Dear Editor,
Lumley et al. recently reported that, at the beginning of the COVID-19 pandemic, the usual winter 2020/2021 Respiratory Syncytial Virus (RSV) peak did not occur in Oxfordshire, UK, with an inter-seasonal rise several months later,1 as described worldwide.2, 3, 4, 5, 6 We previously described, in our French tertiary hospital, that the delayed RSV 2020/2021 outbreak involved less adults and was associated with more hospitalization, higher age of pediatric inpatients and milder median clinical phenotype than observed before the COVID-19 pandemic.2 In France, severe public restrictions (national lockdown, curfew) ended in May-June 2021, but some measures have been maintained (universal masking policy in adults and children ≥6 years in healthcare settings, schools, public transportations and most indoor spaces, educational interventions for prevention of community and healthcare-associated respiratory infections). Our study aims to evaluate (i) if these measures had an impact on the hospital burden of RSV in the 2021/2022 season when compared to the prepandemic outbreaks and (ii) if the epidemiological changes observed in 2020/2021 were also seen in 2021/2022.
All subjects admitted to Necker Hospital (Paris, France) between August 1, 2018 and February 28, 2022, with a diagnosis of RSV acute lung respiratory infection (ALRI) were included. The ALRIs was designated as nosocomial when the patient had been hospitalized ≥2 days before the onset of symptoms. The medical record of each inpatient with a positive RSV testing was examined to collect clinical and microbiological data (Supplementary data).
Overall, 1062 RSV ALRIs were diagnosed during the study period, including 1015 community-acquired infections (Table ). The 2021/2022 outbreak had similar seasonality pattern than the pre-COVID-19 outbreaks: contrary to 2020/2021 where 93.5% of cases occurred between January and March, nearly 90% of RSV ALRIs occurred between mid-October and mid-February in 2018/2020 and in 2021/2022. In pediatric units, the incidence density of community-acquired RSV ALRIs among inpatients significantly increased between 2018/2020 and 2020/2021 (8.9 versus 12.1/1000 inpatients, p = 0.0001), between 2018/2020 and 2021/2022 (8.9 versus 22/1000 inpatients, p<0.0001) and between 2020/2021 and 2021/2022 (p<0.0001). The proportion of the number of hospitalization days due to pediatric inpatients infected with community-acquired RSV among all subjects admitted during the study period was stable between 2018/2020 and 2020/2021 but increased between 2018/2020 and 2021/2022 (1.13/100 versus 2.83/100 hospitalization days, p<0.0001) and between 2020/2021 and 2021/2022 (1.56/100 versus 2.83/100 hospitalization days, p<0.0001). In adults units, the incidence density of community-acquired infections among inpatients was stable over time. After a transient decrease in 2020/2021, the proportion of hospitalization days due to adults infected with community-acquired RSV reached a similar rate in 2021/2022 than observed before the COVID-19 pandemic (data not shown). Compared to 2018/2020, the 2021/2022 outbreak had similar distribution of age categories but involved less subjects with underlying complex chronic conditions (CCC) (29.4% versus 38.8%, p = 0.008) and/or severe diseases (median length of hospital stay = 6 [4–8] versus 7 [5–9] days (p = 0.0005), admission to intensive care unit (ICU) = 32.5% versus 42.2% (p = 0.008), use of non-invasive ventilation and/or high-flow nasal oxygen = 23.6% versus 31.8%, (p<0.02)).
Table.
Comparison between characteristics and follow-up of patients admitted at Necker Hospital (Paris, France) with community-acquired RSV-associated ALRI between August 2018 and July 2020 (2018/2019 and 2019/2020 RSV outbreaks) and those of subjects admitted between August 2020 and April 2021 (2020/2021 RSV outbreak).
| 2018/2019 and 2019/2020 outbreaks(“pre-COVID-19″ outbreaks) | 2020/2021 outbreak | p* | 2021–2022 outbreak | p§ | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| August 2018 – July 2019 (n = 229) | August 2019 – July 2020 (n = 183) | Total(n = 412) | August 2020 – July 2021(n = 277) | August 2021 – February 2022 (n = 326) | ||||||||
| Rate of patients admitted with RSV ALRIs (/1000 inpatients) | ||||||||||||
| In pediatric units | 9.3 | 8.5 | 8.9 | 12.1 | <0.0001 | 22 | <0.0001 | |||||
| In adult units | 0.8 | 0.7 | 0.8 | 0.1 | 0.12 | 0.7 | 1 | |||||
| Rate of total hospitalization days due to subjects with RSV ALRIs (/100 days) | ||||||||||||
| In pediatric units | 1.81 | 1.26 | 1.55 | 1.56 | 0.8 | 2.83 | <0.0001 | |||||
| In adults units | 0.1 | 0.14 | 0.12 | 0.02 | <0.0001 | 0.08 | 0.54 | |||||
| Male sex (n,%) | 107 | (46.7) | 94 | (51.4) | 201 | (48.8) | 145 | (52.3) | 0.39 | 178 | (54.6) | 0.12 |
| Age (n,%) | ||||||||||||
| 0–5 months | 138 | (60.3) | 95 | (51.9) | 233 | (56.6) | 112 | (40.4) | <0.0001 | 175 | (53.7) | 0.46 |
| Including children born between 32 and 36 WOG | 23 | 10 | 33 | 8 | 20 | |||||||
| Including children born <32 WOG | 3 | 1 | 4 | 0 | 1 | |||||||
| 6–11 months | 27 | (11.8) | 27 | (14.8) | 54 | (13.1) | 68 | (24.5) | 0.0001 | 52 | (16.0) | 0.29 |
| 12–23 months | 23 | (10.0) | 29 | (15.8) | 52 | (12.6) | 52 | (18.8) | 0.03 | 43 | (13.2) | 0.83 |
| 2–17 years | 35 | (15.3) | 27 | (14.8) | 62 | (15.0) | 44 | (15.9) | 0.83 | 53 | (16.3) | 0.22 |
| ≥ 18 years | 6 | (2.6) | 5 | (2.7) | 11 | (2.7) | 1 | (0.4) | 0.03 | 3 | (0.9) | 0.11 |
| Underlying medical conditions (n,%) | ||||||||||||
| At least one | 94 | (41.0) | 66 | (36.1) | 160 | (38.8) | 98 | (35.4) | 0.38 | 96 | (29.4) | 0.008 |
| Neuromuscular CCC | 13 | (5.7) | 12 | (6.6) | 25 | (6.1) | 15 | (5.4) | 23 | (7.1) | ||
| Cardiovascular CCC | 21 | (9.2) | 19 | (10.4) | 40 | (9.7) | 10 | (3.6) | 9 | (2.7) | ||
| Respiratory CCC | 48 | (21.0) | 47 | (25.7) | 95 | (23.1) | 63 | (22.7) | 57 | (17.5) | ||
| Renal CCC | 7 | (3.1) | 8 | (4.4) | 15 | (3.6) | 1 | (0.4) | 7 | (2.1) | ||
| Gastrointestinal CCC | 6 | (2.6) | 6 | (3.3) | 12 | (2.9) | 6 | (2.2) | 13 | (4.0) | ||
| Hematological CCC and/or immune deficiency | 18 | (7.9) | 11 | (6.0) | 29 | (7.0) | 19 | (6.9) | 19 | (5.8) | ||
| Metabolic CCC | 2 | (0.9) | 10 | (5.5) | 12 | (2.9) | 5 | (1.8) | 9 | (2.8) | ||
| Other congenital or genetic defect | 21 | (9.2) | 15 | (8.2) | 36 | (8.7) | 16 | (5.8) | 23 | (7.1) | ||
| Antiviral prophylaxis (n,%) | 0.06 | 0.049 | ||||||||||
| Palivizumab | 6 | (2.6) | 0 | (0.0) | 6 | (1.5) | 0 | (0.0) | 1 | (0.3) | ||
| i.v. or s.c. polyvalent immunoglobulin | 3 | (1.3) | 0 | (0.0) | 3 | (0.7) | 1 | (0.4) | 0 | (0.0) | ||
| Bacterial lower respiratory tract co-/super-infection | ||||||||||||
| Microbiologically proven infection | 13 | (5.7) | 5 | (2.7) | 18 | (4.4) | 9 | (3.2) | 0.55 | 7 | (2.1) | 0.11 |
| Suspected infection | 64 | (27.9) | 78 | (42.6) | 142 | (34.5) | 92 | (33.2) | 0.74 | 121 | (37.1) | 0.49 |
| Clinical follow-up | ||||||||||||
| LOS (days) (median, IQR) | 7 | [5–9] | 7 | [5–10] | 7 | [5–9] | 6 | [4–8] | 0.0002 | 6 | [4–8] | 0.0005 |
| ICU admission (n,%) | 94 | (41.0) | 80 | (43.7) | 174 | (42.2) | 79 | (28.5) | 0.0003 | 106 | (32.5) | 0.008 |
| Oxygen requirement (n,%) | 182 | (79.5) | 151 | (82.5) | 333 | (80.8) | 217 | (78.3) | 0.44 | 246 | (75.5) | 0.09 |
| Mechanical ventilation requirement (n,%) | 8 | (3.5) | 9 | (4.9) | 17 | (4.1) | 8 | (2.9) | 0.53 | 10 | (3.1) | 0.55 |
| Non-invasive ventilation and/or high-flow nasal oxygen requirement (n,%) | 72 | (31.4) | 59 | (32.2) | 131 | (31.8) | 49 | (17.7) | <0.0001 | 77 | (23.6) | 0.02 |
| Antibiotic treatment (n,%) | 137 | (59.8) | 95 | (51.9) | 232 | (56.3) | 136 | (49.1) | 0.07 | 167 | (51.2) | 0.18 |
| Death (n,%) | 3 | (1.3) | 1 | (0.5) | 4 | (1.0) | 0 | (0.0) | 0.15 | 2 | (0.6) | 0.70 |
RSV = respiratory syncytial virus; ALRI = acute lower respiratory tract infection; WOG = weeks of gestation; CCC = chronic complex conditions; i.v. = intraveinous; s.c. = subcutaneous; LOS = length of stay; ICU = intensive care unit.
Comparison of patients admitted during the 2020/2021 outbreak versus those admitted during the “pre-COVID-19 outbreaks”.
comparison of patients admitted during the 2021/2022 outbreak versus those admitted during the “pre-COVID-19 outbreaks”.
Nosocomial RSV ALRIs were diagnosed in 47 subjects (Supplementary Table). The incidence density of nosocomial RSV ALRIs increased in pediatric units between 2018/2020 and 2021/2022 (0.31 versus 0.84/100 inpatients, p = 0.02) but was stable in adults units between study periods. Compared to community-acquired RSV, nosocomial infections were diagnosed less frequently in infants aged <6 months (17.0% versus 51.2%, p<0.0001), but more frequently in adults (21.3% versus 1.5%, p<0.0001), subjects with underlying CCC (87.2% versus 34.9%, p<0.0001) and subjects requiring ICU admission (87.2% versus 35.4%, p<0.001). The death rate (whatever the cause of death) was higher in subjects with nosocomial RSV ALRIs than in those admitted with community-acquired infections (4.3 versus 0.6%, p = 0.045).
Despite the maintain of some public health measures in France and the repeated educational interventions for prevention of respiratory infections in the community, the RSV 2021/2022 outbreak occurred with a higher proportion of hospitalization days due to community-acquired ALRIs compared to what observed during the pre-COVID-19 era. Our study highlights the great fragility of RSV control in the population and the fact that, except in case of extreme measures such as national lockdown, primary prevention measures are not sufficient to significantly decrease the hospital burden of community RSV ALRIs.
In 2021/2022, the distribution of age categories returned to similar values as observed during pre-COVID-19 outbreaks. However, the proportion of subjects with underlying CCC was significantly lower in 2021/2022 than in 2018/2020, which could, at less partly, explain the lower median severity of RSV infections during the recent outbreak. Two hypotheses could explain this finding. First, the cohort of RSV-naïve individuals was probably still larger in 2021/2022 than during the pre-COVID-19 era, leading to a higher incidence of RSV ALRIs in the general pediatric population (even in children without CCC). Second, individuals with CCC could be more sensitive to prevention messages about infection control, diffused repeatedly since the emergence of SARS-CoV-2, compared to the general population. Further studies are needed during future RSV outbreaks in order to evaluate if an impact of hygiene measures can be seen durably in individuals with CCC.
Compared to the pre-COVID-19 era, the recent RSV outbreak was characterized by a higher density incidence of nosocomial ALRIs in pediatric units. However the percentage of nosocomial infections among all diagnosed RSV ALRIs remained lower in our center than in previous pediatric studies (3.7% versus 5–6%).7 , 8 Thus, no clear impact of reinforced hygiene measures taken during the COVID-19 pandemic was seen in our center, in the context of a pre-existing low rate of nosocomial RSV infections due to our multifaceted infection control strategy. Despite these encouraging findings, sustained efforts are required to prevent nosocomial RSV infections in adult units. Indeed, the proportion of adults with nosocomial infections was disproportionately higher than that of adults admitted with community-acquired ALRIs. Finally, the higher death rate observed in subjects with nosocomial ALRIs than in those with community-acquired infections was in line with studies suggesting a higher severity of nosocomial RSV infections.8 , 9
Because RSV may not have been screened in all patients with ALRI, this study may underestimate the real burden of RSV infection in our center. This underestimation may be more pronounced in patients with milder symptoms, where RSV may have been less frequently screened than in case of severe infection.
To conclude, current public health measures, although intensified compared to the pre-COVID-19 era, did not mitigate the hospital burden of RSV in 2021/2022. The identification of new preventive strategies targeted to the RSV reservoir in the population is urgently needed.
Funding
This study was carried out as part of our routine work.
Ethics
Participants provided informed consent for the anonymous use of their clinical and biological data for biomedical research and publication (for pediatric patients, informed consent was provided by parents/guardians). This study was reviewed and approved by the Necker Hospital Institutional Review Board (registration number in the registry of the Assistance Publique – Hôpitaux de Paris: 20190729122906).
Authors’ contribution
JF and PF conceived the study and drafted the manuscript; JT, HC, CD, FM, PP, AS, HA and MLV provided contribution to the analysis of the data and the revision of the manuscript. All authors approved the final version to be published and agreed to be accountable for all aspects of the work.
Declaration of Competing Interest
Authors report no potential conflicts in relation to this article. P.F. has received honoraria and travel grants from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD France for participation in advisory boards, educational programs, and conferences, outside the submitted work. M. L.-V. has received nonfinancial and other support from BioMérieux and nonfinancial support from Abbott and Ferring SAS, outside the submitted work.
Footnotes
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.jinf.2022.06.019.
Appendix. Supplementary materials
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