Genetic and Antigenic Characterization of an Influenza A(H3N2) Outbreak in Cambodia and the Greater Mekong Subregion during the COVID-19 Pandemic, 2020

Abstract

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. Importance The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine.

Global patterns and drivers of influenza decline during the COVID-19 pandemic

“…The largest reduction was in summer 2020, and a progressive increase was seen again till September 2021. Temperate countries had the largest reduction, while it was limited in the tropics [11,14,31,32].…”

“…Understanding how this decline occurred may help interpret the current influenza trends and anticipate future viral circulation. While the issue has been described for specific countries or regions [2][3][4][5]7,8,[11][12][13], little work has been done at the global scale [14,15] [16].…”

Egg-adaptation pathway of human influenza H3N2 virus is contingent on natural evolution

“…The recent emergence of L194P incompatibility suggests that the preference of egg-adaptive pathway has been evolving. To understand the preference of egg-adaptation pathway in recent human H3N2 strains, we analyzed the HA sequences of 72 egg-passaged H3N2 strains 8 from years 2019 to 2021, which belong to antigenically distinct clades [22][23][24]. By comparing the HA sequences between the egg-passaged strains and their non-egg-passaged counterparts, we observed that egg-adaptive mutations often emerged at residues 160, 186, 190, 194, 219 and 225 (Figure 4 and Supplementary Table 4).…”

Peculiar H3N2 outbreak in São Paulo during summer and emergence of the Omicron variant

“…Influenza virus is associated with considerable morbidity and mortality worldwide. These epidemics occur annually and can be prevented through prophylactic vaccination and mitigated with interventions such as social control measures and specific antiviral use ( 1 , 2 ). Since the recognition of the widespread community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), surveillance indicators for influenza have reduced worldwide ( 3 ).The measures implemented for coronavirus disease 2019 (COVID-19), including physical distancing, wearing masks, quarantining, and restricting virus spread/circulation, are also essential to reduce infections caused by influenza and respiratory syncytial viruses; thus, the detection levels of these respiratory viruses became historically low and reduced numbers of influenza viruses were available for WHO characterization than in previous years ( 4 , 5 )…”

“…This outbreak presents some peculiar features. First, it occurred during the Brazilian summer, an atypical situation when it comes to the seasonal flu virus ( 2 ). Flu circulation during summer is usually minimal because weather conditions are less favorable for the transmission of respiratory droplets and aerosols ( 6 ).…”