Causal associations of COVID-19 with health and disease outcomes: a systematic review and meta-analysis

ObjectivesThe COVID-19 pandemic has posed a substantial threat to global health. Despite numerous clinical observations and causality investigations, understanding of the diseases progression and recovery process following infection remains limited. This systematic review and meta-analysis evaluates the causal connections between COVID-19 and various diseases using Mendelian randomization studies to provide robust theoretical underpinnings for the development of effective rehabilitation and intervention strategies. MethodsWe systematically searched PubMed, Embase, Web of Science, and Scopus for studies on Mendelian randomization related to COVID-19 published up to October 21, 2024. We used an extensive search strategy with the keywords "Mendelian randomization" and "COVID-19". Two pairs of coauthors independently extracted data on study characteristics, exposure, and outcomes, resolving discrepancies through discussion. We included studies that considered susceptibility to COVID-19, hospitalization, or severe infection as the exposure and disease-related effects or impacts on human health as outcomes. We assessed the quality of the included studies using the MR-STROBE criteria and extracted the relative risk (odds ratio [OR]) using a random-effects model for meta-analysis. This study is registered with PROSPERO, CRD42025615426. ResultsOf the 1654 studies identified, 87 met the inclusion criteria for our meta-analysis. The primary outcome suggests that COVID-19 is associated with an increased risk of cardio-cerebral vascular diseases. Subgroup analyses identified an increased risk of neuropsychiatric disorders, including optic nerve disorders, epilepsy, schizophrenia, generalized anxiety disorder, stroke, myocardial infarction with COVID-19. There is also a notable association between COVID-19 and the immune system, particularly neuromyelitis optica spectrum disorders and myasthenia gravis. ConclusionsThis study demonstrates that COVID-19 infection has direct causal effects on human health or certain diseases at the genetic level, which may manifest as increased or decreased susceptibility to disease and changes in disease severity.