Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Utility of ISARIC 4C Mortality Score, Vaccination History, and Anti-S Antibody Titre in Predicting Risk of Severe COVID-19.

The ISARIC 4C Mortality score was developed to predict mortality risk among patients with COVID-19. Its performance among vaccinated individuals is understudied. This is a retrospective study of all patients with SARS-CoV-2 infection admitted to the National Centre for Infectious Diseases, Singapore, from January-2020 to December-2021. Demographic, clinical, and laboratory data were extracted, and multiple logistic regression (MLR) models were developed to predict the relationship between ISARIC score, vaccination status, anti-S antibody titre, and severe COVID-19. A total of 6377 patients were identified, of which 5329 met the study eligibility criteria. The median age of the patients was 47 years (IQR 35-71), 1264 (23.7%) were female, and 1239 (25.7%) were vaccinated. Severe disease occurred in 499 (9.4%) patients, including 133 (2.5%) deaths. After stratification, 3.0% of patients with low (0-4), 17.8% of patients with moderate (5-9), and 36.2% of patients with high (≥10) ISARIC scores developed severe COVID-19. Vaccination was associated with a reduced risk of progression to severe COVID-19 in the MLR model: aOR 0.88 (95% CI: 0.86-0.90), and the risk of severe COVID-19 decreased inversely to anti-S antibody titres. The anti-S antibody titre should be further investigated as an adjunct to the ISARIC score to triage COVID-19 patients for hospital admission and antiviral therapy.

The Omicron-transformer: Rise of the subvariants in the age of vaccines.

INTRODUCTION: Omicron is the latest SARS-CoV-2 variant of concern, the pathogen that causes COVID-19. Since its emergence in late 2021, Omicron has displaced other circulating variants and caused successive waves of infection worldwide throughout 2022. Omicron is characterised by the rapid emergence of many subvariants and high rates of infection in people with vaccine- and/or infection induced immunity. This review article will consolidate current knowledge regarding Omicron subvariants, the role of boosters, and future vaccine development. METHOD: This narrative review is based on a literature search using PubMed. Search terms related to Omicron were used and priority was given to published peer-reviewed articles over pre-prints. RESULTS: Studies indicate that vaccinations and boosters are important to reduce disease severity, hospitalisation, and death from Omicron. A variety of factors, such as differing host factors, circulating variants, and forces of infection, can influence the benefit of repeated booster administration. Next-generation bivalent vaccines have now been approved in some countries including Singapore and have demonstrated the ability to induce broad variant protection. Future third-generation vaccines involving mucosal vaccines and/or pan-sarbecovirus vaccines may provide broader and longer-lasting protection. CONCLUSION: Due to current high levels of vaccine- and infection-induced immunity, it is likely that rates of severe illness, hospitalisation, and death due to Omicron will continue to moderate. Nevertheless, the virus is ever-changing, and public health policies, especially those related to vaccinations, will also have to continually evolve and adapt as COVID-19 transitions to endemicity.