Asian Journal of Research in Infectious Diseases

Influenza is caused by influenza viruses, which infect host respiratory epithelial cells by binding the viral envelope hemagglutinin to sialic acid receptors on the cell surface. Hemagglutinin can induce red blood cell agglutination in vitro, a hallmark of viral infectivity. Our previous studies demonstrated that the 35 kDa low-molecular-weight hyaluronan (HA35) can also induce agglutination of human and multiple animal erythrocytes in vitro, suggesting that HA35 may interfere with the binding between viral hemagglutinin and host cells. This retrospective case series analyzed the incidence of influenza over nine years among three volunteers who had long-term exposure to HA35 without influenza vaccination. In addition, one case of severe influenza occurring in a high-altitude region was evaluated for clinical improvement following short-term, high-dose HA35 administration. Together, these observations were used to assess the potential anti-influenza effect of HA35. During a nine-year follow-up period, none of the three volunteers who received long-term HA35 injections and oral supplementation developed influenza. During the COVID-19 pandemic, all three participants were infected with the coronavirus and developed typical symptoms, suggesting that HA35 had no preventive effect against non-hemagglutinin-dependent viruses. In the high-altitude case, the patient’s fever and systemic symptoms markedly improved following short-term high-dose oral HA35 treatment, with no severe complications observed. These observations suggest that HA35 may have potential preventive and therapeutic effects against influenza. Although limited by the small sample size, this case series provides preliminary clinical evidence supporting further investigation of HA35 nasal formulations and devices in influenza prevention and control.