Abstract
BACKGROUND: Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction (AMI) and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke. METHODS: We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. Studies capturing respiratory viral infection(s) using laboratory-confirmatory methods, incidence of AMI or stroke (ischaemic or haemorrhagic), and those involving human participants in any country, will be assessed for eligibility. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, study population, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997.