Discrepant serological findings in SARS-CoV-2 PCR-negative hospitalized patients with fever and acute respiratory symptoms during the pandemic.

Coronavirus Disease 2019 (COVID-19) serology has an evolving role in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, its use in hospitalized patients with acute respiratory symptoms remains unclear. Hospitalized patients with acute respiratory illness admitted to an isolation ward were recruited. All patients had negative nasopharyngeal swab polymerase chain reaction (PCR) for SARS-CoV-2. Serological studies using four separate assays (cPass: surrogate neutralizing enzyme-linked immunosorbent assay [ELISA]; Elecsys: N-antigen based chemiluminescent assay; SFB: S protein flow-based; epitope peptide-based ELISA) were performed on stored plasma collected from patients during the initial hospital stay, and a convalescent visit 4-12 weeks later. Of the 51 patients studied (aged 54, interquartile range 21-84; 62.7% male), no patients tested positive on the Elecsys or cPass assays. Out of 51 patients, 5 had antibodies detected on B-cell Epitope Assay and 3/51 had antibodies detected on SFB assay. These 8 patients with positive serological test to COVID-19 were more likely to have a high-risk occupation (p = 0.039), bacterial infection (p = 0.028), and neutrophilia (p = 0.013) during their initial hospital admission. Discrepant COVID-19 serological findings were observed among those with recent hospital admissions and bacterial infections. The positive serological findings within our cohort raise important questions about the interpretation of sero-epidemiology during the current pandemic.

Combined use of live-attenuated and inactivated influenza vaccines to enhance heterosubtypic protection.

The limited protection of current commerical vaccines necessitates the investigation of novel vaccine strategies for unpredictable outbreaks. To investigate the feasibility of using vaccines derived from Group 1 influenza A virus to induce broadly cross-reactive immune responses against multiple influenza subtypes, we tested a panel of sequential 4-dose immunization regimens in mice. Mice were treated with inactivated (seasonal H1N1, pandemic H1N1 and H5N1) and vaccinia virus-based H5N1 live-attenuated vaccines in different combinations. Mice were then challenged by viruses of either Group 1 (H1N1) or Group 2 (H3N2, H7N7) influenza virus. All studied sequential 4-dose vaccinations could induce some degrees of heterosubtypic protection in mice. Amongst all these regimens, the combined use of inactivated and live-attenuated vaccines could achieve the best heterologous protection. These results highlight the synergistic effect of combining different vaccine platforms to enhance heterosubtypic protection against influenza viruses.