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

Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, secondary pneumococcal pneumonia has been reported as infrequent. This apparent contradiction may be explained by interactions of SARS-CoV-2 and pneumococcus in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses. Here, we investigated the relationship of these two respiratory pathogens in two distinct cohorts of a) healthcare workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and b) patients with moderate to severe disease who presented to hospital. We assessed the effect of co-infection on host antibody, cellular and inflammatory responses to the virus. In both cohorts, pneumococcal colonisation was associated with diminished anti-viral immune responses, which affected primarily mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients. Our findings suggest that S. pneumoniae modulates host immunity to SARS-CoV-2 and raises the question if pneumococcal carriage also enables immune escape of other respiratory viruses through a similar mechanism and facilitates reinfection occurrence.

Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: an observational cohort study.

BackgroundThe SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the UK National Health Service (NHS). During the first wave of SARS-CoV-2 transmission in UK, SARS-CoV-2 NHS diagnostic test availability was limited to self-isolating symptomatic staff. The burden of symptomatic and asymptomatic infection in healthcare workers (HCW) attending work was unknown. MethodsWe conducted an observational cohort study of SARS-CoV-2 infection in HCW working in an acute NHS Trust during the first wave of the COVID-19 pandemic, using serial self-collected saliva and nasopharyngeal (NP) samples. We also collected self-assessed symptom profiles and isolation behaviours. We retrospectively compared SARS-CoV-2 detection by RT-PCR from saliva (weekly) and NP swabs (twice weekly) from 85 individuals in this cohort and evaluated the association with symptoms. FindingsOver a 12-week period from 30th March 2020, 40% (n=34/85, CI95% 31.3-51.8%) HCWs had evidence of SARS-CoV-2 infection by surveillance NP swab and/or saliva RT-qPCR. Agreement between paired saliva and NP swabs was poor (28.6%, CI95% 13.2-48.7%) with both methods detecting symptomatic and asymptomatic infections. Symptoms were reported by 47.1% (n=40) and self-isolation by 25.9% participants (n=22). Only 41.2% (n=14/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of the infection. InterpretationHCWs are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections in HCW. Saliva is an easily accessible fluid sample for screening for SARS-CoV-2 infection and in addition to NP swab, facilitated ascertainment of symptomatic and asymptomatic cases in this setting. Combined saliva and NP testing would improve detection of SARS-CoV-2 for surveillance. Better understanding of transmissibility from asymptomatic staff using transmission-based infection precautions, is required to inform policy.

Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2

BackgroundReliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection and ease-of-use of three antigen-detecting, rapid POC tests (Ag-RDT) for SARS-CoV-2. MethodsThis prospective, multi-centre diagnostic accuracy study recruited participants suspected to have SARS-CoV-2 in Germany and the UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical RT-PCR and one for Ag-RDT). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptoms onset, etc. In addition, limited verification of the analytical limit-of-detection (LOD) was determined. To understand the usability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. ResultsBetween April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76x6% (95% Confidence Interval (CI) 62x8-86x4) sensitive and 99x3% (CI 98x6-99x6) specific. A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC. Bioeasy and Coris showed specificity of 93x1% (CI 91x0%-94x8%) and 95x8% (CI 93x4%-97x4%), respectively, not meeting the predefined target of [≥]98%. ConclusionThere is large variability in performance of Ag-RDT with SD Biosensor showing promise. Given the usability at POC, this test is likely to have impact despite imperfect sensitivity; however further research and modelling are needed.

Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.

RT-qPCR utilising upper respiratory swabs are the diagnostic gold standard for SARS-CoV-2 despite reported low sensitivity and limited scale up due to global shortages. Saliva is a non-invasive, equipment independent alternative to swabs. We collected 145 paired saliva and nasal/throat (NT) swabs at diagnosis (day 0) and repeated on day 2 and day 7 dependent on inpatient care and day 28 for study follow up. Laboratory cultured virus was used to determine the analytical sensitivity of spiked saliva and swabs containing amies preservation media. Self-collected saliva samples were found to be consistent, and in some cases superior when compared to healthcare worker collected NT swabs from COVID-19 suspected participants. We report for the first time the analytical limit of detection of 10-2and 100 pfu/ml for saliva and swabs respectively. Saliva is a easily self-collected, highly sensitive specimen for the detection of SARS-CoV-2.