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.

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The COVID-19 pandemic has presented significant challenges for medical schools. It is critical to ensure final year medical school students are not delayed in their entry to the clinical workforce in times of healthcare crisis. However, proceeding with assessment to determine competency for graduation from medical school, and maintaining performance standards for graduating doctors is an unprecedented challenge under pandemic conditions. This challenge is hitherto uncharted territory for medical schools and there is scant guidance for medical educators. In early March 2020, Duke-National University Singapore Medical School embraced the challenge for ensuring competent final year medical students could complete their final year of studies and graduate on time, to enter the medical workforce in Singapore without delay. This paper provides details of how the final year clinical performance examinations were planned and conducted during the COVID-19 pandemic. The aim of the paper is to provide guidance to other medical schools in similar circumstances who need to plan and make suitable adjustments to clinical skills examinations under current pandemic conditions. The paper illustrates how it is possible to design and implement clinical skills examinations (OSCEs) to ensure the validity and reliability of high-stakes performance assessments whilst protecting the safety of all participants, minimising risk and maintaining defensibility to key stakeholders.

Objective: Staff surveillance is crucial during the containment phase of a pandemic to help reduce potential healthcare-associated transmission and sustain good staff morale. During an outbreak of SARS-COV-2 with community transmission, our institution used an integrated strategy for early detection and containment of COVID-19 cases among healthcare workers (HCWs).Methods: Our strategy comprised 3 key components: (1) enforcing reporting of HCWs with acute respiratory illness (ARI) to our institution's staff clinic for monitoring; (2) conducting ongoing syndromic surveillance to obtain early warning of potential clusters of COVID-19; and (3) outbreak investigation and management.Results: Over a 16-week surveillance period, we detected 14 cases of COVID-19 among HCWs with ARI symptoms. Two of the cases were linked epidemiologically and thus constituted a COVID-19 cluster with intrahospital HCW-HCW transmission; we also detected 1 family cluster and 2 clusters among HCWs who shared accommodation. No transmission to HCWs or patients was detected after containment measures were instituted. Early detection minimized the number of HCWs requiring quarantine, hence preserving continuity of service during an ongoing pandemic.Conclusions: An integrated surveillance strategy, outbreak management, and encouraging individual responsibility were successful in early detection of clusters of COVID-19 among HCWs. With ongoing local transmission, vigilance must be maintained for intrahospital spread in nonclinical areas where social mingling of HCWs occurs. Because most individuals with COVID-19 have mild symptoms, addressing presenteeism is crucial to minimize potential staff and patient exposure.

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