Genotyping may contribute to a smarter response to adenovirus infections

Incorporating genotyping of human adenovirus (HAdV) infections in clinical practice may inform risk stratification and treatment decisions, according to a new Singapore study.

“For Singapore and other countries considering new HAdV treatment and control measures, we strongly recommend periodic but routine HAdV genotype surveillance with a goal of collecting the HAdV prevalence data necessary to make informed decisions,” said researchers.

In the 533 HAdV-positive clinical samples included in the analysis, the B3 genotype was the most prevalent (35.6 percent), followed by B7 (15.4 percent), E4 (15.2 percent), C2 (11.8 percent) and C1 (4.9 percent) genotypes. [J Infect Dis 2020;221:566-577]

Of the participants, 300 were included in the retrospective cohort, whose information came primarily from clinical records. In this group, which was predominantly paediatric (n=245; 55 adults), HAdV-B7 was the most common genotype.

The remaining 233 patients were available for prospective analysis. The most prevalent genotype in this cohort was HAdV-B3 (26.2 percent), followed by HAdV-E4 (25.8 percent) and HAdV-B7 (18.5 percent). Twenty-two patients were immunocompromised and were found to be significantly more likely to have severe disease (adjusted odds ratio [OR], 11.4, 95 percent confidence interval [CI], 3.8–34.8).

Being infected with HAdV-C2 (adjusted OR, 8.5, 95 percent CI, 1.5–48.0), HAdV-B7 (adjusted OR, 3.7, 95 percent CI, 1.2–10.9), HAdV-E4 (adjusted OR, 3.2, 95 percent CI, 1.1–8.9) or an unknown genotype (adjusted OR, 5.7, 95 percent CI, 2.0–16.2) were also significant risk factors for severe disease.

Stratified analyses showed that in the 396 paediatric patients, HAdV-B3 was the most prevalent genotype, detected in almost half of this group (47.0 percent). This was followed distantly by HAdV-C2 (14.6 percent) and HAdV-E4 (13.1 percent).

In children, being infected with HAdV-C2 (adjusted OR, 23.1, 95 percent CI, 3.1–173.3) or an unknown (adjusted OR, 9.8, 95 percent CI, 1.7–56.3) genotype, as well as being below 1 year of age (adjusted OR, 17.9, 95 percent CI, 1.3–240) significantly predicted severe disease.

On the other hand, HAdV-B7 was found in 28.5 percent of the 137 adult participants and emerged as the most prevalent genotype. This was followed by the HAdV-E4 (21.2 percent) and HAdV-C2 (3.6 percent).

“This is the first large-scale study to systematically describe clinical HAdV genotypes in Singapore. Our results highlight the prevalence of HAdV-B3 and an increase in morbidity due to HAdV-E4 and HAdV-B7 paediatric infections in Singapore,” said researchers. “Importantly, patients with HAdV-C2, HAdV-E4 and HAdV-B7 were more likely to have severe disease.”

“Hence, it seems prudent for public health officials and clinicians to consider using antiviral therapies and HAdV vaccines in Singapore,” they added.

In the present study, participants were enrolled from the Singapore General Hospital and the KK Women’s and Children’s Hospital. Viral DNA were extracted and subjected to polymerase chain reaction for genotyping.

“Our study could have been strengthened by testing blood from all study patients, or by testing matched patient controls to demonstrate a stronger probability of disease association,” the researcher said, noting that mixed HAdV infections could not be ruled out and is reflected in the high proportion of untypable samples, particularly in adults. Future studies should take these issues in consideration when designing methodologies.