In a recent study posted to the medRxiv* preprint server, researchers investigated the potential drivers of a global decline in influenza virus circulation during the coronavirus disease 2019 (COVID-19) pandemic.

Background

Since 2020, with the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the studies showed an apparent shortening of the flu season in tropical and some northern hemisphere countries. The trend continued in 2021 and expanded to countries in the southern hemisphere like Australia and New Zealand in the following 18 months.

Since both influenza virus and SARS-CoV-2 have a similar transmission route, social restriction measures imposed during the pandemic and non-pharmaceutical interventions (NPIs) against COVID-19 also hindered influenza circulation globally. Studies have investigated this phenomenon for specific countries but not globally. A global analysis of the observed decline in influenza circulation during the COVID-19 pandemic could help assess future viral circulation and interpret the current transmission trends.

About the study

In the present study, researchers used data from the FluNet influenza database to compute influenza change for 166 countries and all 13 weeks-long trimesters between March 2020 and September 2021 relative to a pre-pandemic period between 2014 and 2019. There were 20 trimesters between winter 2014 to 2015 and autumn 2019 (pre-pandemic period) and six trimesters between spring 2020 to summer 2021 (pandemic period).

Next, the researchers computed the percentage of influenza-positive cases for six pandemic trimesters. Additionally, they determined the ratio between the percentage of influenza-positive cases during pandemic trimesters and the mean percentage of positive cases in the corresponding pre-pandemic trimesters.

The team used random forests (RFs)-based VSURF algorithm to identify influenza decline predictors of a significant value from a list of 20 covariates (e.g., COVID-19 incidence, COVID-19 pandemic response, COVID-19 pandemic preparedness, demography, weather) from public sources and the International Air Transport Association (IATA). Finally, they retained covariates with minimum variables, having a prediction error less than the minimum prediction error plus one standard deviation (SD). As per the predictors of influenza decline, the team classified similar observations in time and space using a regression tree. Last, they performed a robustness analysis to check for stochastic fluctuations in the dataset analyzed using the regression tree and the criteria for including the FluNet records.

Study findings

The FluNet data showed higher peaks in seasonal influenza cases in northern countries and lower peaks for southern countries during the pre-pandemic period. The authors observed a sharp drop in the percentage of influenza-positive tests during the COVID-19 pandemic period to a minimum of 0.04% during July and August 2020.

The authors made 376 trimester-country observations from 112 countries during the pandemic. Compared to two orders of magnitude during the pre-pandemic period, the percentage of influenza positive tests varied over five orders of magnitude across countries and trimesters during the pandemic period. Contrary to the expectations, the percentage of positive influenza tests was more than 100 times smaller for 135/376 trimester-country observations. Notably, Japan reported zero positive tests out of 26114 processed tests in spring 2021. Conversely, the percentage of positive tests was 15% in Haiti during Winter 2020-21 compared to barely 2.2% before the pandemic.

During spring 2020, the decline in influenza circulation was less than 90% from the pre-pandemic period for 46/65 countries. In the following trimesters, this decline became more pronounced for Europe, Mexico, North America, and Japan during the winter 2020-21 and spring 2021. Likewise, the decline became pronounced for several Southern-hemisphere countries during summer 2020 and summer 2021.

The regression tree analyzed data from 93 countries and 330 trimesters. While North America and Europe had a low influenza decline despite strict restrictions during the COVID-19 pandemic in the spring of 2020, tropical countries showed a lesser decrease in influenza cases despite poor pandemic preparedness. In the tropical countries, the COVID-19 case incidence and the strength of COVID-19 response were also lower compared to the European and American nations.

After spring 2022, countries of temperate regions grouped to show a steep decline in influenza circulation. These nations had high COVID-19 incidence and stringent social restrictions and were highly prepared for a pandemic. The analysis also identified four countries with 'no COVID-19’ cases, with a low influenza decline overall. Intriguingly, these countries had not imposed strict social restrictions but only strict border controls to maintain the lowest reduction levels.

Conclusions

The study showed a decline in influenza circulation globally, and of the 11 predictors of the log relative influenza level, identified COVID-19 daily cases and infectious disease vulnerability index (IDVI) as the two key covariates responsible for this decline, following Breiman’s rule. More importantly, the study analysis pointed at a heterogeneous spatiotemporal decline in influenza circulation during the COVID-19 pandemic.

Further, the authors observed a non-linear association between the observed decline in influenza circulation and the sociodemographic stage of the COVID-19 pandemic covariates. Similar to its decline, a resurgence of influenza circulation could also take a diverse path. A reseeding of influenza could drive seasonal epidemics in several countries and increase cases in the susceptible populations, especially children.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.