Neutrophils in respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, especially in infants. In clinical studies of RSV infection, neutrophils have long been implicated as drivers of disease severity as they make up the vast majority of the cellular composition of the airways of infants hospitalised with severe disease. Furthermore, a transcriptomic analysis found that genes related to neutrophil function were over-expressed in infants hospitalised with severe RSV infections. Although airway neutrophilia is a hallmark of severe RSV disease, the mechanisms underlying neutrophil recruitment and activation in the lung are not yet well understood. Furthermore, it is unclear whether airway neutrophilia during RSV infection contributes to viral control and/or drives disease severity. Mechanistic studies into the role of neutrophils during RSV infection in murine and bovine models of disease have suggested that neutrophils may release NETs in response to RSV but whether this causes lung pathology in a manner which affects the outcome of disease is unknown. In these studies, the innate immune signalling pathways underlying neutrophil recruitment and activation in RSV-infected mice were investigated. MyD88/TRIF signalling was found to be essential for lung neutrophil recruitment while MAVS signalling, leading to type I IFN production, was necessary for neutrophil activation. Furthermore, antibody mediated neutrophil depletion was used to investigate the role of neutrophils during RSV infection. Neutrophils were not required for the production type I interferons (IFNs) in response to RSV, nor did neutrophils contribute to viral control. Neutrophil depletion also demonstrated that neutrophil recruitment during primary RSV infection was not required for the formation of memory T cell responses during RSV re-challenge. Neither neutrophil removal nor the enhancement of airway neutrophilia, by administration of the chemoattractant CXCL1 following RSV infection, affected disease severity as measured by weight loss. However, increased airway neutrophilia pre-infection, as established by administration of CXCL1, enhanced disease severity as measured by weight loss during RSV infection. This was associated with an enhanced recruitment of CD8+ T cells to the lung at the peak of disease. This study found that two distinct pathogen sensing pathways must collaborate for neutrophil recruitment and activation during RSV infection. Furthermore, although neutrophil recruitment in response to RSV does not appear to drive disease in mice, pre-existing infections or conditions which heighten airway neutrophilia may contribute to disease severity during RSV infection.Open Acces

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 – 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 – 1.91) and 1.02 (0.93 – 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1.Conclusions: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low

Effects of COVID-19 Pandemic Response on Service Provision for Sexually Transmitted Infections, HIV, and Viral Hepatitis, England

Since the coronavirus disease pandemic response began in March 2020, tests, vaccinations, diagnoses, and treatment initiations for sexual health, HIV, and viral hepatitis in England have declined. The shift towards online and outreach services happened rapidly during 2020 and highlights the need to evaluate the effects of these strategies on health inequalities

Effectiveness of BNT162b2 and ChAdOx-1 vaccines in residents of long-term care facilities in England using a time-varying proportional hazards model

INTRODUCTION: residents of long-term care facilities (LTCFs) are at high risk of adverse outcomes from SARS-CoV-2. We aimed to estimate the vaccine effectiveness (VE) of one and two doses of BNT162b2 and ChAdOx-1 against SARS CoV-2 infection and COVID-19-related death in residents of LTCFs. METHODS: this observational study used testing, vaccination and mortality data for LTCF residents aged ≥ 65 years who were regularly tested regardless of symptoms from 8 December 2020 to 30 September 2021 in England. Adjusted VE, calculated as one minus adjusted hazard ratio, was estimated using time-varying Cox proportional hazards models for infection and death within 28 days of positive test result. Vaccine status was defined by receipt of one or two doses of vaccine and assessed over a range of intervals. RESULTS: of 197,885 LTCF residents, 47,087 (23.8%) had a positive test and 11,329 (5.8%) died within 28 days of a positive test during the study period. Relative to unvaccinated individuals, VE for infection was highest for ChAdOx-1 at 61% (40-74%) at 1-4 weeks and for BNT162b2 at 69% (52-80%) at 11-15 weeks following the second dose. Against death, VE was highest for ChAdOx-1 at 83% (58-94%) at 1-4 weeks and for BNT162b2 at 91% (75-97%) at 11-15 weeks following second dose. CONCLUSIONS: compared with unvaccinated residents, vaccination with one dose of BNT162b2 or ChAdOx-1 provided moderate protection against infection and death in residents of LTCFs. Protection against death improved after two doses. However, some waning of protection over time was noted

Association between COVID-19 Vaccination and SARS-CoV-2 Infection among Household Contacts of Infected Individuals: A Prospective Household Study in England

Background: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. Methods: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts’ vaccination status as the main exposure while adjusting for confounders. Results: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35–0.72) and 0.69 (0.53–0.90) for receipt of two doses 8–90 and >90 days ago, respectively, and 0.34 (0.23–0.50) for vaccination with three doses 8–151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts’ infection risk: 0.45 (0.23–0.89). Conclusions: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose