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Summary Background Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. Methods We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. Findings As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. Interpretation SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. Funding None.

Highlights • Peripheral blood leucocyte ratios are useful infection biomarkers. • Neutrophil:lymphocyte ratio (NLR) is predictive of bacteraemia. • NLR should be included in future stratification models to identify sepsis endotypes. • Lymphocyte:monocyte ratio is predictive of influenza virus infection. • Utility was also found in CAP, UTI, pertussis, CCHF and diabetic foot infections., Summary Objectives To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers. Methods PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032. Results Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality. Conclusions Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24–6.47) and neutrophil count (aOR 2.39, 95% CI 1.34–4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828–0.979). Median APACHE II score was 19 (IQR 17–22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89–129). Median peak FiO2 was 0.75 (IQR 0.6–1.0), positive end-expiratory pressure 12 (IQR 10–14) and plateau pressure 22 (IQR 18–26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5–13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.

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.

Objectives To determine whether the frequencies of SARS‐CoV‐2‐specific T cells are sufficiently high in the blood of convalescent donors and whether it is technically feasible to manufacture clinical‐grade products overnight for T‐cell therapy and assessment of COVID‐19 immunity. Methods One unit of whole blood or leukapheresis was collected from each donor following standard blood bank practices. The leukocytes were stimulated using overlapping peptides of SARS‐CoV‐2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereafter, functionally reactive cells were enriched overnight using an automated device capturing IFNγ‐secreting cells. Results From 1 × 109 leukocytes, a median of 0.98 × 106 (range 0.56‐2.95) IFNγ + T cells were produced from each of the six donors, suggesting a high frequency of SARS‐CoV‐2 reactive T cells in their blood, even though only one donor had severe COVID‐19 requiring mechanical ventilation whereas the other five donors had minor symptoms. A median of 57% of the enriched T cells were IFNγ+ (range 20%‐74%), with preferential enrichment of CD56+ T cells and effector memory T cells. TCRVβ‐spectratyping confirmed distinctively tall oligoclonal peaks in final products. With just six donors, the probability that a recipient would share at least one HLA allele with one of the donors is >88% among Caucasian, >95% among Chinese, >97% among Malay, and >99% among Indian populations. Conclusions High frequencies of rapid antigen‐reactive T cells were found in convalescent donors, regardless of severity of COVID‐19. The feasibility of clinical‐grade production of SARS‐CoV‐2‐specific T cells overnight for therapeutics and diagnostics is revealed.

Background Dengue fever usually presents as a self-limiting acute febrile illness with worsening thrombocytopenia, with a small minority of patients developing hemorrhagic or life-threatening complications. Organ specific manifestations like myocarditis, acalculous cholecystitis, encephalitis has been described but are uncommon presentations. Even more rarely, such manifestations are the presenting complaint of Dengue fever. In this case report, we highlight a case of Dengue fever where unrelated neuropathies were the presenting complaint. Case presentation An elderly man presents with 1 day of diplopia and left foot drop, associated with 2 days history of fever. A decreasing white cell count (WBC) and platelet on the 2nd day of admission prompted Dengue virus to be tested and a positive NS-1 antigen was detected, confirming the diagnosis of Dengue fever. He was treated with supportive treatment with a short duration of intravenous fluids recovered uneventfully and was discharged 6 days after admission with almost full resolution of diplopia and partial resolution of left foot drop. Left foot drop recovered completely 2 weeks later. Conclusion Neurological manifestations can be the presenting symptoms in Dengue fever, a diagnosis which should be borne in mind when such symptoms present in patients from endemic areas or in returning travellers from these areas.

SUMMARYBackgroundAdoptive therapy with SARS-CoV-2 specific T cells for COVID-19 has not been reported. The feasibility of rapid clinical-grade manufacturing of virus-specific T cells from convalescent donors has not been demonstrated for this or prior pandemics.MethodsOne unit of whole blood was collected from each convalescent donor following standard blood bank practices. After the plasma was separated and stored separately, the leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereaftesr, functionally reactive cells were enriched overnight using an automated device capturing IFNγ-secreting cells.FindingsFrom 1×109 leukocytes, 0.56 to 1.16×106 IFNγ+ T cells were produced from each of the first two donors. Most of the T cells (64% to 71%) were IFNγ+, with preferential enrichment of CD56+ T cells, effector memory T cells, and effector memory RA+ T cells. TCRVβ spectratyping revealed oligoclonal distribution, with over-representation of subfamilies including Vβ3, Vβ16 and Vβ17. With just two donors, the probability that a recipient in the same ethnic group would share at least one donor HLA allele or one haplotype could be as high as >90% and >30%, respectively.InterpretationsThis study is limited by small number of donors and absence of recipient data; however, crucial first proof-of-principle data are provided demonstrating the feasibility of clinical-grade production of SARS-CoV-2 specific T cells for urgent clinical use, conceivably with plasma therapy concurrently. Our data showing that virus-specific T cells can be detected easily after brief stimulation with SARS-CoV-2 specific peptides suggest that a parallel diagnostic assay can be developed alongside serology testing.FundingThe study was funded by a SingHealth Duke-NUS Academic Medicine COVID-19 Rapid Response Research Grant.

Background To determine the utility of chest radiography (CXR) for assessing and prognosticating COVID-19 disease with an objective radiographic scoring system.Methods A multicenter, prospective study was conducted, forty patients were included. Seventy-eight CXR’s were performed on the first derivation cohort of twenty patients with COVID-19 (median age 47.5 years, 10 females and four with comorbidities) admitted between 22 January 2020 and 1 February 2020. Each CXR was scored by three radiologists in consensus and graded on a 72-point COVID-19 Radiographic Score (CRS). This was correlated with supplemental oxygen requirement, C-reactive protein (CRP), lactate dehydrogenase (LDH) and lymphocyte count. To validate our findings, the parameters of another validation cohort of twenty patients with 65 CXRs were analysed.Results In the derivation cohort, seven patients needed supplemental oxygen and one was intubated for mechanical ventilation with no death. The maximum CRS was significantly different between patients on and not on supplemental oxygen (p=Conclusion Using an objective scoring system (CRS), the degree of abnormalities on CXR correlates closely with known markers of disease severity. CRS may further be applied to predict patients who require oxygen supplementation during the course of their disease.

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design, Setting, and Participants Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Exposures Confirmed SARS-CoV-2 infection. Main Outcomes and Measures Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Results Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Conclusions and Relevance Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

Ocular manifestation in immunocompromised hosts can stem from a wide range of possible diagnoses. Endophthalmitis means bacterial or fungal infection inside the eye involving the vitreous and/or aq...

Streptococcus pneumoniae (S. pneumoniae) is a significant human bacterial pathogen and the major cause of pneumonia. In the post-antibiotic era, S. pneumoniae endocarditis is rare but carries a high risk of central nervous system (CNS) involvement. We present a case of invasive S. pneumoniae infection, which led to a cardioembolic stroke in a young man from septic emboli. Diagnosing a disseminated S. pneumoniae infection at an early stage is crucial and may improve patient outcomes.