Does the rise in seasonal respiratory viruses foreshadow the return of invasive pneumococcal disease this winter?

Abstract

Early in the COVID-19 pandemic, there were concerns that the introduction of the novel respiratory virus, SARS-CoV-2, would lead to a rise in secondary bacterial infections, especially pneumococcal disease, which has been associated with high fatality rates in previous influenza pandemics. In particular, early reports of hospitalised patients in China found that 50% of COVID-19 non-survivors had bacterial co-infection compared with 15% of survivors.1Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Summary Full Text Full Text PDF PubMed Scopus (15086) Google Scholar Fortunately, the first pandemic peak saw huge declines in, or in some cases, complete suppression of infections caused by many pathogens, including Streptococcus pneumoniae.2Brueggemann AB Jansen van Rensburg MJ Shaw D et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3: e360-e370Summary Full Text Full Text PDF PubMed Scopus (85) Google Scholar In England, cases of invasive pneumococcal disease declined by 30%, from 5666 in the 2018–19 epidemiological year (ie, July–June) to 3964 in 2019–20.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Additionally, co-infections (n=40) or secondary COVID-19 after invasive pneumococcal disease (n=27) were rare but associated with a high fatality.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google ScholarIt was posited that these declines were probably due to the interruption of person-to-person transmission of S pneumoniae because of government stay-at-home orders, physical distancing, and increased infection control measures to reduce the spread of SARS-CoV-2.2Brueggemann AB Jansen van Rensburg MJ Shaw D et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3: e360-e370Summary Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Contemporaneous reductions in respiratory viral infections will have also reduced the risk of secondary pneumococcal infections.4Danino D Ben-Shimol S van der Beek BA et al.Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study.medRxiv. 2021; (published online Aug 1.) (preprint).https://doi.org/10.1101/2021.07.29.21261308Google Scholar Interestingly, nasopharyngeal pneumococcal carriage rates in children reduced only slightly during the pandemic in Israel, while serotype distribution remained similar to pre-pandemic years.4Danino D Ben-Shimol S van der Beek BA et al.Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study.medRxiv. 2021; (published online Aug 1.) (preprint).https://doi.org/10.1101/2021.07.29.21261308Google ScholarAs the winter season approaches, we compared cases of invasive pneumococcal disease in England from 2020–21 to the 3 previous epidemiological years. In England, the first SARS-CoV-2 cases were detected in January, 2020, and increased rapidly from March, 2020, leading to a national lockdown that included school closures. Lockdown was eased during the summer but was re-implemented in November, 2020, and January, 2021, with gradual easing from March, 2021, and removal of all mitigations from July 19, 2021. Invasive pneumococcal disease surveillance in England has been described previously.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Briefly, National Health Service hospitals electronically report all infections and routinely submit invasive pneumococcal isolates for serotyping to Public Health England (now known as the UK Health Security Agency). In the UK, the 23-valent pneumococcal polysaccharide vaccine (PPV23) is offered to all individuals aged 65 years or older and children with comorbidities aged 2 years or older, while the 13-valent pneumococcal conjugate vaccine (PCV13) has been offered to infants at a 2+1 schedule (ie, at 8 weeks, 16 weeks, and 1 year) since 2010 and replaced with a 1+1 schedule at 12 weeks and 1 year since Jan 1, 2020.5Ladhani SN Andrews N Ramsay ME Summary of evidence to reduce the two-dose infant priming schedule to a single dose of the 13-valent pneumococcal conjugate vaccine in the national immunisation programme in the UK.Lancet Infect Dis. 2021; 21: e93-102Summary Full Text Full Text PDF PubMed Scopus (5) Google ScholarCases of invasive pneumococcal disease declined from March, 2020, reaching a nadir in February, 2021, when they accounted for 8% of the pre-pandemic 3-year average for February. Since then, cases have increased gradually, such that, by June, 2021, they were only 25% lower than the pre-pandemic 3-year average for June (figure 1A). The annual incidence of invasive pneumococcal disease in 2020–21 was 3 per 100 000 compared with the pre-pandemic 3-year average of 11 per 100 000. Serotype distribution was similar to pre-pandemic years (figure 1B), with a non-significant decline of 5·7% in PPV23-type invasive pneumococcal disease—largely due to reductions in serotype 12F—but the proportion of cases was significantly higher in children older than 5 years (8·7% [95% CI 7·3–10·2] vs 4·6% ([4·3–4·9]) and lower in those aged 85 years or older (11·2% [9·6–13·0] vs 16·1% [15·6–16·7]) compared with pre-pandemic years (figure 1C). This difference might be due to various factors, including continued educational and social mixing among children, whereas older adults remained largely shielded. Among children older than 1 year who were eligible for the 1+1 PCV13 schedule, there were 35 cases of invasive pneumococcal disease from April, 2020, to March, 2021, including six (17%) due to PCV13-serotypes (three with serotype 19A, two with serotype 3, and one with serotype 19F).In England, the gradual increase in cases of invasive pneumococcal disease following resumption of normal social activities has been associated with increased reporting of viral infections outside their typical seasonality, including respiratory syncytial virus, which started increasing in May, 2021, and peaked in August, 2021, instead of the typical annual peaks every December.6Public Health EnglandWeekly national flu and COVID-19 surveillance reports published.https://www.gov.uk/government/news/weekly-national-flu-and-covid-19-surveillance-reports-published#historyDate: Oct 15, 2020Date accessed: October 18, 2021Google Scholar There are also concerns about potentially higher-than-average surges in respiratory viral infections (especially influenza) this coming winter, because of the population immunity debt following 18 months of lockdown and social isolation.7Cohen R Ashman M Taha M-K et al.Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap?.Infectious Dis Now. 2021; 51: 418-423Crossref PubMed Scopus (34) Google Scholar For this reason, the UK extended recommendations for influenza vaccination to include all children aged 2–15 years on Aug 31, 2021, and every effort is being made to maximise vaccine uptake, including PPV23 for those aged 65 years or older and those with comorbidities.8Djennad A Ramsay ME Pebody R et al.Effectiveness of 23-valent polysaccharide pneumococcal vaccine and changes in invasive pneumococcal disease incidence from 2000 to 2017 in those aged 65 and over in England and Wales.EClinicalMedicine. 2019; 6: 42-50Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 9Department of Health and Social CareNHS EnglandPublic Health EnglandGuidance: national flu immunisation programme, 2021 to 2022 letter.https://www.gov.uk/government/publications/national-flu-immunisation-programme-plan/national-flu-immunisation-programme-2021-to-2022-letterDate: July 17, 2021Date accessed: October 18, 2021Google Scholar High pneumococcal and influenza vaccine uptake is important: a person is 8 times more likely to die within 30 days if they are co-infected with invasive pneumococcal disease and SARS-CoV-2 than if they are infected with invasive pneumococcal disease alone; they are 6 times more likely to die if they are co-infected with influenza and SARS-CoV-2 compared with having neither of these infections.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar, 10Stowe J Tessier E Zhao H et al.Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design.Int J Epidemiol. 2021; 50: 1124-1133Crossref PubMed Scopus (50) Google Scholar In conclusion, after the first winter season and three COVID-19 waves in England, cases of invasive pneumococcal disease remained reassuringly low across all age groups, confirming a low risk of invasive pneumococcal disease with or after SARS-CoV-2 infection. Ongoing surveillance will be crucial now that all mitigations are removed in England. Early in the COVID-19 pandemic, there were concerns that the introduction of the novel respiratory virus, SARS-CoV-2, would lead to a rise in secondary bacterial infections, especially pneumococcal disease, which has been associated with high fatality rates in previous influenza pandemics. In particular, early reports of hospitalised patients in China found that 50% of COVID-19 non-survivors had bacterial co-infection compared with 15% of survivors.1Zhou F Yu T Du R et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Summary Full Text Full Text PDF PubMed Scopus (15086) Google Scholar Fortunately, the first pandemic peak saw huge declines in, or in some cases, complete suppression of infections caused by many pathogens, including Streptococcus pneumoniae.2Brueggemann AB Jansen van Rensburg MJ Shaw D et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3: e360-e370Summary Full Text Full Text PDF PubMed Scopus (85) Google Scholar In England, cases of invasive pneumococcal disease declined by 30%, from 5666 in the 2018–19 epidemiological year (ie, July–June) to 3964 in 2019–20.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Additionally, co-infections (n=40) or secondary COVID-19 after invasive pneumococcal disease (n=27) were rare but associated with a high fatality.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar It was posited that these declines were probably due to the interruption of person-to-person transmission of S pneumoniae because of government stay-at-home orders, physical distancing, and increased infection control measures to reduce the spread of SARS-CoV-2.2Brueggemann AB Jansen van Rensburg MJ Shaw D et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3: e360-e370Summary Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Contemporaneous reductions in respiratory viral infections will have also reduced the risk of secondary pneumococcal infections.4Danino D Ben-Shimol S van der Beek BA et al.Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study.medRxiv. 2021; (published online Aug 1.) (preprint).https://doi.org/10.1101/2021.07.29.21261308Google Scholar Interestingly, nasopharyngeal pneumococcal carriage rates in children reduced only slightly during the pandemic in Israel, while serotype distribution remained similar to pre-pandemic years.4Danino D Ben-Shimol S van der Beek BA et al.Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study.medRxiv. 2021; (published online Aug 1.) (preprint).https://doi.org/10.1101/2021.07.29.21261308Google Scholar As the winter season approaches, we compared cases of invasive pneumococcal disease in England from 2020–21 to the 3 previous epidemiological years. In England, the first SARS-CoV-2 cases were detected in January, 2020, and increased rapidly from March, 2020, leading to a national lockdown that included school closures. Lockdown was eased during the summer but was re-implemented in November, 2020, and January, 2021, with gradual easing from March, 2021, and removal of all mitigations from July 19, 2021. Invasive pneumococcal disease surveillance in England has been described previously.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar Briefly, National Health Service hospitals electronically report all infections and routinely submit invasive pneumococcal isolates for serotyping to Public Health England (now known as the UK Health Security Agency). In the UK, the 23-valent pneumococcal polysaccharide vaccine (PPV23) is offered to all individuals aged 65 years or older and children with comorbidities aged 2 years or older, while the 13-valent pneumococcal conjugate vaccine (PCV13) has been offered to infants at a 2+1 schedule (ie, at 8 weeks, 16 weeks, and 1 year) since 2010 and replaced with a 1+1 schedule at 12 weeks and 1 year since Jan 1, 2020.5Ladhani SN Andrews N Ramsay ME Summary of evidence to reduce the two-dose infant priming schedule to a single dose of the 13-valent pneumococcal conjugate vaccine in the national immunisation programme in the UK.Lancet Infect Dis. 2021; 21: e93-102Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar Cases of invasive pneumococcal disease declined from March, 2020, reaching a nadir in February, 2021, when they accounted for 8% of the pre-pandemic 3-year average for February. Since then, cases have increased gradually, such that, by June, 2021, they were only 25% lower than the pre-pandemic 3-year average for June (figure 1A). The annual incidence of invasive pneumococcal disease in 2020–21 was 3 per 100 000 compared with the pre-pandemic 3-year average of 11 per 100 000. Serotype distribution was similar to pre-pandemic years (figure 1B), with a non-significant decline of 5·7% in PPV23-type invasive pneumococcal disease—largely due to reductions in serotype 12F—but the proportion of cases was significantly higher in children older than 5 years (8·7% [95% CI 7·3–10·2] vs 4·6% ([4·3–4·9]) and lower in those aged 85 years or older (11·2% [9·6–13·0] vs 16·1% [15·6–16·7]) compared with pre-pandemic years (figure 1C). This difference might be due to various factors, including continued educational and social mixing among children, whereas older adults remained largely shielded. Among children older than 1 year who were eligible for the 1+1 PCV13 schedule, there were 35 cases of invasive pneumococcal disease from April, 2020, to March, 2021, including six (17%) due to PCV13-serotypes (three with serotype 19A, two with serotype 3, and one with serotype 19F). In England, the gradual increase in cases of invasive pneumococcal disease following resumption of normal social activities has been associated with increased reporting of viral infections outside their typical seasonality, including respiratory syncytial virus, which started increasing in May, 2021, and peaked in August, 2021, instead of the typical annual peaks every December.6Public Health EnglandWeekly national flu and COVID-19 surveillance reports published.https://www.gov.uk/government/news/weekly-national-flu-and-covid-19-surveillance-reports-published#historyDate: Oct 15, 2020Date accessed: October 18, 2021Google Scholar There are also concerns about potentially higher-than-average surges in respiratory viral infections (especially influenza) this coming winter, because of the population immunity debt following 18 months of lockdown and social isolation.7Cohen R Ashman M Taha M-K et al.Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap?.Infectious Dis Now. 2021; 51: 418-423Crossref PubMed Scopus (34) Google Scholar For this reason, the UK extended recommendations for influenza vaccination to include all children aged 2–15 years on Aug 31, 2021, and every effort is being made to maximise vaccine uptake, including PPV23 for those aged 65 years or older and those with comorbidities.8Djennad A Ramsay ME Pebody R et al.Effectiveness of 23-valent polysaccharide pneumococcal vaccine and changes in invasive pneumococcal disease incidence from 2000 to 2017 in those aged 65 and over in England and Wales.EClinicalMedicine. 2019; 6: 42-50Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 9Department of Health and Social CareNHS EnglandPublic Health EnglandGuidance: national flu immunisation programme, 2021 to 2022 letter.https://www.gov.uk/government/publications/national-flu-immunisation-programme-plan/national-flu-immunisation-programme-2021-to-2022-letterDate: July 17, 2021Date accessed: October 18, 2021Google Scholar High pneumococcal and influenza vaccine uptake is important: a person is 8 times more likely to die within 30 days if they are co-infected with invasive pneumococcal disease and SARS-CoV-2 than if they are infected with invasive pneumococcal disease alone; they are 6 times more likely to die if they are co-infected with influenza and SARS-CoV-2 compared with having neither of these infections.3Amin-Chowdhury Z Aiano F Mensah A et al.Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England.Clin Infect Dis. 2021; 72: e65-e75Crossref PubMed Scopus (54) Google Scholar, 10Stowe J Tessier E Zhao H et al.Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design.Int J Epidemiol. 2021; 50: 1124-1133Crossref PubMed Scopus (50) Google Scholar In conclusion, after the first winter season and three COVID-19 waves in England, cases of invasive pneumococcal disease remained reassuringly low across all age groups, confirming a low risk of invasive pneumococcal disease with or after SARS-CoV-2 infection. Ongoing surveillance will be crucial now that all mitigations are removed in England. CLS, SE, DL, and NKF report payment to their institution for investigator-led research in pneumococcal pneumonia or carriage, or both, in humans by GlaxoSmithKline and Pfizer. All other authors declare no competing interests.