Viral infection and sudden non-cardiac death: A systematic review

Sudden non-cardiac death (SNCD) is a clinical entity comprising deaths lacking previous clinically significant symptoms, and in which the mechanisms of death do not involve the heart. Infection is a major cause of SNCD, particularly in children, and viruses are frequently involved in the disease process. Nevertheless, SNCD of viral infectious causes remains poorly characterized. Thus, a systematic review of the literature describing the association between viral infection and the development of SNCD was performed.

PRISMA statement guidelines were followed in this systematic review. A literature search was conducted across MEDLINE, Scopus and Web of Science databases. Studies considered eligible were autopsy series or cohort studies of sudden death cases, in which evidence of viral disease as a cause of death was demonstrated, along with identification of causative agents.

Twelve studies published between 1996 and 2020 were included in this review. Selected studies were categorized into three groups according to the study population: infants and young children (up to four years of age); presumed sudden infant death syndrome patients; and older individuals (five years of age and older). SNCD with viral implication represents a minority of sudden death cases in all age groups, with infants and young children having a higher prevalence across studies. Respiratory infection was the main cause of viral SNCD, with influenza virus and respiratory syncytial virus being the most commonly identified agents in older individuals, and infants and young children respectively. Disseminated infection, gastrointestinal infection, and meningitis were other identified causes of SNCD in children.

No studies have directly assessed the frequency and causes of viral SNCD. Infants and young children show a considerable, but variable, prevalence of this clinical entity. Wider implementation of post-mortem virological molecular testing may help uncover previously unknown cases. More research into viral SNCD is needed, especially in the adult population.