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In this cross-sectional study, we studied performance of the International Severe Acute Respiratory and Emerging Infections Consortium mortality and deterioration scores in a cohort of 410 hospitalized patients (51.2% fully vaccinated). area under the receiver operating characteristic curves were 0.778 and 0.764, respectively, comparable to originally published validation cohorts. Subgroup analysis showed equally good performance in vaccinated and partially or unvaccinated patients.

Summary Background Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. Methods We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. Findings We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (46 [28%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Interpretation Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphasise the importance of public health and social measures in the ongoing pandemic outbreak response, and might have implications for longevity of immunity after vaccination. Funding National Medical Research Council, Biomedical Research Council, and A*STAR, Singapore.

Background:The risk of environmental contamination by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the intensive care unit (ICU) is unclear. We evaluated the extent of environmental contamination in the ICU and correlated this with patient and disease factors, including the impact of different ventilatory modalities.Methods:In this observational study, surface environmental samples collected from ICU patient rooms and common areas were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Select samples from the common area were tested by cell culture. Clinical data were collected and correlated to the presence of environmental contamination. Results were compared to historical data from a previous study in general wards.Results:In total, 200 samples from 20 patient rooms and 75 samples from common areas and the staff pantry were tested. The results showed that 14 rooms had at least 1 site contaminated, with an overall contamination rate of 14% (28 of 200 samples). Environmental contamination was not associated with day of illness, ventilatory mode, aerosol-generating procedures, or viral load. The frequency of environmental contamination was lower in the ICU than in general ward rooms. Eight samples from the common area were positive, though all were negative on cell culture.Conclusion:Environmental contamination in the ICU was lower than in the general wards. The use of mechanical ventilation or high-flow nasal oxygen was not associated with greater surface contamination, supporting their use and safety from an infection control perspective. Transmission risk via environmental surfaces in the ICUs is likely to be low. Nonetheless, infection control practices should be strictly reinforced, and transmission risk via droplet or airborne spread remains.

The complete picture regarding transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. This review summarises the available evidence on its transmission modes, our preliminary research findings and implications for infection control policy, and outlines future research directions. Environmental contamination has been reported in hospital settings occupied by infected patients, and is higher in the first week of illness. Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 ribonucleic acid in air samples, none has isolated viable virus in culture. Transmission likely lies on a spectrum between droplet and airborne transmission, depending on the patient, disease and environmental factors. Singapore’s current personal protective equipment and isolation protocols are sufficient to manage this risk.

SARS-CoV-2 variants of concern and vaccine escape, from Alpha to Omicron and beyond

BackgroundMultiple SARS-CoV-2 superspreading events suggest that aerosols play an important role in driving the COVID-19 pandemic. However, the detailed roles of coarse (>5μm) and fine (≤5μm) respiratory aerosols produced when breathing, talking, and singing are not well-understood.MethodsUsing a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing.ResultsAmong the 22 study participants, 13 (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic patients and 1 presymptomatic patient. Viral loads ranged from 63–5,821 N gene copies per expiratory activity per patient. Patients earlier in illness were more likely to emit detectable RNA, and loads differed significantly between breathing, talking, and singing. The largest proportion of SARS-CoV-2 RNA copies was emitted by singing (53%), followed by talking (41%) and breathing (6%). Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative.ConclusionsFine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in the transmission of SARS-CoV-2. Exposure to fine aerosols should be mitigated, especially in indoor environments where airborne transmission of SARS-CoV-2 is likely to occur. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging, and whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an important enquiry for future studies.Key PointsWe sampled respiratory aerosols emitted by COVID-19 patients and discovered that fine aerosols (≤5μm) generated during talking and singing contain more SARS-CoV-2 copies than coarse aerosols (>5μm) and may play a significant role in the transmission of SARS-CoV-2.

Objectives: Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. Methods: We conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. Results: Out of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015 e0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain. Discussion: The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic. National Medical Research Council (NMRC) Published version B.E.Y. reports personal fees from Roche, Sanofi and Gilead, outside the submitted work. All other authors declare no competing interests. This study was funded by grants from the Singapore National Medical Research Council (COVID19RF-001, COVID19RF-008). The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum β-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

A measles outbreak involving 19 adults in a home for the intellectually disabled occurred in Singapore in 2019. Further investigation, including a serological survey, was conducted. Mass vaccination and infection control measures were implemented, terminating further secondary transmission. Seropositivity among residents aged 40 to 49 years (90.7%; 95% confidence interval = 78.4%, 96.3%) was lower than among the Singapore adult population (P

Objectives: Predictive scores are important tools for the triage of patients with coronavirus disease 2019. The PRIORITY score is advantageous because it does not require laboratory and radiologic information. However, the original development and validation cohorts studied only unvaccinated patients in early 2020. We aimed to externally validate the PRIORITY score in a cohort of patients with the novel delta and omicron variants of coronavirus disease 2019 and mixed vaccination status. Methods: A total of 410 patients were included in a cross-sectional sampling of all patients admitted to the National Centre of Infectious Diseases on October 27, 2021. A further 102 and 136 patients with vaccine-breakthrough Delta and Omicron variant infection from April to August and December 2021, respectively, were also included. Variables at the time of admission were collected retrospectively from medical records and used to calculate the probability of deterioration using the PRIORITY model. Results: Of the total 648 included patients, 447 (69.0%) were vaccinated. The mean age was 61.6 years (standard deviation ± 19.0 years), and 268 patients (41.4%) were female. A total of 112 patients (17.3%) met the primary outcome of developing critical illness or mortality. The performance of the score in this cohort was comparable with the original cohorts, with an area under the receiver operating characteristic curve for all patients of 0.794 (95% CI, 0.752e0.835; p < 0.001), regression coefficient of 1.069, and intercept of 0.04. Subgroup analysis of unvaccinated and vaccinated patients showed that performance was superior in vaccinated individuals, with an area under the receiver operating characteristic curve of 0.684 (95% CI, 0.608e0.760; p < 0.0001) and 0.831 (95% CI, 0.772e0.891; p < 0.0001), respectively. Discussion: Our data support the continued use of the PRIORITY score in this era of novel variants and increased vaccination uptake. BEY reports personal fees from Roche and Sanofi outside of the submitted work. All other authors declare no competing interests. No additional funding was required for this study.

Highlights • In hospitalized older adults with COVID-19, geriatric syndromes are not uncommon. • Frailty and initial acuity are important predictors of COVID-19 disease severity. • CFS and FI are complementary in predicting disease progression in COVID-19., Introduction Older adults with COVID-19 have disproportionately higher rates of severe disease and mortality. It is unclear whether this is attributable to age or attendant age-associated risk factors. This retrospective cohort study aims to characterize hospitalized older adults and examine if comorbidities, frailty and acuity of clinical presentation exert an age-independent effect on COVID-19 severity. Methods We studied 275 patients admitted to the National Centre of Infectious Disease, Singapore. We measured: 1)Charlson Comorbidity Index(CCI) as burden of comorbidities; 2)Clinical Frailty Scale(CFS) and Frailty Index(FI); and 3)initial acuity. We studied characteristics and outcomes of critical illness, stratified by age groups (50–59,60–69 and ≥70). We conducted hierarchical logistic regression in primary model(N = 262, excluding direct admissions to intensive care unit) and sensitivity analysis(N = 275): age and gender in base model, entering CCI, frailty (CFS or FI) and initial acuity sequentially. Results The ≥70 age group had highest CCI(p

Background:Understanding the extent of aerosol-based transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for tailoring interventions for control of the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have reported the detection of SARS-CoV-2 nucleic acid in air samples, but only one study has successfully recovered viable virus, although it is limited by its small sample size.Objective:We aimed to determine the extent of shedding of viable SARS-CoV-2 in respiratory aerosols from COVID-19 patients.Methods:In this observational air sampling study, air samples from airborne-infection isolation rooms (AIIRs) and a community isolation facility (CIF) housing COVID-19 patients were collected using a water vapor condensation method into liquid collection media. Samples were tested for presence of SARS-CoV-2 nucleic acid using quantitative real-time polymerase chain reaction (qRT-PCR), and qRT-PCR-positive samples were tested for viability using viral culture.Results:Samples from 6 (50%) of the 12 sampling cycles in hospital rooms were positive for SARS-CoV-2 RNA, including aerosols ranging from 4 µm in diameter. Of 9 samples from the CIF, 1 was positive via qRT-PCR. Viral RNA concentrations ranged from 179 to 2,738 ORF1ab gene copies per cubic meter of air. Virus cultures were negative after 4 blind passages.Conclusion:Although SARS-CoV-2 is readily captured in aerosols, virus culture remains challenging despite optimized sampling methodologies to preserve virus viability. Further studies on aerosol-based transmission and control of SARS-CoV-2 are needed.

Introduction Chest radiographs (CXR) are widely used for the screening and management of the coronavirus disease 2019 (COVID-19). This paper determinates the radiographic features of COVID-19 based on an initial national cohort of patients. Methods This is a retrospective review of swab-positive COVID-19 patients admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXR were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities. Results In total, 347 CXR of 96 patients were reviewed. Initial CXR were abnormal in 41 out of 96 patients (42.7%). The mean time from onset of symptoms to CXR abnormality was 5.3 (range 1-21) days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXR (51.2%) and consolidation on follow-up CXR (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were seen in 63.4% and 59.2% of abnormal initial and follow-up CXR, respectively. The lower zones were involved in 90.2% of the initial CXR and 93.9% of the follow-up CXR. Conclusion In a cohort of swab-positive patients, including those identified from contact tracing, we found the incidence of CXR abnormality to be lower than previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

We report the clinical characteristics of two adult patients, presenting with a typical erythematous rash consistent with rubella disease after MMR vaccination. Both patients had an uncomplicated clinical course and recovered uneventfully. One patient was confirmed to have vaccine-associated rubella via sequencing of virus isolated in viral culture. The other patient had a pharyngeal swab positive for rubella virus PCR, with sequencing matching the vaccine strain. There are few reports of clinical disease from rubella vaccine-strains in the literature. Previous authors have reported severe disseminated vaccine-associated rubella in both immunodeficient and immunocompetent patients. Further study is required to ascertain the incidence, risk factors, and clinical characteristics of this condition; as well as investigate the extent of horizontal transmission to guide infection control recommendations.

Introduction: Two billion population are at risk of dengue fever and by 2080, over six billion population will be at risk. Hepatitis is common in dengue and the liver is invariably involved in severe cases. We conducted a literature review using the PubMed database on articles covering a broad range of issues related to dengue and hepatitis.Areas covered: This article overviews available literature on changes in the definition of severe dengue, pathogenesis of liver involvement in dengue, clinical manifestations, and predictors of mortality in severe dengue with liver involvement, impact of viral hepatitis co-infections and hepatotoxic drugs, and hemophagocytic lymphohistiocytosis.Expert commentary: Hepatitis is commonly seen in dengue however the degree of elevation of transaminases did not correlate well with severity of illness in observational studies, except in the elderly. The underlying pathogenesis of liver injury is still being elucidated and further studies are required to fully understand the cellular pathways. Acute or chronic viral hepatitis does not appear to affect dengue outcomes. Commonly used medications such as paracetamol and statins may influence dengue outcomes.

Objectives High-risk CXR features in COVID-19 are not clearly defined. We aimed to identify CXR features that correlate with severe COVID-19. Methods All confirmed COVID-19 patients admitted within the study period were screened. Those with suboptimal baseline CXR were excluded. CXRs were reviewed by three independent radiologists and opacities recorded according to zones and laterality. The primary endpoint was defined as hypoxia requiring supplemental oxygen, and CXR features were assessed for association with this endpoint to identify high-risk features. These features were then used to define criteria for a high-risk CXR, and clinical features and outcomes of patients with and without baseline high-risk CXR were compared using logistic regression analysis. Results 109 patients were included. In the initial analysis of 40 patients (36.7%) with abnormal baseline CXR, presence of bilateral opacities, multifocal opacities, or any upper or middle zone opacity were associated with supplemental oxygen requirement. Of the entire cohort, 29 patients (26.6%) had a baseline CXR with at least one of these features. Having a high-risk baseline CXR was significantly associated with requiring supplemental oxygen in univariate (odds ratio 14.0, 95% confidence interval 3.90–55.60) and multivariate (adjusted odds ratio 8.38, 95% CI 2.43–28.97, P = 0.001) analyses. Conclusion We identified several high-risk CXR features that are significantly associated with severe illness. The association of upper or middle zone opacities with severe illness has not been previously emphasized. Recognition of these specific high-risk CXR features is important to prioritize limited healthcare resources for sicker patients.