Real-world effectiveness of sotrovimab and remdesivir for early treatment of high-risk hospitalized COVID-19 patients: A propensity score adjusted retrospective cohort study.

Early treatment of high-risk COVID-19 patients may prevent disease progression. However, there are limited data to support treatment of hospitalized or fully vaccinated patients with mild-to-moderate disease. In this retrospective cohort study, we studied the effect of early use of sotrovimab and remdesivir in high-risk hospitalized COVID-19 patients. We included PCR-confirmed COVID-19 patients admitted to the National Centre for Infectious Diseases who presented within the first 5 days of illness, and who were not requiring oxygen or ICU care at presentation. Sotrovimab- and remdesivir-treated groups were compared with control (no early treatment). A multiple propensity-score adjusted multivariable regression analysis was conducted with a composite primary endpoint of in-hospital deterioration (oxygen requirement, ICU admission, or mortality). Of 1118 patients, 841 were in the control group, 106 in the sotrovimab group and 169 in the remdesivir group. The median age was 63 years (IQR 46-74 years) and 505 (45.2%) were female. In unvaccinated patients, both remdesivir and sotrovimab treatment were protective (adjusted odds ratio [aOR] 0.19, 95% CI 0.064-0.60 and 0.18 [95% CI 0.066-0.47]), respectively. Contrarily, among the vaccinated patients there was no significant treatment effect with early remdesivir treatment (aOR 2.51, 95% CI 0.83-7.57, p = 0.10). Remdesivir and sotrovimab treatment, given early in the disease course to unvaccinated high-risk patients, was effective in reducing the risk of in-hospital deterioration and severe disease. This effect was not seen in fully vaccinated patients, which may be due to a small sample size or residual confounding.

Healthcare workers in Singapore infected with COVID-19: 23 January-17 April 2020.

OBJECTIVE: To describe the characteristics of healthcare workers (HCWs) infected with COVID-19 and to examine their sources of exposure. METHODS: A descriptive cross-sectional study using data extracted from the centralized disease notification system comprising individuals confirmed with COVID-19 in Singapore between 23 January and 17 April 2020. Occupation of HCWs was categorized into six categories. Their job nature was classified into "frontline" or "back-end" based on the frequency of direct patient contact, and source of exposure was classified as family/household, social interaction or workplace. Chi-square and median tests were used to identify differences between categorical groups and sample medians, respectively. RESULTS: A total of 88 (1.7%) HCWs were identified from 5,050 cases. Their median age was 35 years. Chinese and Indians constituted 42.0% and 31.8%, respectively, and 43.2% were foreigners. The majority (63.6%) was serving at frontlines handling patient-facing duties, 15.9% were doctors, 11.4% were nurses and 44.3% were ancillary staff. About 81.8% acquired the infection locally, of which 40.3% did not have a clearly identifiable source of exposure. Exposure from the family/household was most common (27.8%), followed by workplace (16.7%) and social interaction (15.3%). All HCWs were discharged well with no mortality; three (3.4%) were ever admitted to intensive care unit and required increased care. CONCLUSION: Healthcare workers accounted for a small proportion of COVID-19 cases in Singapore with favourable outcomes. The possibility of transmission resulting from family/household exposure and social interactions highlights the need to maintain strict vigilance and precautionary measures at all times beyond the workplace.

Connecting clusters of COVID-19: an epidemiological and serological investigation.

BACKGROUND: Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. METHODS: In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. FINDINGS: Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. INTERPRETATION: Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. FUNDING: National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).