The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study

Front Public Health. 2023 Dec 14:11:1303183. doi: 10.3389/fpubh.2023.1303183. eCollection 2023.


Background: Long COVID is a clinical entity characterized by persistent health problems or development of new diseases, without an alternative diagnosis, following SARS-CoV-2 infection that affects a significant proportion of individuals globally. It can manifest with a wide range of symptoms due to dysfunction of multiple organ systems including but not limited to cardiovascular, hematologic, neurological, gastrointestinal, and renal organs, revealed by observational studies. However, a causal association between the genetic predisposition to COVID-19 and many post-infective abnormalities in long COVID remain unclear.

Methods: Here we employed Mendelian randomization (MR), a robust genetic epidemiological approach, to investigate the potential causal associations between genetic predisposition to COVID-19 and long COVID symptoms, namely pulmonary (pneumonia and airway infections including bronchitis, emphysema, asthma, and rhinitis), neurological (headache, depression, and Parkinson's disease), cardiac (heart failure and chest pain) diseases, and chronic fatigue. Using two-sample MR, we leveraged genetic data from a large COVID-19 genome-wide association study and various disorder-specific datasets.

Results: This analysis revealed that a genetic predisposition to COVID-19 was significantly causally linked to an increased risk of developing pneumonia, airway infections, headache, and heart failure. It also showed a strong positive correlation with chronic fatigue, a frequently observed symptom in long COVID patients. However, our findings on Parkinson's disease, depression, and chest pain were inconclusive.

Conclusion: Overall, these findings provide valuable insights into the genetic underpinnings of long COVID and its diverse range of symptoms. Understanding these causal associations may aid in better management and treatment of long COVID patients, thereby alleviating the substantial burden it poses on global health and socioeconomic systems.

Keywords: COVID-induced cardiac disease; COVID-induced fatigue; COVID-induced neurological disorders; Mendelian randomization; long COVID.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / epidemiology
  • Chest Pain
  • Fatigue Syndrome, Chronic*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Headache
  • Heart Failure*
  • Humans
  • Mendelian Randomization Analysis
  • Parkinson Disease*
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2 / genetics

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by Yenepoya (Deemed to be University) Seed Grant to HU (YU/Seed Grant/110-2022).