To describe pre-COVID-19 pandemic current practices in virological investigations, including type, frequency of samplings, and documented viruses, in sudden unexpected death in infancy (SUDI) and to compare results according to the cause of death.

Between May 2015 and December 2019, infants under 2 years of age included in the French SUDI registry were classified in one of 4 groups by causes of death according to the classification by Goldstein et al. : unexplained (SIDS), infectious, explained but noninfectious, and undetermined. Sampling sites and viruses detected were described, and then SIDS and explained deaths (control group) were compared.

Among 639 infants, 3.6% died of an established viral infection. From 23 sampling sites and 2238 samples, 19 virus species were detected. Overall, 43.3% of infants carried a virus, with no significant difference between SIDS infants and the control group ( P = .06). We found wide variations in frequencies of samples by site (550 for nasopharynx to one for saliva). The highest positivity rate was from the nasopharynx (195/2238; 8.7%). Rhinovirus was the predominant virus detected (135/504; 26.8%), mostly in SIDS (83/254; 32.7%). We found no significant difference between positivity rates and distribution of viruses between the SIDS and control groups. At-autopsy virological analysis never contributed to determining the cause of death.

Current practices in virological investigations in SUDI are heterogeneous, with wide variability despite published guidelines. Investigations should be limited to the most relevant sites, and systematic at-autopsy sampling should be reconsidered. We found no association between virus detection and SIDS.