The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves.

Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines. Here, we investigated immune responses to 2 vaccines in patients with CKD to identify predictors of immunological responsiveness.

Animal models of viral respiratory disease often use weight loss as a marker of disease severity; however, this may relate to dehydration and malnutrition that would be corrected clinically. We tested whether parenteral fluid therapy improved weight loss from influenza infection. BALB/c and C57BL/6 mice were infected with A/X31 (H3N2) influenza and randomized to intraperitoneal fluid therapy. Blood glucose was also measured post-viral infection on day 3 and 6 in BALB/c mice and on day 6 in C57BL/6 mice. Parenteral fluids did not alter weight loss or the immunological response to infection, and glucose levels were not abnormal.

Coronavirus disease 2019 (COVID-19) adversely affects patients who are older, multimorbid, and from Black, Asian or minority ethnicities (BAME). We assessed whether being from BAME is independently associated with mortality in end-stage kidney disease (ESKD) patients with COVID-19.