32 research outputs found
Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study
There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.6 (IQR 2.3–4.8) versus 26.4 h (IQR 21.4–31.4, p < 0.001), with 32 (21.5%) positive and 117 (78.5%) negative. Cohen’s κ correlation between tests is 0.96 (95% CI 0.91–1.00). When comparing nearly 1,000 tests pre- and post-implementation, the median time to definitive bed placement from admission is 23.4 (8.6-41.9) versus 17.1 h (9.0–28.8), p = 0.02. Mean length of stay on COVID-19 “holding” wards is 58.5 versus 29.9 h (p < 0.001). POC testing increases isolation room availability, avoids bed closures, allows discharge to care homes, and expedites access to hospital procedures. POC testing could mitigate the impact of COVID-19 on hospital systems
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients
SARS-CoV-2 evolution during treatment of chronic infection
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major
54 antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising
55 antibodies in an immune suppressed individual treated with convalescent plasma, generating
56 whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was
57 observed in the overall viral population structure following two courses of remdesivir over the
58 first 57 days. However, following convalescent plasma therapy we observed large, dynamic
59 virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and
60 H69/V70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred
61 serum antibodies diminished, viruses with the escape genotype diminished in frequency, before
62 returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape
63 double mutant bearing H69/V70 and D796H conferred modestly decreased sensitivity to
64 convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be
65 the main contributor to decreased susceptibility but incurred an infectivity defect. The
66 H69/V70 single mutant had two-fold higher infectivity compared to wild type, possibly
67 compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS68
CoV-2 during convalescent plasma therapy associated with emergence of viral variants with
69 evidence of reduced susceptibility to neutralising antibodies.COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients
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Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
Abstract: The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
Abstract: The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients
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Viral infections in critical care: a narrative review.
Viral infections form a substantial part of the intensive care workload, even before the recent and ongoing COVID-19 pandemic. The growing availability of molecular diagnostics for viral infections has led to increased recognition of these pathogens. This additional information, however, provides new challenges for interpretation and management. As the SARS-CoV-2 pandemic has amply demonstrated, the emergence and global spread of novel viruses are likely to provide continued challenges for critical care physicians into the future. This article will provide an overview of viral infections relevant to the critical care physician, discussing the diagnosis and management of respiratory viral infections, blood borne and enteric viruses. We will also discuss herpesviridae complications, commonly seen due to reactivation of latent infections. Further, we explore some rarer and emerging viruses, including recognition of viral haemorrhagic fevers, and briefly discuss post-viral syndromes which may present to the intensive care unit. Finally, we will discuss infection control and its importance in preventing nosocomial viral transmission