-19, research is ongoing to determine whether any risk factors can be related to specific post-COVID symptoms for those with mild or moderate acute illness. One study has suggested that female sex and a diagnosis of anxiety and depression or antidepressant use may be a risk factor for persistent fatigue (Yong et al 2021).

What this means for your clinical practice:

  • Continue to follow-up with patients once they recover from acute COVID-19 illness of any severity, with particular vigilance for symptoms persisting beyond 12 weeks from onset of the acute illness
  • Maintain particular vigilance for PCS among older, female patients and those with multiple symptoms during the acute phase of the illness

Useful links and supporting references:

Jones R, et al. Risk predictors and symptoms features of long COVID within a broad primary care patient population including both tested and untested patients. Pragmat Obs Res 2021;12:93-104. Available at: https://www.dovepress.com/risk-predictors-and-symptom-features-of-long-covid-within-a-broad-prim-peer-reviewed-fulltext-article-POR. Accessed August 2021.

Moreno-Perez O, et al. Post-acute COVID-19 syndrome. Incidence and risk factors : A Mediterranean cohort study. J Infect 2021;82:373-8. Available at: https://www.journalofinfection.com/article/S0163-4453(21)00009-8/fulltext. Accessed August 2021.

Osmanov IM, et al. Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study. Eur Respir J 2021;2101341. Available at: https://erj.ersjournals.com/content/early/2021/06/10/13993003.01341-2021. Accessed August 2021.

Peghin M, et al. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients. Clin Microbiol Infect. Available at: https://www.sciencedirect.com/science/article/pii/S1198743X21002810. Accessed August 2021.

Sudre CH, et al. Attributes and predictors of long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App. Pre-print, available at: https://doi.org/10.1101/2020.10.19.20214494. Accessed August 2021.

Thompson EJ, et al. Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK. Pre-print, available at: https://doi.org/10.1101/2021.06.24.21259277. Accessed August 2021.

Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis 2021. Available at: https://doi.org/10.1080/23744235.2021.1924397. Accessed August 2021


Dr Fiona Mosgrove (GP and Clinical Lead Grampian Respiratory Improvement Programme, Aberdeen, Scotland, UK) for and on behalf of the IPCRG practice driven answers review group.