Integrated surveillance of respiratory infections in 2023/24 - combined report

Integrated surveillance of respiratory infections in 2023/24 - combined report

Statens Serum Institut (SSI) expanded the existing surveillance of respiratory infections in the autumn of 2023. Thus, joint surveillance is now in place of influenza virus, SARS-CoV-2 and respiratory syncytial virus (RSV). In addition to the three major respiratory viruses, joint monitoring in the 2023/24 season also included Bordetella pertussis (whooping cough) and Mycoplasma pneumoniae as these bacterial respiratory infections circulated at an epidemic level in 2023. Thereby, in the autumn of 2023, Denmark experienced simultaneous circulation of the five major respiratory pathogens. Therefore, this annual report on the 2023/24 joint respiratory surveillance describes all five diseases.

Influenza

Influenza is monitored all year round, but the period from week 40 in one year to week 20 in the following year is when influenza virus is known to circulate. When the incidence of influenza begins to increase, the flu season has started.

In week 46, 2023, SSI announced having observed an increasing incidence of influenza and that we expected an early season. Already by week 51, 2023, a total of 1,870 people were diagnosed with influenza virus, the highest weekly number of detected cases in the season. After a short-term decline in the number of detected influenza cases over Christmas and New Year, the number of cases increased again in January 2024, Figure 1.

Season 2023/24 was dominated by influenza A virus with 18,489 confirmed cases, of which 5,285 (29%) were hospitalised, whereas only 373 influenza B virus cases were detected, of which 40 (11%) were hospitalised. The 0-1-year age group had the highest influenza A incidence at 963 cases per 100,000, followed by the 85+ year age group with 588 and the 2-6-year age group with 518 cases per 100,000. Among people who were diagnosed with influenza A virus in the 2023/24 season, 2.2% died within 30 days, which is the same level as in the 2022/23 season.

A subset of the samples tested for influenza virus is sent to Statens Serum Institut. In the 2023/24 season, the SSI received a total of 9,083 respiratory samples, of which 3,361 (37%) tested positive for influenza virus. Influenza A virus was detected in 3,254 samples; influenza B virus, in 107 samples. A total of 3,153 samples were subtyped, of which 2,272 (72%) were influenza A(H1N1)pdm09, 877 (28%) were influenza A(H3N2) and four (0.1%) were B/Victoria. Influenza B/Yamagata has not been seen globally since the spring of 2020. An overview of the subtype distribution observed during the season is presented in Figure 2.

SSI characterises a selection of positive influenza samples annually. These samples are analysed for antiviral resistance, among others. Compared with previous years, an increase in samples with a reduced response to oseltamivir and zanamivir among influenza A(H1N1)pdm09-positive samples was seen in the 2023/24 season.

The distribution of influenza types and subtypes varied between age groups. The season was dominated by influenza A(H1N1)pdm09, which accounted for more than half of all influenza cases in all age groups, but with the highest proportion being recorded in the 0-1-year, 2-6-year and 51-64-year age groups. The highest proportion of influenza A(H3N2) occurred in the 7-15-year, 15-25-year and above-65-year age groups. As in previous seasons, influenza B occurred more frequently in the 7-14-year and 15-25-year age groups than in other age groups. Figure 3 shows the percentage distribution of influenza A(H1N1), A(H3N2) and B within each age group in the 2023/24 season.

COVID-19

Covid-19 is caused by SARS-CoV-2, which is a coronavirus. The occurrence of SARS-CoV-2 is not yet seasonal, as is the case for most other respiratory viruses, but is instead dependent on the introduction of new variants. After several large infection waves during 2022, the number of detected cases and hospitalised patients with COVID-19 were at a low level in the summer of 2023, Figure 4. As of early August 2023, the number of laboratory-confirmed cases followed an increasing trend and peaked in weeks 49 and 50 of 2023 with 2,712 and 2,688 weekly cases, respectively. After that, the SARS-CoV-2 wave of infection declined towards the spring of 2024, when the incidence remained at a very low level. From week 21 in 2023 to week 20 in 2024, a total of 24,939 people were diagnosed with SARS-CoV-2, of whom 10,186 (41%) were hospitalised.

For most of 2023 and until the end of October, the most frequently occurring SARS-CoV-2 variants were dominated by viruses that are recombinants of the Omicron variant, such as XBB.1.16* and EG.5.1* (* means “including subvariants”). From late October 2023 to February 2024, the recombinant BA.2.86* and the subvariant JN.1* were dominant, contributing to a wave of infections observed during that period. The development of these variants has continued, and since March 2024, JN.1* has been dominant, particularly subvariants KP.2 and KP.3, Figure 5.

SARS-CoV-2 is monitored in wastewater throughout the year by two weekly samples from 29 sampling sites distributed across Denmark. In June and July 2023, the concentration of SARS-CoV-2, and thus community transmission, remained at a very low level. From August to the end of October 2023, the SARS-CoV-2 concentration was at a medium level, and from there, a sharp increase to a very high level was observed in December 2023 and January 2024, indicating widespread community transmission. Based on the high concentrations, we assume that half of the population was infected during the winter. During the spring of 2024, the concentration followed a slowly decreasing trend, reaching a low level in May with only a few infected people. The wave recorded in the winter of 2023/24 was caused by the emergence of the JN1 variant and its subvariants.

Respiratory syncytial virus (RSV)

RSV is monitored all year round, but after the COVID-19 pandemic, RSV circulation was observed already from late summer and early autumn. When the incidence of RSV starts to increase, we say that the season has started. In week 43 of 2023, the SSI announced that the incidence of RSV had started rising and that, in line with the previous two years, the expectation was that the season would occur earlier than it did before the COVID-19 pandemic. The 2023/24 season peaked in weeks 50 and 51 with 1,407 and 1,391 weekly cases, respectively, Figure 7. A total of 10,114 cases were detected, of which 3,251 (32%) were hospitalised. The RSV incidence was highest among 0-5-month-old children with 8,371 cases per 100,000 people, followed by 6-11-month and 1-year-old children, with 3,769 and 3,437 cases per 100,000, respectively. Among those diagnosed with RSV in the 2023/24 season, 109 (1%) died within 30 days, the majority of whom were 75 years and older, whereas no deaths were observed among young children.

The RSV season was dominated by the RSV-A subtype (83.5%). RSV-B was found in 15.5% of the samples tested, and 1% had both RSV-A and RSV-B. The two subtypes circulated concurrently, and no time shift between them was observed.

Mycoplasma pneumoniae

From the introduction of the initial COVID-19 restrictions in March 2020 to August 2023, only sporadic Mycoplasma pneumoniae (MP) cases were recorded. From August 2023 onwards, the weekly number of cases increased, and in week 48, the SSI announced that the incidence had reached an epidemic level. The weekly number of cases peaked in week 49 with 872 cases and then declined until week 5, after which the incidence remained consistently elevated with between 300 and 430 weekly cases, Figure 8. From week 21 in 2023 to week 20 in 2024, a total of 14,587 MP cases were recorded, of which 1,599 (11%) cases were hospitalised, which is similar to the seasons leading up to the COVID-19 pandemic. The MP incidence was highest among the 6-12-year-olds with 812 cases per 100,000, followed by the 13-19-year-olds with 535 cases per 100,000, corresponding to the distribution before the COVID-19 pandemic.

Whooping cough

Bordetella pertussis, which causes whooping cough, typically occurs with epidemics every 3 to 5 years. Epidemics were recorded in 2016, 2019 and in 2023. The level recorded in 2023 was so high that additional attention was paid to the incidence. The incidence of whooping cough was at a very low level from the spring of 2020 to the spring of 2023; initially, it was because of the COVID-19 restrictions and then, owing to a subsequent, more extended period with a very low number of cases. During that period, the incidence averaged nine confirmed monthly cases (from June 2020 to April 2023). From May 2023, the level of whooping cough started increasing, and the epidemic peaked in November 2023 with 1,665 confirmed cases, Figure 9. From the beginning of 2024, the epidemic was considered to have concluded. Whooping cough affects all age groups - the primary groups with confirmed whooping cough are older children and teenagers, very young children under one year, and adults aged 40-55 years, Figure 10. Immunity following vaccination or after a whooping cough course is not lifelong but is estimated to last 5-10 years.

The Sentinel Surveillance scheme and Virus Monitoring in Denmark monitor a range of different respiratory viruses

Sentinel

The Sentinel Surveillance scheme is based on reports from general practitioners. It is a voluntary, sample-based reporting system that monitors influenza, COVID-19 and other respiratory viral infections.

In the 2023/24 season, 114 medical practices with one or more associated doctors participated in the surveillance scheme. The sentinel doctors report weekly how many patients with influenza-like symptoms (ILS) they see in their practice and how many consultations they have in total.

From week 40/2023 to week 20/2024, an average of 135 doctors per week reported to the scheme. The proportion of patients who contacted their general practitioners with ILS was at the average level throughout autumn and winter and followed a gradually increasing trend. By December, the consultation percentage reached a high level and then declined again from January 2024. It should be noted that the consultation percentage is not specific to influenza but also reflects patients with other respiratory infections who contact their general practitioner with ILS.

The high consultation rates in weeks 52 and 13 are considered falsely elevated due to fewer reports during the holiday period, combined with fewer scheduled consultations, which is why the proportion of acute consultations due to ILS is artificially increased.

The sentinel doctors submit swabs from a subset of patients with ILS. In 2023/24, the SSI received 6,235 sentinel swabs, of which 3,331 (53%) tested positive for at least one respiratory virus.

Among the positive swabs, 945 (28%) influenza virus cases were detected. Other respiratory virus cases were found, as follows: 260 (11%) adenovirus cases, 344 (14%) RSV cases, 524 (22%) entero-/rhinovirus cases, 286 (12%) endemic coronaviruses, 602 (25%) SARS-CoV-2 cases, 160 (7%) metapneumovirus cases and 210 (9%) parainfluenza cases. The predominant viruses in the first part of the season were entero-/rhinovirus and SARS-CoV-2. These dominated until week 48, after which the influenza virus was dominant. Similar to previous seasons, the parainfluenza virus started rising towards the end of the influenza season. Similarly, a wave of metapneumovirus has been observed in spring. The distribution of respiratory viruses among sentinel swabs is summarised in Figure 12.

Virus Monitoring in Denmark

Virus Monitoring in Denmark (VMD) was established in 2023 to monitor the occurrence of respiratory infections in the general population. Various workplaces and educational institution employees and students were invited to participate. In addition, more than 200,000 Danes and their household members have been invited by Digitalmail?. In total, the VMD has 28,419 registered participants aged 5-89 years. Participants were asked to selfswab only if they had experienced symptoms of illness, which has resulted in 3,564 positive of 9,211 tested samples since week 40. SARS-CoV-2 was dominant in the autumn and winter months with 1,708 positive samples, peaking in week 49, when 315 (51%) of 616 samples were SARS-CoV-2 positive. Influenza virus was found in samples from week 46 to week 15 and peaked in week 4 with 62 positive of 283 samples (22%). Influenza A virus accounted for the overwhelming majority (98%) of all detected influenza viruses. RSV was detected from week 46 to week 8 and peaked with a positive proportion of five percent (26 positive samples) in week 50.

On 20 February 2024 and onwards, swasb from VMD were examined with the extended respiratory panel. Thus, the swabs are now being tested for the respiratory viruses employed/included? in the sentinel surveillance scheme. Since then, other coronaviruses and entero-/rhinoviruses have constituted the largest share of the positive samples. The other coronaviruses peaked in week 8 with a positivity proportion of 27 percent (68 positive samples), whereas entero-/rhinoviruses peaked in week 12 with a positivity proportion of 24 percent (61 positive samples), Figure 13.

The total weekly incidence of infections and hospitalisations with influenza, COVID-19 and RSV

The joint monitoring of respiratory pathogens has provided a better overview of how many new respiratory infections are detected weekly and their overall impact on healthcare burden due to hospital admissions. Influenza virus, RSV and Mycoplasma pneumoniae are known respiratory pathogens that circulate in the autumn and winter months, whereas Bordetella pertussis causes epidemics every 3-5 years, typically in the summer and autumn months. In addition, SARS-CoV-2 is now making a significant contribution to the total number of infections and hospitalisations. For the three major respiratory viruses SARS-CoV-2, influenza virus and RSV, the figures below show that up to and including week 50 in 2023, SARS-CoV-2 accounted for more than 50% of both laboratory-confirmed cases and hospitalisations, Figures 14 and 15. The total incidence of laboratory-confirmed cases for the three viruses peaked in the final weeks of 2023. In addition, the incidence of Bordetella pertussis and Mycoplasma pneumoniae also peaked in the final weeks of 2023, Figures 8 and 9. In early 2024, a decrease was observed in COVID-19 and RSV infections and hospitalisations along with Bordetella pertussis infections, Figure 9. While influenza infections and hospitalisations started declining as of week 6. The number of detected Mycoplasma pneumoniae cases decreased in early 2024, but the incidence was elevated throughout spring.

Vaccination coverage and vaccine effectiveness

Vaccination coverage

In the 2023/24 season, the influenza and COVID-19 vaccination scheme was operational from 1 October 2023 to 15 January 2024. The target groups for vaccination against influenza and COVID-19 largely overlap, except that children aged 2-6 years and children <2 years at increased risk are offered influenza vaccination but not COVID-19 vaccination, Table 1.

In the course of the season, the influenza and COVID-19 vaccination schemes achieved 77% coverage among those aged ≥ 65 years and 86% among nursing home residents. The coverage was somewhat lower among pregnant women in their second and third trimester (26% for influenza and 17% for COVID-19). For influenza, the group of people aged 7-64 years and <2 years at increased risk had a coverage of 29%. For COVID-19, the group of people at increased risk < 65 years recorded 18.7% coverage. For children aged 2-6 years, who were also offered the influenza vaccine, the coverage was 16%, Figures 16 and 17.

Vaccine effectiveness

Influenza

The influenza season 2023/24 was dominated by the influenza A virus, and only very few influenza B viruses were detected, which is why the influenza vaccine effectiveness (VE) is only calculated against influenza A, as an overall effect against infections and hospitalisations. For children aged 2-6 years, VE was in line with previous years, high and estimated at 63% (95% confidence interval: 54-70%). In the group of 18-64-year-olds, VE was moderate and of 41% (95% confidence interval: 37-45%). In the group of people aged 65 years or more, VE was lower of 30% (95% confidence interval: 25-34%). As in previous years, the influenza vaccine showed good effect in the 2-6-year age group, who were offered the live attenuated vaccine. In line with previous seasons, the effect of the vaccines against influenza A among adults and in the elderly age groups is more moderate.

COVID-19

The COVID-19 season 2023/24 was dominated by the XBB Omicron variant until November 2023, when Omicron BA.2.86 and its subvariant JN.1 started to dominate. The COVID-19 vaccines of the season, which targeted the XBB.1.5 variant, were offered to people above 65 years and individuals in other risk groups from 1 October 2023. The effectiveness of the vaccines against hospitalisation due to COVID-19 was calculated to be 76.1% (95% confidence interval :62.3 -84.8%) shortly after vaccination. Evidence shows that the vaccines have slightly less effect against the BA.2.86 and JN.1 variants, which later became dominant.

Influenza infection of animals and from animals to humans

No cases of animal influenza virus in humans were detected in Denmark in the 2023/24 season. However, as in the past three seasons, there have been outbreaks of highly pathogenic avian influenza (HPAI) in birds. Since 1 October 2023, outbreaks of HPAI H5N1 virus have been detected in 11 commercial poultry flocks and one hobby chicken flock. In the same period, HPAI H5N1 virus has been detected in 94 dead wild birds. Details about species, location, etc. can be found at https://ai.fvst.dk/, where avian influenza virus results are continuously reported by the SSI. The HPAI H5N1 avian influenza virus can also infect mammals and was detected in a fox found dead in January 2024. Swine influenza virus circulates endemically in Danish pigs. Data from the national swine influenza surveillance can be found here: Surveillance of Influenza A virus in Danish pigs (vetssi.dk).