Background and objectives: This randomized controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in critically ill influenza patients requiring invasive mechanical ventilation. Methods: Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomized to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for ten days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after five days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores. Results: Viral clearance rates after five days of treatment were low and similar between the double (15%) and triple-dose groups (10%). No significant differences were observed in 28-day mortality, hospital mortality, ICU or hospital length of stay, or duration of mechanical ventilation between the double and triple-dose groups. However, patients receiving triple doses exhibited a faster decline in influenza A viral load. Conclusions: Triple doses of oseltamivir did not significantly improve virological or clinical outcomes compared to double doses in severe influenza.

Background The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses. Methods Pre- and post-vaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV. Results Among SARS-CoV-2 infection naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The pre-vaccination antibody response to the common cold human coronaviruses did not negatively impact the post-vaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralisation tests. Conclusions Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV.