Virological surveillance of influenza viruses in the WHO European Region in 2019/20 – impact of the COVID-19 pandemic

The COVID-19 pandemic negatively impacted the 2019/20 WHO European Region influenza surveillance. Compared with previous 4-year averages, antigenic and genetic characterisations decreased by 17% (3,140 vs 2,601) and 24% (4,474 vs 3,403). Of subtyped influenza A viruses, 56% (26,477/47,357) were A(H1)pdm09, 44% (20,880/47,357) A(H3). Of characterised B viruses, 98% (4,585/4,679) were B/Victoria. Considerable numbers of viruses antigenically differed from northern hemisphere vaccine components. In 2020/21, maintaining influenza virological surveillance, while supporting SARS-CoV-2 surveillance is crucial.

The ending of the 2019/20 influenza season in the World Health Organization (WHO) European Region coincided with the start of the first wave of the coronavirus disease  pandemic. This study assesses potential impacts of the pandemic on influenza surveillance and presents characteristics of influenza viruses detected in the Region in 2019/20, relative to contemporary components of influenza vaccines for the northern hemisphere (NH).

Influenza virological surveillance in Europe, influenza season 2019/20
In the WHO European Region, the 2019/20 influenza season started in week 47 2019, peaked for 2 weeks, weeks 05 and 06 2020, and returned to baseline levels (< 10% positivity in sentinel samples) very rapidly in week 13 2020, following widespread public health and social measures implemented to control COVID-19 ( Figure 1). Influenza type A viruses (120,493; 72.9%) dominated over type B (44,774; 27.1%). Of 47,357 subtyped influenza A viruses, 26,477 (56%) were A(H1) pdm09 and 20,880 (44%) were A(H3) viruses. The lineage of 4,679 B viruses was determined and 4,585 (98%) were B/Victoria lineage viruses [1,2]. National Influenza Centres (NICs) in the Region collect influenza virological surveillance data, conduct genetic and antigenic characterisation of viruses and report to The European Surveillance System (TESSy) on a weekly basis. The WHO Collaborating Centres (WHO CC) in London and in Atlanta (at the Centers for Disease Control and Prevention (CDC)) provide NICs with post-infection ferret antisera or other antisera raised against egg and/or cell culture-propagated vaccine/reference viruses for antigenic characterisation or typing/subtyping using haemagglutination inhibition (HAI) assays. WHO CC London also provides a list of reference sequences for the assignment of viruses to haemagglutinin (HA) gene clades/subclades following Sanger or next generation sequencing (NGS) [3]. NICs share representative influenza-positive samples with the WHO CC for in depth antigenic and genetic analyses essential for decision-making at vaccine composition meetings (VCMs).
Fifty Member States of the WHO European Region reported 165,267 influenza virus detections between week 40 2019 through week 20 2020. Relative proportions of circulating influenza A(H3), A(H1)pdm09 and B/Victoria lineage viruses varied between countries [1,4]. Only 24 of the 50 countries reporting influenza detection data contributed virus characterisation data.
Of all viruses detected, 2% (2,601/165,267) were antigenically and 2% (3,403/165,267) were genetically characterised ahead of the 2020 southern hemisphere (SH) VCM [1]. Virus characterisation data were used to determine the similarity of circulating viruses to the components of influenza vaccines for the 2019/20 NH influenza season and to assess implications of the COVID-19 pandemic on influenza surveillance and its output.

Influenza virus characterisation in the WHO European Region in light of the COVID-19 pandemic
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in March 2020, relatively late in the course of the influenza season in the Region, and the total number of influenza virus detections was comparable to previous seasons. However, the COVID-19 pandemic adversely affected the generation and reporting of virus characterisation data.

Genetic and antigenic analysis of circulating influenza viruses, 2019/20
For specimens collected from week 40 2019 to 20 2020, genetic characterisation data of 3,403 viruses were reported to TESSy by 21 countries and antigenic characterisation data of 2,601 viruses by 13 countries. Table  1 and Table 2 provide the full list of numbers of viruses in each antigenic group and genetic clade, reporting category by week of sample collection.
Among A(H1)pdm09 viruses, of the 1,246 that were genetically characterised, 1,121 (90%) belonged to the 6B.1A5A group, moreover, of the 1,032 antigenically characterised, the majority (n = 859; 83%) were similar to the A/Brisbane/02/2018 vaccine virus. However, 173 A(H1)pdm09 viruses were not attributed to any predefined antigenic category, indicative of possible antigenic drift; of these viruses, genetic information was reported for only 48, nine of which had the HA1 N156K

Ethical statement
An ethical approval was not needed for this study, as data are not identifiable back to the patients from whom they originated.

Discussion
Based on the data, influenza activity in the European Region appears to have ended abruptly in week 13 2020, earlier than previous seasons [1,8,9]. Responses to the COVID-19 pandemic, e.g. changes in access to and utilisation of healthcare and SARS-CoV-2 nonpharmaceutical control measures, such as school closures and social distancing, likely impeded continued surveillance and spread of influenza. This resulted in few influenza viruses being detected after week 13 2020 and, overall, fewer viruses being characterised, despite the obvious efforts from the laboratories under high pressure and overwhelming work load. Redirection of laboratory testing capacities to SARS-CoV-2, with shortages of laboratory supplies and human resources,

Table 1b
Antigenic characteristics of influenza viruses as reported to TESSy by week of sampling, WHO European Region, week 40 2019-week 20 2020 (n = 2,601 viruses characterised in 13 countries)      [10]. The issue of poor recognition of circulating A(H3) viruses by immune responses to egg-propagated vaccine virus remained [11].
Data from the 2020 SH influenza season show that circulation of influenza viruses was extremely limited in the SH winter and also elsewhere for the NH interseasonal period [5,9,12]. Similar low levels of influenza might be expected in the WHO European Region in the 2020/21 season, if COVID-19-related public health measures are implemented. However, co-circulation of both influenza and SARS-CoV-2 viruses is possible, and should warrant resource-related and operational prioritisation efforts to ensure that continued evidencebased decisions can be made at WHO influenza VCMs. In either scenario, NICs will be challenged to ensure collection of representative specimens for influenza virus detection and subsequent virus characterisations with laboratory capacities being divided between influenza and SARS-CoV-2 surveillance [13]. The European Centre for Disease Prevention and Control (ECDC) and WHO Regional Office for Europe have issued joint interim guidance on what approaches should be used to maintain influenza surveillance during the winter period with the ongoing COVID-19 pandemic [13].
In terms of way forward, NICs play crucial roles in surveillance of seasonal influenza and zoonotic events and are responsible for arranging the essential shipments of representative specimens to the WHO CC to ensure there are sufficient data for making VCM recommendations. With increasing number of avian influenza outbreaks and continued evolution of influenza viruses in swine, there is also need for maintained vigilance in public health laboratories to ensure detection of zoonotic events for pandemic preparedness purposes [14,15]. In the 2020/21 season, efforts are needed to ensure maintenance of influenza surveillance, but also to support COVID-19 surveillance to understand SARS-CoV-2 transmission and inform national responses to the pandemic. Switzerland: We would like to thank the medical practitioners of the swiss sentinel network for their contribution in providing nasopharyngal specimens.