Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.

Background Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited capacity for specialized nucleic acid–based reverse transcription polymerase chain reaction (PCR) testing. Methods This retrospective case-control study involves subjects (7–98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike’s information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation. Results The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65. Conclusions Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.

Background Prolonged fever is associated with adverse outcomes in dengue viral infection. Similar fever patterns are observed in COVID-19 with unclear significance. Methods We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever>7 days) and saddleback fever (recurrence of fever, lasting less than 24 hours, after defervescence beyond day 7 of illness). Fever was defined as a temperature of ≥60.0oC. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation and mortality. Results A total of 142 patients were included in the study. 12.7% (18/142) of cases had prolonged fever and 9.9% (14/142) had saddleback fever. Those with prolonged fever had a median duration of fever for 10 days (IQR 9–11 days) for prolonged fever cases, while fever recurred at a median of 10 days (IQR 8–12 days) for those with saddleback fever. Both prolonged (27.8% vs 0.9%, p <0.01) and saddleback fever (14.3% vs 0.9%, p= 0.03) were associated with hypoxia compared to controls. Cases with prolonged fever were also more likely to require ICU admission compared to controls (11.1% vs 0.9%) (p=0.05). Patients with prolonged fever had higher IP-10 and lower IL-1α levels compared to those with saddleback fever at the early acute phase of disease. Conclusion Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Patients with saddleback fever appeared to have good outcomes regardless of the fever.

BackgroundIn May 2015, we noticed an increase in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in the Medical Intensive Care Unit (MICU). To investigate this, we studied the extent of environmental contamination and subsequent onward clonal transmission of CRAB.MethodsWe conducted a one-day point prevalence screening (PPS) of the patients and environment in the MICU. We screened patients using endotracheal tube aspirates and swabs from nares, axillae, groin, rectum, wounds, and exit sites of drains. We collected environmental samples from patients’ rooms and environment outside the patients’ rooms. CRAB isolates from the PPS and clinical samples over the subsequent one month were studied for genetic relatedness by whole genome sequencing (WGS).ResultsWe collected 34 samples from seven patients and 244 samples from the environment. On the day of PPS, we identified 8 CRAB carriers: 3 who screened positive and 5 previously known clinical infections. We detected environmental contamination in nearly two-thirds of the rooms housing patients with CRAB. WGS demonstrated genetic clustering of isolates within rooms but not across rooms. We analysed 4 CRAB isolates from clinical samples following the PPS. One genetically-related CRAB was identified in the respiratory sample of a patient with nosocomial pneumonia, who was admitted to the MICU five days after the PPS.ConclusionThe extensive environmental colonization of CRAB by patients highlights the importance of environmental hygiene. The transmission dynamics of CRAB needs further investigation.

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BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Background The performance of rRT-PCR for SARS-CoV-2 varies with sampling site(s), illness stage and infection site. Methods Unilateral nasopharyngeal, nasal mid-turbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspect or confirmed cases of COVID-19.True positives were defined as patients with at least one SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, till discharge. Diagnostic performance was assessed and extrapolated for site combinations. Results We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, mid-turbinate, 62%, and saliva, 38-52%. Clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 95%, 88%, 72%, and 44-56% if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28-44% if >7 days of illness. Comparing patients with URTI vs. pneumonia, clinical sensitivity for nasopharyngeal, throat, mid-turbinate and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43-54% vs 26-45%. A combination of nasopharyngeal plus throat or mid-turbinate plus throat specimen afforded overall clinical sensitivities of 89-92%, this rose to 96% for persons with URTI and 98% for persons <7 days from illness onset. Conclusion Nasopharyngeal followed by throat specimens offer the highest clinical sensitivity for COVID-19 diagnosis in early illness. Clinical sensitivity improves and is similar when either mid-turbinate or nasopharyngeal specimens are combined with throat specimens. Upper respiratory specimens perform poorly if taken after the first week of illness or if there is pneumonia.