Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2.

Elena Mitsi,Jesús Reiné,Lisa Hitchins,Rohini Beavon,Konstantinos Liatsikos,Naomi F Walker,Simon J Draper,Bradford D Gessner,Daniela M Ferreira,Elissavet Nikolaou,Christian Theilacker,Britta C Urban,Ashleigh Howard,Katerina S Cheliotis,Esther L German,Carla Solórzano,Elizabeth Begier,Sherin Pojar,David Pulido,Madlen Farrar ,Emily Adams ,Ana I Cubas-Atienzar ,Christopher T Williams ,Sharon A Glynn ,Tom Fletcher ,Helen Hill ,Rachel L Byrne ,Angela Hyder-Wright ,Luis Jódar ,Andrea Collins

doi:10.1172/jci157124

Abstract

BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.MethodsHere, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.ResultsIn both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.ConclusionOur findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registrationISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).

Highlights

Despite the widespread global effects of the coronavirus disease 2019 (COVID-19) pandemic, few reports have assessed potential interactions between upper airway bacterial colonisation and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
A substantially low proportion of COVID-19 patients have documented pneumococcal pneumonia based on culture of blood or sputum samples collected during hospitalisation, with specimen collection often occurring after provision of antibiotics [1, 7, 9, 10] Bacterial and viral interaction in the upper airways could act synergistically to promote viral evasion by direct and indirect mechanisms [11, 12]
The impact of pneumococcal carriage on SARS-CoV-2 viral replication and clinical outcome was assessed in a cohort of frontline healthcare workers (HCW) (n=85, median age: 35; IQR: 27.5- 46.5) and a cohort of patients presented to hospital with suspected COVID-19 disease

Summary

Introduction

Despite the widespread global effects of the coronavirus disease 2019 (COVID-19) pandemic, few reports have assessed potential interactions between upper airway bacterial colonisation and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A recent observational study reported that 13-valent pneumococcal conjugate vaccine (PCV13) in older adults was associated with a reduction of approximately 30% in COVID-19 disease, hospitalisation, and death [6]. Recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of co-infection with Streptococcus pneumoniae in COVID-19 patients during hospitalisation have been reported infrequently. This apparent contradiction may be explained by interactions of SARS-CoV-2 and pneumococcus in the upper airway, resulting in the escape of SARSCoV-2 from protective host immune responses

Methods

Results

Conclusion