Predictors of Hospitalization and Superinfection in Viral Respiratory Tract Infections Between Influenza and Paramyxoviruses: The SUPERFLUOUS Study
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
The Journal of Infectious Diseases
MAJOR ARTICLE
Predictors of Hospitalization and Superinfection in Viral
Respiratory Tract Infections Between Influenza and
Paramyxoviruses: The SUPERFLUOUS Study
Benoit Lemarie,1 Ghilas Boussaid,2 Elyanne Gault,3 Helene Prigent,4 Sebastien Beaune,5 Frederique Moreau,3 Jennifer Dumoulin,6 Marion Pepin,7
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
Segolene Greffe,8 Pierre De Truchis,1 and Benjamin Davido1,
1
Maladies Infectieuses, Hôpital Raymond Poincaré, Garches, France, 2Université Paris-Saclay, Université Versailles Saint-Quentin, Equipe de Recherche Paramédicale sur le HAndicap Neuromoteur,
Versailles, France, 3Virologie, Hôpital Ambroise-Paré, AP-HP, Boulogne-Billancourt, France, 4Exploration Fonctionnelles Respiratoires, Hôpital Raymond-Poincaré, AP-HP, Garches, France, 5Service
d’Accueil des Urgences, Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France, 6Pneumologie, Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France, 7Gériatrie, Hôpital Ambroise Paré,
AP-HP, Boulogne-Billancourt, France, and 8Médecine Interne, Hôpital Ambroise Paré, AP-HP, Boulogne-Billancourt, France
Background. Viral respiratory tract infections (VRTIs) are among the most common diseases, but the risks of superinfection for
different virus species have never been compared.
Methods. Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription pol-
ymerase chain reaction. We compared characteristics between influenza (A or B) and paramyxoviruses (respiratory syncytial virus,
parainfluenza virus types 1 and 3, and human metapneumovirus) and identified predictors of superinfection and hospitalization.s
Results. Five hundred ninety patients had VRTI, including 347 (59%) influenza and 243 paramyxovirus infections with
comparable rates of superinfections (53% vs 60%). In multivariate analyses, the predictors of superinfections were age >75 years
(adjusted odds ratio, 2.37 [95% confidence interval, 1.65–3.40]), chronic respiratory disease (1.79 [1.20–2.67]), and biological ab-
normalities, including neutrophil count >7000/µL (1.98 [1.34–2.91)], eosinophil count 0.25 ng/mL (2.8 [1.65–4.73]). The predictors of hospitalization were age >75 years old (adjusted odds ratio, 3.49 [95% confi-
dence interval, 2.17–5.63]), paramyxovirus infection (2.28 [1.39–3.75]), long-term use of inhaled corticosteroids (2.49 [1.13–5.49]),
and biological abnormalities, including neutrophil count >7000/µL (2.38 [1.37–4.12)] and procalcitonin level >0.25 ng/mL (2.49
[1.23–5.02]). Kaplan-Meier survival curves showed that influenza-infected patients had a higher mortality rate than those with par-
amyxovirus infections (8.9% vs 4.5%, respectively; P = .02).
Conclusions. Our study revealed a high rate of superinfection (56%), not related to viral species. However influenza virus was
associated with a poorer prognosis than paramyxoviruses, pleading for a broader and large-scale vaccination of individual at risk of
VRTIs.
Keywords. Bacteria; influenza; respiratory tract infections; Superinfection; Viruses.
Lower respiratory tract infections (LRTIs) are among the most epidemics and the recent pandemic of coronavirus dis-
common infections in adults and among the largest burdens ease 2019 (COVID-19) illustrate the capabilities of viruses.
on health systems. World Health Organization estimates pneu- Templeton et al [3] estimated that the rate of microbiological
monia is responsible for about 2.5 million deaths each year documentation in LRTIs has increased from 49.5% with usual
worldwide [1]. Considering its serious consequences on an in- techniques to 76% with polymerase chain reaction (PCR) in
dividual scale, pneumonia has also a major economic impact, the last decade.
with an annual cost in developed countries estimated at €10 bil- Viral infections can represent 40%–56.3% of community-
lion in Europe [2]. acquired pneumonia [4]. Seasonal influenza was responsible
Historically, pneumonia was deemed to have a bacterial or- for 3.8% of all admissions for respiratory failure between
igin . Nowadays, viruses are also recognized as microorgan- 2003 and 2009 in North America [5]. A better approach to
isms capable of causing LRTIs. Indeed, annual influenza viral respiratory tract infections (VRTIs) considers the inter-
actions between viruses and bacteria inside the lower respi-
ratory tract. The concept of superinfection is well known and
Received 23 June 2021; editorial decision 6 October 2021; accepted 8 October 2021; published illustrates the fact that a VRTI can facilitate the onset of a
online 12 October 2021.
bacterial pneumonia. Superinfections have been associated
Correspondence: Benjamin Davido, Raymond Poincare Hospital, 104 boulevard Raymond-
Poincaré, 92380 Garches, France (benjamin.davido@aphp.fr). with a large majority of deaths during the Spanish flu pan-
The Journal of Infectious Diseases® 2021;XX:1–9 demic [6] and with epidemiological correlations between
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society
annual influenza epidemics and an increased incidence of
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
https://doi.org/10.1093/infdis/jiab525 pneumococcal pneumonia [7]. Beyond epidemiological
Bacterial Superinfection Among Viruses • JID 2021:XX (XX XX) • 1evidence, the mechanisms of interactions between influenza Laboratory Findings
and Streptococcus pneumoniae have already been studied [8]. The patient cohort was extracted from the virology laboratory
Indeed, the virus can promote a superinfection in many ways: GLIMS database. Reverse-transcription PCR was originally a
by altering passive defenses of the lung and innate immunity, homemade technique, developed by the virology laboratory of
by inhibiting or diverting adaptive immunity, or by directly Ambroise-Paré Hospital [14]. It was based on the simultaneous
promoting bacterial virulence and invasiveness [9, 10]. In ad- realization of 3 triplex PCRs: one each for influenza A and B
dition, there is evidence of synergism between bacteria and and RSV; for PIV-1, PIV-3, and hMPV; and for Mycoplasma
influenza virus, but also with other respiratory viruses, such as pneumoniae, Chlamydia pneumoniae, and a positive control
respiratory syncytial virus (RSV), human metapneumovirus using albumin. This technique was replaced during night shift
(hMPV), and rhinoviruses [11, 12]. or the weekend by a CEPHEID kit test, testing exclusively for
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
However, the prevalence of superinfection in a given pop- influenza virus and RSV. To clarify findings, viruses were clas-
ulation according to the viral species remains unclear. To our sified according to their species: influenza viruses (influenza A
knowledge, it has only been described in hospitalized patients and B) and paramyxoviruses (RSV, hMPV, PIV-1, and PIV-3).
with noninfluenza VRTI by Chen et al [13], and it has not re-
Data Collection and Definitions
vealed any specificity for any viral species. Tackling this sub-
ject better might lead to a more appropriate use of antibiotics For every patient, we collected epidemiological data: sex, age,
by reducing their prescription, especially during the fall-winter underlying conditions (including Charlson comorbidity index
season. The aim of the present study was to characterize the rate [CCI] and the presence of immunosuppression, defined as the
of superinfection among adults according to viral species and to presence of active cancer within the last 5 years, HIV infec-
determine whether there are particular factors associated with tion, or immunosuppressive therapy, including corticosteroids
superinfection and their outcomes. at >5 mg/d), smoking and vaccination status, the presence of
bacterial bronchial colonization, and long-term use of inhaled
corticosteroids (ICSs) or azithromycin. We also collected data
METHODS concerning the current infectious episode, including date of
Patient Characteristics symptom onset; categorization as community acquired, hos-
We conducted a retrospective multicenter cohort study in the pital acquired or care related (defined as a situation of regular
hospital group of the Paris-Saclay Ile-de-France University, ambulatory hospital care, such as day hospital or hemodialysis);
France, from October 2016 to June 2018. Data from the vi- need for hospitalization and length of stay; outcomes at days
rology laboratory were obtained to identify all adult patients 7, 30, and 90 after testing; biological, microbiological, and ra-
who had PCR evidence of a respiratory tract infection (RTI) diological findings, and Fine score. Finally, we collected data
and were positive for any of the following viruses: influenza A on therapeutics used (antibiotics and antiviral agents, such as
or B virus, RSV, hMPV, and parainfluenza virus (PIV) type 1 oseltamivir) and the duration of therapy.
(PIV-1) or 3 (PIV-3).
Definitions
A certain superinfection was defined as a viral episode asso-
Hospital Setting ciated with documented bacterial infection (documented by
This retrospective study was conducted in the Paris-Saclay blood or sputum culture, antigenuria, or intracellular bacterial
hospital group, which is composed of teaching hospitals, PCR) requiring antimicrobial therapy. A possible superinfection
including 2 main acute care facilities (Hôpital Raymond- was defined as a viral episode without bacterial documenta-
Poincaré and Hôpital Ambroise-Paré, with 255 and 399 tion, but for which antibiotic treatment was maintained beyond
beds, respectively) and a 55-bed geriatrics acute care facility 48 hours, based on clinical data and complementary results.
(Hôpital Sainte-Périne). Since November 2012, a remote in- A viral episode, or an excluded superinfection, was defined as a
fectious disease specialist consultant, working part time be- viral episode managed without antibiotics.
tween both hospitals, has been specifically devoted to promote The primary end point was the superinfection rate compar-
antibiotic stewardship. In addition an Anti-Infective Drug ison between influenza and paramyxovirus groups, including
Committee promotes good use of antimicrobials through ed- certain and possible superinfections. Secondary end points
ucational sessions for physicians and elaboration of antibiotic were the need for hospitalization and the occurrence of death,
administration protocols, based on local recommendations censored beyond day 90 after PCR testing.
that are available in a pocket guide for residents (also on the
intranet). The consultant also performs postprescription anti- Statistical Analysis
biotic review based on e-mail alerts generated on day 3 by the Outcomes and patient characteristics were compared according
pharmacist, leading to revaluation of broad-spectrum anti- to viruses. For purpose of analysis, PIV-1 and PIV-3 were gath-
biotics in particular. ered in order to increase the statistical strength. Descriptive
2 • JID 2021:XX (XX XX) • Lemarie et alstatistics are presented as numbers and percentages or means and 11 cases of influenza virus and paramyxovirus coinfection, and standard deviations, with skewed continuous data summar- we gathered a total of 590 cases (Figure 1). The mean (SD) pa- ized as medians and interquartile ranges. For quantitative and tient age was 71.0 (18.3) years, with a male-female sex ratio of qualitative variables, paired Student t tests were used to com- 0.91. The majority of patients were tested in the emergency pare 2 groups, and McNemar and Mann-Whitney-Wilcoxon department (79.2% [n = 467]), and the remaining tests were tests to compare >2 groups. performed in outpatient care (eg, consultation, hemodialysis, Factors associated with superinfection were identified using day hospital, 10.9% [n = 64]) or during hospitalization (10% multivariate logistic regression. Potential factors included were [n = 59]). sex, age, and factors that had a P value
Table 1. Patient Characteristics According to Type of Infection at Baseline
Patients, No. (%)
Characteristic Total Population (N = 590) Influenza Virus (n = 347) Paramyxovirus (n = 243) P Valuea
Age, mean (SD), y 71.0 (18.3) 69.61 (19.46) 72.88 (16.27) .03b
Male sex 281 (48) 174 (50) 107 (44) .17
Underlying respiratory disease 184 (31) 82 (24) 102 (42)LRTIs and superinfections, by virus species, is detailed in Admission
Figure 2. After first medical evaluation, patients were discharged (19.5%
Multivariate analysis (Table 2) revealed that superinfections [n = 115]), hospitalized (57.5% [n = 339]), or admitted to the
were not associated with the viral species (P = .33). Conversely, intensive care unit (23% [n = 135]) (Figure 1). Among hospi-
advanced age (P < .001), underlying respiratory disease talized patients, the mean (SD) length of stay was 9.4 (11.5)
(P = .004), neutrophil counts >7000/µL (P < .001), eosin- days for influenza infections, compared with 13.4 (14.5) days
ophil counts 0.25 ng/mL (P < .001) were factors independently asso- risk factors for hospitalization showed that paramyxovirus RTIs
ciated with superinfections. were at higher risk for hospitalization (P = .001) (Table 3). In
the same way that individuals with neutrophil counts >7000/µL
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
Treatment (P = .002) or with abnormal PCT values (P = .02) were at signif-
Among influenza-infected patients, 41% (n = 143) were treated icantly higher risk of superinfection and admission. However,
with oseltamivir, compared with 2.8% (n = 7) of those infected lymphopenia and eosinopenia were not predictors of hospital-
with paramyxovirus. Among superinfections (n = 332), the ization. While chronic respiratory disease was not associated
prescribed antibiotics included amoxicillin-clavulanate acid with hospital admission, long-term use of ICSs was (P = .02).
in 51% (n = 167), other injectable β-lactams in 25% (n = 80),
combination therapy (eg, a third-generation cephalosporin Outcomes
plus macrolide) in 13% (n = 41), and monotherapy in 11% Ultimately, death occurred for 52 patients (8.8%). After ex-
(amoxicillin in 4% [n = 14], macrolides in 3.7% [n = 12], and cluding 10 sudden deaths unrelated to RTI (eg, from metastatic
quinolones in 3.4% [n = 11]). The mean (standard deviation cancer), we observed 31 deaths (8.9%) in the influenza and 11
[SD]) duration of treatment was 7.03 (3.91) days. in paramyxovirus group (4.5%). Kaplan-Meier survival curves
Table 2. Potential Predictors of Superinfection
Univariate Model Multivariate Model
Variable OR (95% CI) P Valuea aOR (95% CI) P Valuea
b
Age >75 y 2.12 (1.47–3.10)Table 3. Potential Predictors of Hospitalization
Univariate Model Multivariate Model
a
Variable OR (95% CI) P Value aOR (95% CI) P Valuea
Age >75 y 2.79 (1.62–4.81.0 + Censored
0.8
Survival Probability, %
0.6
0.4
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
0.2
0.0
0 10 20 30 40 50 90
Time, d
Group Influenza Paramyxovirus
Figure 3. Kaplan-Meier survival curves by viral species during 90-day follow-up.
While our work highlighted a high proportion of Conversely, we observed that influenza-infected patients,
superinfections that could be disputed, we believe this is close although less often hospitalized, had significantly worse prog-
to real-life practice, often with widespread use of antibiotics noses (Figure 3). This result may seem surprising, given that
[23]. Nevertheless, the mean duration of treatment (7 days) was patients with influenza were younger and had fewer comorbid
shorter than the durations reported in the literature, about 10 conditions with the same rate of superinfections. One hypoth-
days for the same indication [24]. esis is that the intrinsic virulence of the influenza virus over-
Our univariate analysis also supports the favorable impact of comes the frailty of paramyxovirus-infected patients.
influenza vaccination in the prevention of superinfections, as al- Influenza is deemed to be a severe RTI, with a high burden of
ready reported [25], which could not be confirmed in the multivar- 650 000 deaths each year [27] requiring millions of vaccinations
iate analyses owing to several noninfluenza infections. Although every year around the world [28]. This supports the need to ex-
antipneumococcal vaccination is also recognized as effective for pand indications of influenza vaccination to collectively protect
such indications [26], it could not be studied in our cohort because patients at risk, as shown during the current vaccination cam-
of too many incomplete data. Of note, high CCIs and Fine scores paign against COVID-19 [29]. Therefore, we need to develop
were also found to be predictors of superinfection or admission new vaccines against other respiratory viruses, including RSV,
but were not selected in the multivariate models owing to a corre- which is in our study the second-deadliest virus, after influenza.
lation between other variables used in these scores. Likewise, pa- Nevertheless, our work has some limitations. First, owing to
tients with normal chest radiographic findings were not included the in-hospital setting of this study (with 80.5% of admissions),
in the analyses, as radiographic abnormalities were already a con- we could not extrapolate our findings to outpatients. Moreover,
founding factor for initiation of antimicrobial therapy. the retrospective nature of the study led to possible collection
Interestingly, predictors of superinfection share some simi- bias and may have reduced the power of some statistical asso-
larities with those associated with hospital admission. Indeed, ciations. However, because the majority of our cohort required
age >75 years, neutrophil count >7000/µL, and elevated PCT hospitalization, we were able to collect reliable data, reducing
level were found in both models. However, these variables this bias to a minimum. Second, superinfections were com-
should be analyzed in the light of clinical pictures to draw con- posed mainly of possible cases, with only a few categorized as
clusions. Indeed, use of ICSs appeared as a risk factor for ad- certain (n = 62 [23%]), owing to the lack of appropriate tools
mission, but chronic lung disease did not, possibly because the to confirm bacterial infections in real practice. Third, we also
use of ICSs reflect the impact of severity of obstructive lung regret that our study was able to focus on only a small panel of
disease. Interestingly, paramyxoviruses were associated with an 6 viruses. We thereby excluded other respiratory viruses of sig-
increased probability of admission. This could be explained by nificant weight, such as rhinoviruses or common coronaviruses,
the fact that the many individuals in this group had impaired which could have played a role and are now tested routinely in
general conditions (Table 1). our hospital group since the COVID-19 pandemic. Finally, our
Bacterial Superinfection Among Viruses • JID 2021:XX (XX XX) • 7study was not designed to identify risk factors for mortality, 3. Templeton KE, Scheltinga SA, van den Eeden WC,
which could be the subject of an ad hoc work based on the Graffelman AW, van den Broek PJ, Claas EC. Improved di-
subpopulation of hospitalized and superinfected individuals. agnosis of the etiology of community-acquired pneumonia
In conclusion, virus species does not appear to influence the with real-time polymerase chain reaction. Clin Infect Dis
risk of superinfection, for the 6 studied viruses. However, spe- 2005; 41:345–51.
cies does seem to influence the prognosis. Before the COVID- 4. Cawcutt K, Kalil AC. Pneumonia with bacterial and viral
19 pandemic, our study shows that influenza was among the coinfection. Curr Opin Crit Care 2017; 23:385–90.
most lethal respiratory viruses and pleads for the proper use 5. Ortiz JR, Neuzil KM, Rue TC, et al. Population-based inci-
of antiviral agents and large-scale vaccination. Further inves- dence estimates of influenza-associated respiratory failure
tigations are necessary to improve identification of patients at hospitalizations, 2003 to 2009. Am J Respir Crit Care Med
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
high risk superinfections, now that PCR tests are part of daily 2013; 188:710–5.
in-hospital practice, to limit the overuse of antibiotics. 6. Morens DM, Taubenberger JK, Fauci AS. Predominant role
of bacterial pneumonia as a cause of death in pandemic in-
Supplementary Data fluenza: implications for pandemic influenza preparedness.
Supplementary materials are available at The Journal of Infectious J Infect Dis 2008; 198:962–70.
Diseases online. Consisting of data provided by the authors to 7. Talbot TR, Poehling KA, Hartert TV, et al. Seasonality of
benefit the reader, the posted materials are not copyedited and invasive pneumococcal disease: temporal relation to docu-
are the sole responsibility of the authors, so questions or com- mented influenza and respiratory syncytial viral circula-
ments should be addressed to the corresponding author. tion. Am J Med 2005; 118:285–91.
8. Lee KH, Gordon A, Foxman B. The role of respiratory
Notes viruses in the etiology of bacterial pneumonia. Evol Med
Acknowledgments. The authors thank all their colleagues Public Heal 2016; 2016:95–109.
at Raymond-Poincare Teaching Hospital, especially Beatrice 9. Martin-Loeches I, van Someren Gréve F, Schultz MJ.
Touraine for her unfailing support. Bacterial pneumonia as an influenza complication. Curr
Author contributions. B. L., G. B., E. G., H. P., P. D. T., and Opin Infect Dis 2017; 30:201–7.
B. D. conceptualized and designed the manuscript, coordinated 10. Rynda-Apple A, Robinson KM, Alcorn JF. Influenza and
and supervised data collection, drafted the initial manuscript, bacterial superinfection: illuminating the immunologic
and reviewed the manuscript. B. L. and B. D. were in charge of mechanisms of disease. Infect Immun 2015; 83:3764–70.
the figure and the table. H. P., S. B., S. G., F. M., J. D., M. P., P. 11. Watson M, Gilmour R, Menzies R, Ferson M, McIntyre
D. T., and B. D. and reviewed and revised the manuscript. All P; New South Wales Pneumococcal Network. The asso-
authors approved the final manuscript as submitted and agree ciation of respiratory viruses, temperature, and other
to be accountable for all aspects of the work in ensuring that climatic parameters with the incidence of invasive pneu-
questions related to the accuracy or integrity of any part of the mococcal disease in Sydney, Australia. Clin Infect Dis
work are appropriately investigated and resolved. 2006; 42:211–5.
Potential conflicts of interest. P. D. T. has received consulting 12. Kim PE, Musher DM, Glezen WP, Rodriguez-Barradas MC,
fees or travel grants from ViiV Healthcare, MSD, and Gilead Nahm WK, Wright CE. Association of invasive pneumo-
Sciences. B. D. has received consulting fees or travel grants from coccal disease with season, atmospheric conditions, air pol-
ViiV Healthcare and Gilead Sciences. All other authors report lution, and the isolation of respiratory viruses. Clin Infect
no potentials conflict of interest. All authors have submitted the Dis 1996; 22:100–6.
ICMJE Form for Disclosure of Potential Conflicts of Interest. 13. Chen L, Han X, Li YL, Zhang C, Xing X. The clinical char-
Conflicts that the editors consider relevant to the content of the acteristics and outcomes of adult patients with pneumonia
manuscript have been disclosed. related to three paramyxoviruses. Front Med (Lausanne)
2021; 7:574128.
References 14. Papillard-Marechal S, Enouf V, Schnuriger A, et al.
1. Roth GA, Abate D, Abate KH, et al. Global, regional, and Monitoring epidemic viral respiratory infections using one-
national age-sex-specific mortality for 282 causes of death step real-time triplex RT-PCR targeting influenza A and B
in 195 countries and territories, 1980–2017: a system- viruses and respiratory syncytial virus. J Med Virol 2011;
atic analysis for the Global Burden of Disease Study 2017. 83:695–701.
Lancet 2018; 392:1736–88. 15. Bénézit F, Loubet P, Galtier F, et al; FLUVAC Study Group.
2. Welte T, Torres A, Nathwani D. Clinical and economic Non-influenza respiratory viruses in adult patients ad-
burden of community-acquired pneumonia among adults mitted with influenza-like illness: a 3-year prospective
in Europe. Thorax 2012; 67:71–9. multicenter study. Infection 2020; 48:489–95.
8 • JID 2021:XX (XX XX) • Lemarie et al16. Zhang Y, Wang Y, Zhao J, et al; CAP-China Network. 23. van Houten CB, Cohen A, Engelhard D, et al. Antibiotic
Severity and mortality of respiratory syncytial virus vs influ- misuse in respiratory tract infections in children and adults-a
enza A infection in hospitalized adults in China. Influenza prospective, multicentre study (TAILORED Treatment).
Other Respir Viruses 2020; 14:483–90. Eur J Clin Microbiol Infect Dis 2019; 38:505–14.
17. Équipe de surveillance de la grippe-Santé publique France. 24. Yi SH, Hatfield KM, Baggs J, et al. Duration of antibiotic use
Surveillance de la grippe en France métropolitaine, saison among adults with uncomplicated community-acquired
2015–2016. Bull Epidémiol Hebd 2016; 32-33:558–63. pneumonia requiring hospitalization in the United States.
18. Visseaux B, Burdet C, Voiriot G, et al. Prevalence of respira- Clin Infect Dis 2018; 66:1333–41.
tory viruses among adults, by season, age, respiratory tract 25. Choi A, Christopoulou I, Saelens X, García-Sastre A,
region and type of medical unit in Paris, France, from 2011 Schotsaert M. TIV vaccination modulates host responses to
Downloaded from https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab525/6390777 by guest on 26 November 2021
to 2016. PLoS One 2017; 12:e0180888. influenza virus infection that correlate with protection against
19. McCullers JA. Effect of antiviral treatment on the outcome bacterial superinfection. Vaccines (Basel) 2019; 7:113.
of secondary bacterial pneumonia after influenza. J Infect 26. Madhi SA, Klugman KP; Vaccine Trialist Group. A role for
Dis 2004; 190:519–26. Streptococcus pneumoniae in virus-associated pneumonia.
20. Klein EY, Monteforte B, Gupta A, et al. The frequency of Nat Med 2004; 10:811–3.
influenza and bacterial coinfection: a systematic review 27. World Health Organization. Up to 650 000 people die of
and meta-analysis. Influenza Other Respir Viruses 2016; respiratory diseases linked to seasonal flu each year. Saudi
10:394–403. Med J 2018; 39:109–10.
21. Lee N, Chan PK, Lui GC, et al. Complications and out- 28. European Centre for Disease Prevention and Control
comes of pandemic 2009 Influenza A (H1N1) virus infec- (ECDC). Seasonal influenza vaccination and antiviral use
tion in hospitalized adults: how do they differ from those in in EU/EEA member states. Stockholm, Swedcen: ECDC,
seasonal influenza? J Infect Dis 2011; 203:1739–47. 2018.
22. Falsey AR, Becker KL, Swinburne AJ, et al. Bacterial com- 29. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA
plications of respiratory tract viral illness: a comprehensive Covid-19 vaccine in a nationwide mass vaccination setting.
evaluation. J Infect Dis 2013; 208:432–41. N Engl J Med 2021; 384:1412–23.
Bacterial Superinfection Among Viruses • JID 2021:XX (XX XX) • 9You can also read
