Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus

Abstract

Background: A mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP).

Methods: A retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics.

Results: Compared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)].

Conclusions: The prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.

Keywords: COVID-19; Co-infection; Influenza; Respiratory syncytial virus; SARS-CoV-2.

Fig. 1

Bacterial co-infection testing frequency and positivity rate per virus group and diagnostic test modality. For testing frequency, the proportion represents the number of patients having each test performed at admission divided by the total number of patients per virus group. The number of tested individuals are found within brackets. For positivity rate, the proportion represents the number of patients with a positive test per test modalitiy divided by the total number of tested patients per virus group. The number of positive individuals are found within brackets. RSV, respiratory syncytial virus; SARS-COV-2,severe acute respiratory syndrome coronavirus 2; NPH, nasopharyngeal; LRT, lower respiratory tract

Fig. 2

Bacterial co-infection etiologies in SARS-CoV-2, influenza and RSV. Bacterial etiologies in SARS-CoV-2 (upper), influenza (middle) and RSV (lower). The proportion represents the proportion of all patients tested positive per virus category (SARS-CoV-2 = 46, Influenza = 209, RSV = 69). RSV, respiratory syncytial virus; SARS-COV-2,severe acute respiratory syndrome coronavirus 2, spp, species