Non-pharmaceutical interventions and risk of COVID-19 infection: survey of U.K. public from November 2020 - May 2021.

INTRODUCTION: Non-pharmaceutical interventions (NPIs), such as handwashing, social distancing and face mask wearing, have been widely promoted to reduce the spread of COVID-19. This study aimed to explore the relationship between self-reported use of NPIs and COVID-19 infection. METHODS: We conducted an online questionnaire study recruiting members of the UK public from November 2020 to May 2021. The association between self-reported COVID-19 illness and reported use of NPIs was explored using logistic regression and controlling for participant characteristics, month of questionnaire completion, and vaccine status. Participants who had been exposed to COVID-19 in their household in the previous 2 weeks were excluded. RESULTS: Twenty-seven thousand seven hundred fifty-eight participants were included and 2,814 (10.1%) reported having a COVID-19 infection. The odds of COVID-19 infection were reduced with use of a face covering in unadjusted (OR 0.17 (95% CI: 0.15 to 0.20) and adjusted (aOR 0.19, 95% CI 0.16 to 0.23) analyses. Social distancing (OR 0.27, 95% CI: 0.22 to 0.31; aOR 0.35, 95% CI 0.28 to 0.43) and handwashing when arriving home (OR 0.57, 95% CI 0.46 to 0.73; aOR 0.63, 95% CI: 0.48 to 0.83) also reduced the odds of COVID-19. Being in crowded places of 10-100 people (OR 1.89, 95% CI: 1.70 to 2.11; aOR 1.62, 95% CI: 1.42 to 1.85) and > 100 people (OR 2.33, 95% CI: 2.11 to 2.58; aOR 1.73, 95% CI: 1.53 to 1.97) were both associated with increased odds of COVID-19 infection. Handwashing before eating, avoiding touching the face, and cleaning things with virus on were all associated with increased odds of COVID-19 infections. CONCLUSIONS: This large observational study found evidence for strong protective effects for individuals from use of face coverings, social distancing (including avoiding crowded places) and handwashing on arriving home on developing COVID-19 infection. We also found evidence for an increased risk associated with other behaviours, possibly from recall bias.

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.

BACKGROUND: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. METHODS: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older-or aged 18 years or older with relevant comorbidities-and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81-1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. INTERPRETATION: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. FUNDING: UK National Institute for Health and Care Research.

Self-sampling to identify pathogens and inflammatory markers in patients with acute sore throat: Feasibility study.

Introduction: Sore throat is a common reason for overuse of antibiotics. The value of inflammatory or biomarkers in throat swab or saliva samples in predicting benefit from antibiotics is unknown. Methods: We used the 'person-based approach' to develop an online tool to support self-swabbing and recruited adults and children with sore throats through participating general practices and social media. Participants took bacterial and viral swabs and a saliva sponge swab and passive drool sample. Bacterial swabs were cultured for streptococcus (Group A, B, C, F and G). The viral swab and saliva samples were tested using a routine respiratory panel PCR and Covid-19 PCR testing. We used remaining viral swab and saliva sample volume for biomarker analysis using a panel of 13 biomarkers. Results: We recruited 11 asymptomatic participants and 45 symptomatic participants. From 45 symptomatic participants, bacterial throat swab, viral throat swab, saliva sponge and saliva drool samples were returned by 41/45 (91.1%), 43/45 (95.6%), 43/45 (95.6%) and 43/45 (95.6%) participants respectively. Three saliva sponge and 6 saliva drool samples were of insufficient quantity. Two adult participants had positive bacterial swabs. Six participants had a virus detected from at least one sample (swab or saliva). All of the biomarkers assessed were detectable from all samples where there was sufficient volume for testing. For most biomarkers we found higher concentrations in the saliva samples. Due to low numbers, we were not able to compare biomarker concentrations in those who did and did not have a bacterial pathogen detected. We found no evidence of a difference between biomarker concentrations between the symptomatic and asymptomatic participants but the distributions were wide. Conclusions: We have demonstrated that it is feasible for patients with sore throat to self-swab and provide saliva samples for pathogen and biomarker analysis. Typical bacterial and viral pathogens were detected but at low prevalence rates. Further work is needed to determine if measuring biomarkers using oropharyngeal samples can help to differentiate between viral and bacterial pathogens in patients classified as medium or high risk using clinical scores, in order to better guide antibiotic prescribing and reduce inappropriate prescriptions.

Understanding GPs' views and experiences of using clinical prediction rules in the management of respiratory infections: a qualitative study.

BACKGROUND: Respiratory tract infections (RTIs) account for 60% of antibiotic prescribing in primary care. Several clinical prediction rules (CPRs) have been developed to help reduce unnecessary prescribing for RTIs, but there is a lack of studies exploring whether or how these CPRs are being used in UK general practice. AIM: To explore UK GPs' views and experiences with regards to RTI CPRs, and to identify barriers and facilitators to their use in practice. DESIGN & SETTING: A qualitative analysis of interviews with in-hours GPs working in the South and South West of England. METHOD: Semi-structured qualitative telephone interviews were conducted, digitally recorded, transcribed verbatim, and analysed using an inductive thematic approach. Patient and public involvement representatives contributed to study design and interpretation of findings. RESULTS: Thirty-two GPs were interviewed. Some CPRs were more commonly used than others. Participants used CPRs to facilitate patient-clinician discussion, confirm and support their decision, and document the consultation. GPs also highlighted concerns including lack of time, inability of CPRs to incorporate patient complexity, a shift in focus from the patient during consultations, and limited use in remote consultation (during the COVID-19 pandemic). CONCLUSION: This study highlights the need for user-friendly CPRs that are readily integrated into computer systems, and easily embedded into routine practice to complement clinical decision-making. Existing CPRs need to be validated for other populations where demographics and clinical characteristics may differ, as well different settings including remote consultations and self-assessment.