A comprehensive analysis revealed how COVID-19 pandemic interventions may have altered the global circulation patterns of seasonal influenza viruses, with test positivity rates dropping by more than 95% during the acute phase of the pandemic (April 2020 to March 2021) compared with prepandemic levels.

In the study, published in Science, investigators from Fudan University and the University of Oxford analyzed molecular, epidemiologic, and international travel data across 12 geographic regions: Africa, North America, South America, Europe, Russia, northern China, southern China, Japan/Korea, South Asia, West Asia, Southeast Asia, and Oceania.

The study utilized a phylodynamic framework combining epidemiologic, genetic, and international travel data, analyzing approximately 2,500 sequences for each influenza subtype or lineage. The methodology employed BEAST v1.10 with BEAGLE library v4 for phylogenetic inference and included an HKY nucleotide substitution model.

Dwell times for H3N2 prior to the pandemic were generally less than 6 months, except for Africa in late 2019. During 2018 to 2019, just one clade (Y3) of B/Yamagata lineage remained in circulation.

Key findings showed that during the acute pandemic phase, influenza test positivity rates decreased by 99.2% for H1N1pdm09, 99.2% for H3N2, 96.9% for B/Victoria, and approximately 100% for B/Yamagata compared with prepandemic averages.

Air passenger traffic remained the principal predictor of global influenza dissemination throughout all study periods, with positive log effect sizes of 0.82 for H1N1pdm09 (95% highest posterior density [HPD] = 0.71–0.94), 0.78 for H3N2 (95% HPD = 0.67–0.90), and 1.06 for B/Victoria (95% HPD = 0.95–1.20).

The investigators divided their analysis into three distinct periods:

• Prepandemic period (January 2017 to March 2020)
• Pandemic period (April 2020 to April 2023): acute phase (April 2020 to March 2021), transition phase (April 2021 to April 2023)
• Postpandemic period (May 2023 to March 2024).

South Asia emerged as a primary trunk location for H1N1pdm09 and H3N2 during acute and transition phases, whereas West Asia maintained B/Victoria circulation. Higher net exports of H3N2 from West Asia were observed during the postpandemic period.

Genetic analysis revealed that B/Yamagata showed a low nonsynonymous to synonymous substitution rate ratio (dN/dS = 0.11, 95% confidence interval [CI] = 0.10–0.12), while B/Victoria exhibited a slightly higher ratio (0.15, 95% CI = 0.14–0.16) with five amino acid residues under positive selection.

The investigators found that while specimen processing for influenza testing remained stable during the acute phase, it doubled during the transition phase. The proportion of laboratory-confirmed influenza cases sequenced during the acute pandemic phase exceeded 10%, later decreasing to prepandemic levels.

An H3N2 epidemic occurred during the 2021 to 2022 Northern Hemisphere winter with a double peak, followed by outbreaks of H1N1pdm09, H3N2, and B/Victoria during the 2022 to 2023 Northern Hemisphere winter.

The investigators noted that their findings demonstrated how seasonal influenza viruses were maintained during and reestablished after pandemic-related behavioral changes, suggesting the need for continued monitoring through coordinated genomic surveillance and evaluation of global transmission patterns.

Conflict of interest disclosures can be found in the study.