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.
Objectives: Patients with COVID-19 may present with respiratory syndromes indistinguishable from common viruses. This poses a challenge for early detection during triage in the emergency department (ED). Over a 3month period, our ED aimed to minimize nosocomial transmission by using broader suspect case criteria for better detection and using appropriate personal protective equipment (PPE) for health care workers (HCWs).Methods: All ED admissions with respiratory syndromes over a 3-month period were tested for COVID-19. The sensitivity and specificity of screening criteria in detecting COVID-19 were assessed. A risk-stratified approach was adopted for PPE usage in the ED, based on high-risk "fever areas" and lower-risk zones. When a case of COVID-19 was confirmed, surveillance was conducted for potentially exposed patients and HCWs.Results: A total of 1,841 cases presenting with respiratory syndromes required admission over the study period.Among these, 70 cases of COVID-19 were subsequently confirmed. The majority (84.2%, 59/70) were detected at ED triage because they fulfilled suspect case criteria. Of these, 34 met the official screening criteria; an additional 25 were detected by the broader internal screening criteria. Over the 12-week period, the cumulative sensitivity of internal screening criteria was 84.3% (95% confidence interval [CI] = 73.6% to 91.9%), whereas the sensitivity of the official screening criteria was 48.6% (95% CI = 36.4% to 60.8%). Given the broadened internal criteria, the preexisting ED "fever area" was insufficient and had to be expanded. However, there were no cases of nosocomial transmission from intra-ED exposure, despite extensive surveillance.Conclusion: Frontline physicians need to be given leeway to decide on the disposition of cases based on clinical suspicion during an ongoing outbreak of COVID-19. If a broader criterion is used at ED triage, ED facilities and isolation facilities need to be readied to accommodate a surge of suspect cases. Usage of appropriate PPE is essential in minimizing nosocomial transmission.
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.
developed thrombosis, our patients' CWA parameters remained remarkably high despite the use of thromboprophylaxis during their ICU stay. It is possible that CWA and other thrombin generation assays might not be sensitive enough to detect the haemostatic changes caused by the standard prophylactic dose of low molecular weight heparin.All three patients recovered from COVID-19 infection.Thatour findings of markedly raised CWA parameters in critically ill infected cases are possibly consistent with hypercoagulability is not unexpected. Such patients exhibit hyperinflammation and cytokine overdrive, and extensive crosstalk is known to exist in the cytokines, the inflammatory system, and coagulation. 6 Critically ill COVID-19 patients have been shown to have increased proinflammatory cytokines including IL-2 and TNF-α, 4 and these factors could upregulate the coagulation system. 6 We speculate that this could partially account for the CWA changes observed.Although our findings are limited by the relatively few patients and data points and by the lack of other correlation studies with other coagulation assays, we believe there are still valuable points to take away. Many of the specialized and research haemostatic assays cannot be safely and easily performed on samples collected from COVID-19 patients in view of laboratory biosafety concerns. As COVID-19 infection is spreading relentlessly worldwide, there is an urgent need for rapid and readily accessible biomarkers that can aid clinical stratification and management. So, CWA represents a simple, automated and rapid test, which fulfills these biosafety criteria. Whenever an aPTT is performed, an aPTT waveform is generated automatically by commonly used optical analysers worldwide.In conclusion, the rise of CWA parameters precedes and coincides with ICU admission and warrant further study to confirm its utility in the routine management of COVID-19 patients.
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