Burden of respiratory syncytial virus infection in older and high-risk adults: a systematic review and meta-analysis of the evidence from developed countries

Abstract

Background: Respiratory syncytial virus (RSV) significantly impacts the health of older and high-risk adults (those with comorbidities). We aimed to synthesise the evidence on RSV disease burden and RSV-related healthcare utilisation in both populations.

Methods: We searched Embase and MEDLINE for papers published between 2000 and 2019 reporting the burden and clinical presentation of symptomatic RSV infection and the associated healthcare utilisation in developed countries in adults aged ≥60 years or at high risk. We calculated pooled estimates using random-effects inverse variance-weighted meta-analysis.

Results: 103 out of 3429 articles met the inclusion criteria. Among older adults, RSV caused 4.66% (95% CI 3.34-6.48%) of symptomatic respiratory infections in annual studies and 7.80% (95% CI 5.77-10.45%) in seasonal studies; RSV-related case fatality proportion (CFP) was 8.18% (95% CI 5.54-11.94%). Among high-risk adults, RSV caused 7.03% (95% CI 5.18-9.48%) of symptomatic respiratory infections in annual studies, and 7.69% (95% CI 6.23-9.46%) in seasonal studies; CFP was 9.88% (95% CI 6.66-14.43%). Data paucity impaired the calculation of estimates on population incidence, clinical presentation, severe outcomes and healthcare-related utilisation.

Conclusions: Older and high-risk adults frequently experience symptomatic RSV infection, with appreciable mortality; however, detailed data are lacking. Increased surveillance and research are needed to quantify population-based disease burden and facilitate RSV treatments and vaccine development.

FIGURE 1

Proportion of respiratory infections attributable to respiratory syncytial virus (RSV) among older adults: a) annual and b) seasonal studies. For each study, the first author, publication year, country of study, participants’ age group, population type, sampling method and respiratory infection, risk-of-bias assessment results (ROB), positive RSV cases, tested samples, proportion of RSV cases (expressed as %) and its 95% confidence interval is given. Estimates stratified by data collection period, population according to the study setting and age are shown. NL: the Netherlands; US: United States of America; FR: France; IT: Italy; AU: Australia; ES: Spain; JP: Japan; FI: Finland; CH: Switzerland; EE: Estonia; UK: United Kingdom; BE: Belgium; CA: Canada; PL: Poland; DE: Germany; NO: Norway; CZ: Czech Republic; PT: Portugal; GR: Greece; REM: random-effect model; Q: Cochran's Q-test; I²: I² statistic; SS: systematic sampling; ARI: acute respiratory infection; CI: sampling by clinical indication; IP: inpatients; ILI: influenza-like illness; SARI: severe ARI; ED: emergency department; OP: outpatients; ICU: intensive care unit; PNM: pneumonia; MSARI: moderate to severe ARI; MSILI: moderate to severe ILI; FLUVAC: influenza-vaccinated study population. ^#: sampling targeted at inpatients with respiratory distress, immunocompromised or critically ill; ^¶: CAPITA trial, no active community-based follow-up, cases detected from medical facilities; ⁺: very high rates of underlying comorbidities; ^§: emergency hospitalisations; ^ƒ: fever and cough included in eligibility criteria most seasons; ^##: swabbing conducted during influenza season.

FIGURE 2

Case fatality proportion among respiratory syncytial virus (RSV)-positive older adults. For each study, the first author, publication year, country of study, participants’ age group, population type, sampling method and respiratory infection, risk-of-bias assessment results (ROB), number of deaths, number of positive RSV cases, total sample size (Total), proportion of deaths among RSV cases (expressed as %) and its 95% confidence interval is given. Estimates stratified by data collection period are shown. US: United States of America; ES: Spain; FR: France; AU: Australia; REM: random-effect model; Q: Cochran's Q-test; I²: I² statistic; SS: systematic sampling; ARI: acute respiratory infection; IP: inpatients; ILI: influenza-like illness; CI: sampling by clinical indication; ED: emergency department; PNM: pneumonia. ^#: emergency hospitalisations.

FIGURE 3

Proportion of respiratory infections attributable to respiratory syncytial virus (RSV) among high-risk adults: a) annual and b) seasonal studies. For each study, the first author, publication year, country of study, participants’ age group, study setting, population type, sampling method and respiratory infection, risk-of-bias assessment results (ROB), positive RSV cases, tested samples, proportion of RSV cases (expressed as %) and its 95% confidence interval is given. Estimates stratified by data collection period and high-risk subgroups are shown. JP: Japan; AU: Australia; US: United States of America; CH: Switzerland; UK: United Kingdom; DE: Germany; GR: Greece; PL: Poland; ES: Spain; BE: Belgium; CA: Canada; IT: Italy; NL: the Netherlands; FR: France; PT: Portugal; REM: random-effect model; Q: Cochran's Q-test; I²: I² statistic; meda: medically attended; comm: community-based; SS: systematic sampling; AEA: acute exacerbation of asthma; ED: emergency department; PNM: pneumonia; IP: inpatients; CI: sampling by clinical indication; AEC: acute exacerbation of COPD; ICU MV: intensive care unit, mechanically ventilated; OP: outpatients; ARI: acute respiratory infection; RVI: respiratory virus infection; ILI: influenza-like illness; URTI: upper respiratory tract infection; RF: respiratory failure; CCU: critical care unit; LRTI: lower respiratory tract infection; CKD: chronic kidney disease; CVD: cardiovascular disease. ^#: excluded COPD, pneumonia, interstitial lung diseases and acute heart failure patients, as well as those with respiratory symptoms due to infections in the past month; ^¶: included immunocompromised patients with suspicion of infection and/or respiratory symptoms and/or radiologically confirmed lung infiltrates undergoing bronchoscopy; ⁺: patients followed in medical facility; ^§: inclusion criteria: acute exacerbation of chronic cardiopulmonary illness or acute pulmonary illness (pneumonia, bronchitis, ILI); ^ƒ: fever and cough included in eligibility criteria most seasons; ^##: emergency hospitalisations; ^¶¶: all inpatient haematopoietic stem cell transplant patients enrolled, regardless of whether they had symptoms; ⁺⁺: recruitment during summer.

FIGURE 4

Case fatality proportion among respiratory syncytical virus (RSV)-positive high-risk groups. For each study, the first author, publication year, country of study, participants age group, study setting, population type, sampling method and respiratory infection, risk-of-bias assessment results (ROB), number of deaths, positive RSV cases, total sample size and proportion of deaths among RSV cases (expressed as %) and its 95% confidence interval is given. Estimates stratified by high-risk subgroups are shown. US: United States of America; NL: the Netherlands; FR: France; ES: Spain; AU: Australia; IT: Italy; CH: Switzerland; REM: random-effect model; Q: Cochran's Q-test; I²: I² statistic; comm: community-based; meda: medically attended; SS: systematic sampling; ARI: acute respiratory infection; ICU: intensive care unit; RF: respiratory failure; IP: inpatients; CI: sampling by clinical indication; ILI: influenza-like illness; RVI: respiratory viral infection; OP: outpatients. ^#: patients sampled based on clinical indication, but all RSV positives systematically included in analysis; ^¶: patients followed in medical facility.