Results from a systematic programme of evaluating COVID-19 reinfection cases in the early phase of the pandemic, Singapore.

OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.

Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis.

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor.

Identifying COVID-19 cases in outpatient settings.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study.

PURPOSE: To investigate the prevalence and epidemiological risk factors of olfactory and/or taste disorder (OTD), in particular isolated OTD, in patients with laboratory-confirmed COVID-19 infection. METHODS: We conducted a retrospective and cross-sectional study. Patients with laboratory-confirmed COVID-19 infection were recruited from the National Centre for Infectious Diseases (NCID) Singapore between 24 March 2020 and 16 April 2020. The electronic health records of these patients were accessed, and demographic data and symptoms reported (respiratory, self-reported OTD and other symptoms such as headache, myalgia and lethargy) were collected. RESULTS: A total of 1065 patients with laboratory-confirmed COVID-19 were recruited. Overall, the prevalence of OTD was 12.6%. Twelve patients (1.1%) had isolated OTD. The top three symptoms associated with OTD were cough, fever and sore throat. The symptoms of runny nose and blocked nose were experienced by only 29.8 and 19.3% of patients, respectively. Multivariate analysis demonstrated that the female gender, presence of blocked nose and absence of fever were significantly associated with OTD (adjusted relative risks 1.77, 3.31, 0.42, respectively). All these factors were statistically significant. CONCLUSION: Patients with COVID-19 infection can present with OTD, either in isolation or in combination with other general symptoms. Certain demographic profile, such as being female, and symptomatology such as the presence of blocked nose and absence of fever, were more likely to have OTD when infected by COVID-19. Further studies to elucidate the pathophysiology of OTD in these patients will be beneficial.

Acute Onset of Bilateral Follicular Conjunctivitis in two Patients with Confirmed SARS-CoV-2 Infections.

PURPOSE: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. PARTICIPANTS AND METHODS: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were examined. Conjunctival swabs were assessed for the presence of SARS-CoV-2 by quantitative real-time polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Both patients developed eye redness 3 days after the onset of COVID-19 symptoms. Slit lamp examination showed bilateral acute follicular conjunctivitis, which was resolved within 6 days. RT-PCR demonstrated the presence of viral RNA in conjunctival specimens from both eyes, which was unrelated to viral RNA from throat swabs. CONCLUSION: SARS-CoV-2 may cause ocular manifestations such as viral conjunctivitis. Conjunctival sampling may be useful for infected patients with conjunctivitis and fever. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection.

Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.

The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.

Correlation of clinical illness with viremia in Zika virus disease during an outbreak in Singapore.

BACKGROUND: The first autochthonous Zika virus (ZIKV) outbreak in Singapore was detected in August 2016. We report an analysis of the correlation of clinical illness with viremia and laboratory parameters in this Asian cohort. METHODS: We conducted a prospective longitudinal cohort study of patients with a positive blood ZIKV polymerase chain reaction (PCR) result who were admitted to Tan Tock Seng Hospital, Singapore, for isolation and management. RESULTS: We included 40 patients in our study. Rash was present in all patients, while 80% (32/40) had fever, 62.5% (25/40) myalgia, 60% (24/40) conjunctivitis and 38% (15/40) arthralgia. The median duration of viremia was 3.5 days (IQR: 3-5 days). Patients with viremia of ≥4 days were more likely to have prolonged fever compared to those with viremia of less than 4 days (95% versus 63%, p = 0.01), but had no significant correlation with other clinical signs and symptoms, or laboratory investigations. However, 21 patients (53%) had hypokalemia despite the absence of gastrointestinal symptoms. CONCLUSION: Although fever correlated with duration of viremia, 30% of patients remained viremic despite defervescence. Laboratory abnormalities such as leukopenia or thrombocytopenia were not prominent in this cohort but about half the patients were noted to have hypokalemia.

Cost Effectiveness of Universal Hepatitis B Virus Screening in Patients Beginning Chemotherapy for Sarcomas or GI Stromal Tumors.

PURPOSE: The value of screening for hepatitis B virus (HBV) infection before chemotherapy for nonhematopoietic solid tumors remains unsettled. We evaluated the cost effectiveness of universal screening before systemic therapy for sarcomas, including GI stromal tumors (GISTs). PATIENTS AND METHODS: Drawing from the National Cancer Centre Singapore database of 1,039 patients with sarcomas, we analyzed the clinical records of 485 patients who received systemic therapy. Using a Markov model, we compared the cost effectiveness of a screen-all versus screen-none strategy in this population. RESULTS: A total of 237 patients were screened for HBV infection. No patients developed HBV reactivation during chemotherapy. The incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) of offering HBV screening to all patients with sarcomas and patients with GISTs exceeded the cost-effectiveness threshold of SG$100,000 per QALY. This result was robust in one-way sensitivity analysis. Our results show that only changes in mortality rate secondary to HBV reactivation could make the incremental cost-effectiveness ratio cross the cost-effectiveness threshold. CONCLUSION: Universal HBV screening in patients with sarcomas or GISTs undergoing chemotherapy is not cost effective at a willingness to pay of SG$100,000 per QALY and may not be required.

Neurophobia in medical students and junior doctors--blame the GIK.

INTRODUCTION: We aimed to create a definition of neurophobia, and determine its prevalence and educational risk factors amongst medical students and junior doctors in Singapore. MATERIALS AND METHODS: We surveyed medical students and junior doctors in a general hospital using electronic and paper questionnaires. We asked about knowledge, interest, perceived difficulty in neurology, and confidence in managing neurology patients compared to 7 other internal medicine specialties; quality and quantity of undergraduate and postgraduate neuroscience teaching, clinical neurology exposure, and postgraduate qualifications. Neurophobia was defined as ≤4 composite score of difficulty and confidence with neurology. RESULTS: One hundred and fifty-eight medical students (63.5%) and 131 junior doctors (73.2%) responded to the questionnaire. Neurophobia prevalence was 47.5% in medical students, highest amongst all medical subspecialties, and 36.6% in junior doctors. Multivariate analysis revealed that for medical students, female gender (OR 3.0, 95% CI, 1.3 to 6.7), low interest (OR 2.5, 95% CI, 1.0 to 6.2), low knowledge (OR 10.1, 95% CI, 4.5 to 22.8), and lack of clinical teaching by a neurologist (OR 2.8, 95% CI, 1.2 to 6.6) independently increased the risk of neurophobia. For doctors, low interest (OR 3.0, 95% CI, 1.3 to 7.0) and low knowledge (OR 2.7, 95% CI, 1.2 to 6.2) independently increased the risk of neurophobia, and female gender was of borderline significance (OR 2.0, 95% CI, 0.9 to 4.6). CONCLUSION: Neurophobia is highly prevalent amongst Singapore medical students and junior doctors. Low interest and knowledge are independent risk factors shared by both groups; female gender may also be a shared risk factor. The mnemonic GIK (Gender, Interest, Knowledge) identifies the risk factors to mitigate when planning teaching strategies to reduce neurophobia.