Sustained reductions in life-threatening invasive bacterial diseases during the first two years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries participating in the IRIS Consortium

Background The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Streptococcus agalactiae . Here we analyse the incidence and distribution of disease during the first two years of the pandemic. Methods Laboratories in 30 countries/territories representing five continents submitted case data from 2018-2021 to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype/group were examined. Interrupted time series analyses quantified the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models estimated effect sizes and forecasted counterfactual trends by hemisphere. Findings Overall, 116,841 cases were analysed: 76,481 (2018-2019, pre-pandemic) plus 40,360 (2020-2021, pandemic). During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio: 0.47; 95% confidence interval: 0.40-0.55), H influenzae (0.51; 0.40-0.66) and N meningitidis (0.26; 0.21-0.31), whereas no significant changes were observed for the non-respiratory-transmitted pathogen S agalactiae (1.02; 0.75-1.40). No major changes in the distribution of cases were observed when stratified by patient age or serotype/group. An estimated 36,289 (17,145-55,434) cases of invasive bacterial disease were averted during the first two years of the pandemic among IRIS participating countries/territories. Interpretation COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae and N meningitidis during the first two years of the pandemic, but cases began to increase in some countries as pandemic restrictions were lifted. Evidence before this study Early in the COVID-19 pandemic the IRIS Consortium reported a significant reduction in invasive disease due to respiratory-transmitted bacterial pathogens, which was associated with the implementation of COVID-19 stringency measures and changes in human social behaviour. All 26 countries/territories participating in IRIS at the time experienced a significant reduction in infections between January and May 2020, compared with the previous two years. In particular, S pneumoniae infections decreased by 68% at four weeks after COVID-19 containment measures were imposed, and by 82% at eight weeks. Added value of this study These new data from the expanded IRIS Consortium across 30 countries/territories demonstrated a sustained reduction in invasive disease throughout the first two years of the COVID-19 pandemic. Using time series modelling, we estimated that over 36,000 cases of invasive bacterial disease were averted in 2020-2021 among the countries participating in IRIS; however, minor increases in disease in the latter half of 2021 require close monitoring to understand the nature of re-emerging cases. Implications of all the available evidence Future epidemics and pandemics will occur, and we need to understand not only the pathogen that is directly responsible for the pandemic, but also that population-level responses to an epidemic or pandemic more broadly affect overall human health and other microbes. IRIS provides evidence for the effects of such public health responses on severe invasive bacterial infections across many countries. Moreover, these IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to healthcare service planning and provision of policies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The infrastructure for the IRIS Consortium is funded by a Wellcome Trust Investigator Award to ABB (grant number 206394/Z/17/Z). The IRIS databases are part of PubMLST, which is funded by a Wellcome Trust Biomedical Resource Grant awarded to MJCM, ABB, and KAJ (grant number 218205/Z/19/Z). DS is funded by an Oxford Clarendon Scholarship. The high-performance computing requirements of the data analyses were supported by the Wellcome Trust Core Award (grant number 203141/Z/16/Z) and the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Authors were not precluded from accessing data in the study, and they accept responsibility to submit for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: A waiver of ethical approval was received from the Chair of the Oxford Ethical Committee (Dr. Kevin Marsh). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Sharing study data is not possible because of the risk of identifying individual cases of invasive disease in some countries.