Influenza season 2021/2022
The 2021/22 influenza season
Once more, Denmark experienced an unusual influenza season in 2021/22. The season was short and intense, and it started later than usual. Influenza was largely absent until early February, but then picked up speed, and the start of the season therefore coincided with the end of the restrictions imposed to prevent COVID-19. The 2021/22 season brought the highest number of confirmed cases ever seen in a single week, but the weekly number of tested persons were also twice as high as previous seasons. Despite the high testing activity, the percent positive remained high, at 20-30%, when number of cases peaked.
Even so, the influenza season was generally mild with only a limited number of hospitalised patients and few influenza-related deaths. In conclusion, we avoided the double epidemic of influenza and COVID-19, which was causing concern ahead of the season.
As was the case in the 2020/21 season, we achieved a high vaccination coverage in the group of elderly people aged 65 years and above, as approx. 78% accepted the offer of free vaccination. In contrast to previous years, influenza vaccination was also offered to children aged 2-6 years; but in this group, the vaccination coverage only reached approx. 29%.
The Sentinel Surveillance System was extended in 2021/22 in order to include COVID-19 surveillance, increase the number of samples taken and initiate year-round monitoring of respiratory infections. In future, this will allow us to detect and monitor atypical outbreaks of respiratory infections occurring beyond the typical influenza season.
Influenza in humans and animals is monitored by various surveillance systems. More information is provided about each of the systems in the box shown at the end of this annual report.
Occurrence of influenza-like illness (ILI) in the 2021/22 season
In the season from week 39 2021 through week 23 2022, an average of 112 physicians submitted electronic reports detailing the number of ILI patients they have attended in general practice.
The proportion of patients who contacted their general practitioner with ILI is presented in Figure 1, and Figure 2 shows ILI activity compared with the previous five seasons. As from autumn and until the end of the year, the ILI proportion remained at a low to moderate level compared with expectations, the share then declined to a very low level in the first nine weeks of 2022, when the share normally follows an inclining trend. However, as from week 9, an increase was observed in the proportion of ILI patients seen in general practice, and the remaining monitoring systems also recorded steep increases. This trend peaked in week 15 after which the curve declined rapidly to a low level. It should be noted that ILI activity in general practice also reflects the occurrence of other airway infections that cause ILI, including COVID-19, which may explain the increase observed in the autumn of 2021.
Emergency service physicians' monitoring
Despite the high number of people who were infected with influenza in this season, the consultation percentage recorded by the emergency call service physicians remained low, below 1%, throughout the season. The highest share was seen in the period with a high level of influenza infection, but even in this period the consultation percentage remained at a lower level than recorded in previous seasons (barring the 2020/21 season), Figure 3.
Among the season’s approx. 10,000 Influmeter participants, approx. 5,500 persons reported their symptoms weekly from October 2021 to May 2022. The Influmeter season has been characterised by a very low share (1.1-3.4%) with influenza-like symptoms compared with the previous seven seasons (0.8-8.1%). In the 2021/22 season, only a slight increase was observed of approx. 3.4%, in February in weeks 6-8, Figure 4.
Laboratory diagnostics in the MiBa/dashboard
Data extractions from the MiBa show that a total of 188,582 persons were tested for influenza from week 40 2021 to week 20 2022. Among these, 16,220 tested positive to influenza. The overwhelming majority tested positive for influenza A (16,144 cases), whereas only 76 cases were caused by influenza B, Figure 5. In this season, far more Danes were tested than in previous seasons, and far more weekly tests were performed than in previous seasons. Despite the large number of tests, almost no cases of influenza were recorded in the autumn and early winter of 2021.
Not until February 2022 did the number of confirmed cases rise; and in week 12, the epidemic peaked at 3,391 confirmed cases before largely being over in week 20. Figure 6 shows the number of confirmed cases per week recorded in the 2021/22 season and in the previous five seasons. Here it is clear that more cases were found in a single week than in any single week in the previous seasons. Furthermore, the epidemic curve was steep and appeared later than is usually the case, and the 2021/22 season start coincided with the lifting of the last restrictions imposed to prevent COVID-19 on 1 February 2022.
Furthermore, the percent positive was high and comparable to those observed in previous seasons when the epidemic peaked. In week 12, when the epidemic peaked, the percent positive was 27%.
This is remarkable considering that far more tests were made when the epidemic peaked than was the case during previous epidemics.
Furthermore, in the 2021/22 season, a larger share of the confirmed cases was seen in children aged 7-14 years than is usually the case. This trend was also observed in the 2019/20 season and may therefore reflect a higher level of transmission among children but also increased testing activity among children.
Hospital admissions and intensive care
From week 40 in 2021 through week 20 in 2022, a total of 3,836 patients with laboratory-confirmed influenza were admitted to hospital, Table 1. A total of 3,819 had influenza A (99.6%), 17 had influenza B (0.4%). The median age for persons admitted to hospital was 69 years. Slightly more than half of the patients admitted to hospital (55%) were registered as having received influenza vaccination at least 14 days before their positive test; and among those admitted to hospital aged 65 years or more, 77% had been vaccinated at least 14 days before their positive test.
A total of 236 deaths were recorded among persons admitted to hospital with influenza, defined as death within 30 days after testing positive. This is considerably fewer deaths than in a normal influenza season.
Table 2 presents the distribution of risk factors among patients admitted to hospital with influenza. As shown, 84% of all admitted persons had an increased risk of running a serious influenza disease course.
Among those admitted to hospital, 232 patients received intensive care within during admission.
In the 2021/22 season, a total of 261 deaths were recorded in relation to influenza among the 16,220 patients affected by influenza (1.6%).
Laboratory surveillance at Statens Serum Institut (SSI)
In the course of the season, the National Danish WHO Influenza Centre at the SSI received a total of 5,295 influenza samples for testing and characterisation of influenza virus, including 2,641 samples submitted by the sentinel physicians, 167 diagnostic samples submitted by GPs and other laboratories, and 2,487 positive surveillance samples diagnosed and submitted by the departments of clinical microbiology.
The submitted positive influenza samples are subtyped if possible. A total of 97% of the samples submitted were typed in the course of the season. Among the typed samples, nearly all were influenza A virus. In the influenza A virus group, the H3N2 subtype comprised 99% and H1N1pdm09 1%. Only three influenza B virus cases were typed; all belonged to the Victoria line. The entire season was dominated by the H3N2 subtype, Figure 7.
Sequencing and virus characterisation of 699 randomly selected monitoring samples showed that 98.1% were Influenza A H3N2 of the genetic subgroup 3C.2a1b.2a.2. The genetic subgroup A(H3N2) 3C.2a1b.1a comprised 0.1%, the genetic subgroup A(H1N1) 6B.1A.5a.1 comprised 1.4% and the genetic subgroup A(H1N1) 6B.1A.5a.2 comprised 0.3%,
Results from the extended sentinel surveillance in the present season
The extended sentinel surveillance was introduced in this season. Samples are analysed continuously at the SSI, and the results are returned to the general practitioners. The SSI performed PCR-based testing of 2,641 airway samples for more than 20 known respiratory viruses. Among these, 1,673 samples tested positive for one or more respiratory viruses, including 711 (42.5%) for influenza. Among other respiratory viruses, rhinovirus (19.0%) was the most frequently observed virus group and SARS-CoV-2 (17.8%) the second most frequent, followed by common coronavirus (14.4%), human metapneumovirus (13.0%) parainfluenza virus (11.4%), enterovirus (8.5%) and adenovirus (8.8%). In 10% of the positive samples, more than one respiratory virus was detected.
Figure 9 presents the development in detected respiratory viruses from week to week for all of Denmark throughout the season. Worth noting is the high occurrence of metapneumovirus in late 2021, the late start of the influenza season in February 2022 after which the season continued until May, and the current high occurrence of rhinovirus and parainfluenza virus. Among the parainfluenza-positive samples, 75% were parainfluenza virus of type 3.
Monitoring of antiviral resistance
The National Influenza Centre for the WHO at the SSI carries the national responsibility for testing influenza samples from patients who initiate antiviral treatment for antiviral resistance. In this season, no samples were received from patients receiving antiviral treatment in this season. In contrast, a total of 696 sequenced monitoring samples were tested for resistance to the neuroaminidase inhibitors oseltamivir (Tamiflu®) and zanamivir (Relenza®). Mutations that cause resistance to Tamiflu® and Relenza® were found in a sample from one patient. The presently circulating influenza viruses are all naturally resistant to the ion channel inhibitors amantadine and rimantadine.
As previously, seasonal influenza vaccination was offered free of charge to persons with an increased risk of running a serious influenza course in the period from 1 October 2021 through 15 January 2022 and to pregnant women in their second and third trimesters and persons with immune deficiency and their contacts until 1 March 2022. Furthermore, as in season 2020/21, vaccination was offered to healthcare and nursing staff and, as a novelty, also to children aged 2-6 years in the form of a nasal vaccine containing live attenuated influenza virus.
The Danish Health Authority’s objective for vaccination coverage was 95% for all target groups, barring children for whom the objective was 85%.
A total of 1,707,584 persons were vaccinated in the season, as calculated at the end of the season on 25 May 2022. The elderly age groups, in particular, have received the vaccination offer well, as persons aged 65 years or more have recorded a vaccination coverage exceeding 75%, which is the objective of the World Health Organization (WHO). Among nursing home residents, the coverage reached approx. 82%.
The coverage of the remaining target groups was somewhat lower, 25-35%, Table 3. Furthermore, for some risk groups, considerable geographical differences were recorded in coverage, which may be due to underlying socio-demographical differences.
Influenza vaccine effectiveness
The effectiveness (VE) of this year’s influenza vaccines varied by age group. Children aged 2-6 years were offered the live attenuated influenza vaccine, and in this group, the VE was rather high at 62% (95% confidence interval: 52-69%) among patients whose parents contacted their GP, and 56% (95% confidence interval: 28-73%) among children admitted to hospital. In the 7-44-year age group, VE was somewhat lower at 19% (95% confidence interval: 10-28%) among patients contacting their GP and 22% (95% confidence interval: 2-37%) among patients admitted to hospital. In the 45+-year age group, the influenza vaccine had no effect.
The late start of influenza occurrence meant that more than 3-4 months passed from the influenza vaccine was given until the influenza season started, which is a problem because the effect of the influenza vaccines wane over time. This waning immunity is particularly pronounced for the oldest age groups. It is therefore unsurprising that the highest effect was observed among children as children are generally very capable of forming antibodies following vaccination. Additionally, the vaccinated children received two doses of a live attenuated vaccine, which may also have affected the VE. For comparison, Sweden reported a relatively high VE among the oldest age groups, but in Sweden the influenza season occurred very early, around November 2021, in contrast to the unusually late season observed in Denmark.
Recommendations for the composition of the influenza vaccines for the 2022/23 season
The WHO recommends that 4-valent influenza vaccines for the next influenza season in 2022/23 comprise the following virus components:
- A/Victoria/2570/2019 (H1N1)pdm09-like virus
- A/Darwin/9/2021 (H3N2)-like virus• B/Austria/1359417/2021 (B/Victoria lineage)-like virus
- B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
The Danish Health Ministry’s executive order with guidelines on the use of the influenza vaccines for the 2022/23 season have yet to be published but will be presented in a future issue of EPI-NEWS once published.
Transmission of influenza infection from animals to humans
Before 2021, swine influenza had not been detected in humans in Denmark, but sporadic cases have occasionally been reported from other countries. In January 2021, the SSI detected Enkeltstaende tilfalde af ny influenza virus-variant hos en borger in a person, and in November 2021 a second case was detected. The cases were unrelated and were detected at a time when common seasonal influenza virus was not circulating. Virus from both of the two patients was of the type influenza A, subtype H1N1, in variants only seen in pigs. The two viruses were, however, genetically different, which means that different viruses were found in the two affected patients. The cases were thoroughly investigated and no signs were found of further transmission to other people. Therefore, the cases were considered sporadic cases.
Influenza in pigs
In 2021, the monitoring of influenza virus in pigs was based on samples from a total of 857 submissions from 647 different farms, which had been sent for diagnostic testing at Danish veterinary laboratories. Typically, 3-5 samples were included in each submission. The submissions were made from all parts of Denmark, and influenza virus was detected in all periods of the year, even though the summer semester recorded fewer submissions and a lower share of positive submissions. A total of 53% of the submissions, corresponding to 377 submissions, tested positive for influenza A virus. All positive samples were tested to determine if they were of the H1pdm subtype, and subtyping of the proteins hemagglutinin (HA) and neuraminidase (NA) was completed for 312 submissions. The most common subtypes detected in Danish pigs were H1avN2sw, H1pdm09N1av and H1N1pdm09. For more information, please see the monitoring page of DK-VET.
Influenza in birds and mammals
The 2021/22 season recorded outbreaks with clade 22.214.171.124b H5 highly pathogenic avian influenza (HPAI) virus in Europe, with extraordinarily many findings in both wild birds and poultry. In Denmark, 11 outbreaks were recorded in poultry flocks following clinical suspicion of HPAI. In the same period, HPAI virus was detected in more than 100 wild birds that were found dead; primarily geese, swans, buzzards and seagulls. Furthermore, HPAI virus was detected in a limited number of cases in apparently healthy wild ducks during the autumn of 2021. The viruses detected in the poultry flocks are the same as those detected in wild birds. Therefore, the virus was probably introduced into the poultry flocks via direct or indirect contact to wild birds. Read more at the website of the Danish Veterinary and Food Administration.
So far, HPAI virus has only rarely been detected in mammals; however, a common seal, which was found dead on a beach on the island of Funen in the autumn of 2021, tested positive to HPAI virus. That was the first time ever that HPAI virus was detected in a mammal in Denmark. However, in other European countries, this season has brought a number of similar sporadic cases including detection of HPAI virus in seals, foxes and other wild predators.
Avian influenza virus has never been detected in humans in Denmark, but cases have been observed in Asia, in particular, where they have triggered small outbreaks.
Influenza monitoring methodsHere, we describe influenza monitoring methods in place for monitoring of influenza in humans and animals. For more detailed information about monitoring methods, please see the SSI website (monitoring among humans) and the website of DK-VET (monitoring among animals).
SentinelThe sentinel surveillance system is based on reports from general practitioners and is a voluntary, sample-based reporting system. The general practitioners submit weekly reports of the number of consultations in their practice and the number of patients with influenza-like illness (ILI). The submitted data are used to calculate the ILI consultation percentage. Additionally, the physicians typically take two weekly samples from patients with ILI. The samples are used to detect and characterise the circulating airway viruses.
Emergency service physicians' monitoringThe ILI occurrence was also monitored weekly via the national monitoring efforts of the emergency service physicians and via the emergency phone service 1813 of the Capital Region of Denmark.
InflumeterInflumeter is a voluntary web-based monitoring system by which citizens may report influenza-like symptoms. Monitoring is active in the influenza season from week 40 to week 20 the following year.
Laboratory testsThe National Influenza Centre for the WHO at the SSI performs extended diagnostics, including subtyping and testing for any changes in the influenza virus on part of the positive influenza samples submitted. Furthermore, the laboratory handles diagnostics of the samples submitted through the sentinel surveillance system where samples are tested for a wide range of airway viruses, including influenza and SARS-CoV-2.
Dashboard and the weekly reportsAs a novelty, this year the SSI has developed an interactive dashboard for monitoring of laboratory-confirmed influenza and influenza vaccination coverage. The dashboard is updated on all working days during the influenza season, making it possible to follow how influenza develops more closely than was previously the case. The dashboard supplements the weekly reports provided on the website. Patients who have had influenza detected are identified in the Danish Microbiology Database (MiBa), information on hospital admissions is collected from the National Patient Registry and information about deaths is collected from the CPR Registry.
Vaccination coverageThe coverage of the influenza vaccination programme is monitored by target groups. Some target groups are defined by age, whereas other target groups are identified according to register data. Nursing home residents are reported based on the nursing home list, healthcare workers are identified based on the occupational registry (DREAM) and persons below 65 years of age with underlying medical conditions are recorded based on data from the National Patient Registry. Vaccination coverage data are collected from the Danish Vaccination Registry (DVR).
Influenza surveillance in pigsUnder the auspices of DK VET, which is a consortium counting Statens Serum Institut and the University of Copenhagen, a systematic, prospective and passive monitoring effort is made annually to monitor circulating influenza viruses in Danish pigs based on samples from pigs with clinical signs of influenza. The overall objective is to monitor which influenza virus types and genotypes are in circulation among Danish pigs and to map causes of disease in the population of pigs to underpin the strategic objective of limiting the use of antibiotics in Danish pig farms. The results are used to elucidate a range of veterinary and zoonotic aspects.
Influenza surveillance in birdsDK-VET is a national reference laboratory for avian influenza and handles laboratory tests relating to influenza in wild birds and poultry, both on suspicion of avian influenza and as a general monitoring system. Passive monitoring is in place of avian influenza in wild birds that have been found dead. This work is handled by the Danish Veterinary and Food Administration. The objective is to ensure that we receive early warning of any highly pathogenic avian influenza in Denmark. If dead waterfowls, birds of prey and crow birds are found, this may be reported by citizens to the Danish Veterinary and Food Administration who handles any sampling needed. The corresponding laboratory tests are completed by DK-VET. The national active monitoring for avian influenza virus in healthy wild birds is handled by DK-VET in collaboration with the Danish Veterinary and Food Administration and the National History Museum of Denmark. The objective is to characterise viruses from wild birds and study their epidemiology.
This annual report is also described in EPI-NEWS no. 27/2022.