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1.
JCI Insight ; 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1950563

ABSTRACT

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

2.
Am J Respir Crit Care Med ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1932885

ABSTRACT

RATIONALE: The incidence and sites of mucus accumulation, and molecular regulation of mucin gene expression, in COVID-19 lung disease have not been reported. OBJECTIVES: Characterize incidence of mucus accumulation and the mechanisms mediating mucin hypersecretion in COVID-19 lung disease. METHODS: Airway mucus and mucins were evaluated in COVID-19 autopsy lungs by AB-PAS and immunohistochemical staining, RNA in situ hybridization, and spatial transcriptional profiling. SARS-CoV-2-infected human bronchial epithelial (HBE) cultures were utilized to investigate mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. MEASUREMENTS AND MAIN RESULTS: MUC5B and variably MUC5AC RNA levels were increased throughout all airway regions of COVID-19 autopsy lungs, notably in the sub-acute/chronic disease phase following SARS-CoV-2 clearance. In the distal lung, MUC5B-dominated mucus plugging was observed in 90% of COVID-19 subjects in both morphologically identified bronchioles and microcysts, and MUC5B accumulated in damaged alveolar spaces. SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days post inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days post inoculation. SARS-CoV-2 infection of HBE cultures induced expression of EGFR ligands and inflammatory cytokines (e.g., IL-1α/ß) associated with mucin gene regulation. Inhibiting EGFR/IL-1R pathways, or dexamethasone administration, reduced SARS-CoV-2-induced mucin expression. CONCLUSIONS: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation post SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

3.
EBioMedicine ; 77: 103940, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1881926

ABSTRACT

BACKGROUND: Limited knowledge exists in post-partum women regarding durability of SARS-CoV-2 vaccine-induced antibody responses and their neutralising ability against SARS-CoV-2 variants of concern (VOC). METHODS: We elucidated longitudinal mRNA vaccination-induced antibody profiles of 13 post-partum and 13 non-post-partum women (control). FINDINGS: The antibody neutralisation titres against SARS-CoV-2 WA-1 strain were comparable between post-partum and non-post-partum women and these levels were sustained up to four months post-second vaccination in both groups. However, neutralisation titers declined against several VOCs, including Beta and Delta. Higher antibody binding was observed against SARS-CoV-2 receptor-binding domain (RBD) mutants with key VOC amino acids when tested with post-second vaccination plasma from post-partum women compared with controls. Importantly, post-vaccination plasma antibody affinity against VOCs RBDs was significantly higher in post-partum women compared with controls. INTERPRETATION: This study demonstrates that there is a differential vaccination-induced immune responses in post-partum women compared with non-post-partum women, which could help inform future vaccination strategies for these groups. FUNDING: The antibody characterisation work described in this manuscript was supported by FDA's Medical Countermeasures Initiative (MCMi) grant #OCET 2021-1565 to S.K and intramural FDA-CBER COVID-19 supplemental funds.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , Antibody Affinity , COVID-19/prevention & control , Female , Humans , Immunoglobulin G , Postpartum Period , SARS-CoV-2/genetics , Vaccines, Synthetic
4.
EBioMedicine ; 77, 2022.
Article in English | EuropePMC | ID: covidwho-1743737

ABSTRACT

Summary Background Limited knowledge exists in post-partum women regarding durability of SARS-CoV-2 vaccine-induced antibody responses and their neutralising ability against SARS-CoV-2 variants of concern (VOC). Methods We elucidated longitudinal mRNA vaccination-induced antibody profiles of 13 post-partum and 13 non-post-partum women (control). Findings The antibody neutralisation titres against SARS-CoV-2 WA-1 strain were comparable between post-partum and non-post-partum women and these levels were sustained up to four months post-second vaccination in both groups. However, neutralisation titers declined against several VOCs, including Beta and Delta. Higher antibody binding was observed against SARS-CoV-2 receptor-binding domain (RBD) mutants with key VOC amino acids when tested with post-second vaccination plasma from post-partum women compared with controls. Importantly, post-vaccination plasma antibody affinity against VOCs RBDs was significantly higher in post-partum women compared with controls. Interpretation This study demonstrates that there is a differential vaccination-induced immune responses in post-partum women compared with non-post-partum women, which could help inform future vaccination strategies for these groups.

5.
6.
Clin Infect Dis ; 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1700720

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (Covid-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response and immunothrombosis. Fostamatinib, is a novel spleen tyrosine kinase inhibitor we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with Covid-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared to 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs. -2.6 ± 0.4, P = .035) and the median length in the ICU was 3 days in the fostamatinib group vs. 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs. 28, P = .027). There were trends towards more rapid reductions in C-reactive protein, D-dimer, fibrinogen and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. These results warrant further validation in larger confirmatory trials.

7.
Front Immunol ; 12: 779026, 2021.
Article in English | MEDLINE | ID: covidwho-1581330

ABSTRACT

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.


Subject(s)
COVID-19/complications , Myocarditis/pathology , Myocarditis/virology , Systemic Inflammatory Response Syndrome/pathology , T-Lymphocytes/immunology , Adult , COVID-19/immunology , COVID-19/pathology , Humans , Male , Myocarditis/immunology , RNA, Viral/analysis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/immunology
8.
Nat Immunol ; 23(1): 62-74, 2022 01.
Article in English | MEDLINE | ID: covidwho-1514418

ABSTRACT

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.


Subject(s)
Interferon-gamma/immunology , Interleukin-10/immunology , SARS-CoV-2/immunology , Th1 Cells/immunology , Vitamin D/metabolism , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Basic-Leucine Zipper Transcription Factors/metabolism , Bronchoalveolar Lavage Fluid/cytology , COVID-19/immunology , COVID-19/pathology , Complement C3a/immunology , Complement C3b/immunology , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Lymphocyte Activation/immunology , Receptors, Calcitriol/metabolism , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , STAT3 Transcription Factor/metabolism , Signal Transduction/immunology , Transcription, Genetic/genetics
9.
Clin Infect Dis ; 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1381001

ABSTRACT

BACKGROUND: Coronavirus Disease 2019 (Covid-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response and immunothrombosis. Fostamatinib, is a novel spleen tyrosine kinase inhibitor we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with Covid-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared to 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs. -2.6 ± 0.4, P = .035) and the median length in the ICU was 3 days in the fostamatinib group vs. 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs. 28, P = .027). There were trends towards more rapid reductions in C-reactive protein, D-dimer, fibrinogen and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. These results warrant further validation in larger confirmatory trials.

10.
J Intensive Care Med ; 36(10): 1201-1208, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305547

ABSTRACT

BACKGROUND: Corticosteroids are part of the treatment guidelines for COVID-19 and have been shown to improve mortality. However, the impact corticosteroids have on the development of secondary infection in COVID-19 is unknown. We sought to define the rate of secondary infection in critically ill patients with COVID-19 and determine the effect of corticosteroid use on mortality in critically ill patients with COVID-19. STUDY DESIGN AND METHODS: One hundred and thirty-five critically ill patients with COVID-19 admitted to the Intensive Care Unit (ICU) at the University of Maryland Medical Center were included in this single-center retrospective analysis. Demographics, symptoms, culture data, use of COVID-19 directed therapies, and outcomes were abstracted from the medical record. The primary outcomes were secondary infection and mortality. Proportional hazards models were used to determine the time to secondary infection and the time to death. RESULTS: The proportion of patients with secondary infection was 63%. The likelihood of developing secondary infection was not significantly impacted by the administration of corticosteroids (HR 1.45, CI 0.75-2.82, P = 0.28). This remained consistent in sub-analysis looking at bloodstream, respiratory, and urine infections. Secondary infection had no significant impact on the likelihood of 28-day mortality (HR 0.66, CI 0.33-1.35, P = 0.256). Corticosteroid administration significantly reduced the likelihood of 28-day mortality (HR 0.27, CI 0.10-0.72, P = 0.01). CONCLUSION: Corticosteroids are an important and lifesaving pharmacotherapeutic option in critically ill patients with COVID-19, which have no impact on the likelihood of developing secondary infections.


Subject(s)
COVID-19 , Coinfection , Adrenal Cortex Hormones , Critical Illness , Humans , Intensive Care Units , Retrospective Studies , SARS-CoV-2
11.
PLoS Pathog ; 17(4): e1009431, 2021 04.
Article in English | MEDLINE | ID: covidwho-1172888

ABSTRACT

Tracking evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within infected individuals will help elucidate coronavirus disease 2019 (COVID-19) pathogenesis and inform use of antiviral interventions. In this study, we developed an approach for sequencing the region encoding the SARS-CoV-2 virion surface proteins from large numbers of individual virus RNA genomes per sample. We applied this approach to the WA-1 reference clinical isolate of SARS-CoV-2 passaged in vitro and to upper respiratory samples from 7 study participants with COVID-19. SARS-CoV-2 genomes from cell culture were diverse, including 18 haplotypes with non-synonymous mutations clustered in the spike NH2-terminal domain (NTD) and furin cleavage site regions. By contrast, cross-sectional analysis of samples from participants with COVID-19 showed fewer virus variants, without structural clustering of mutations. However, longitudinal analysis in one individual revealed 4 virus haplotypes bearing 3 independent mutations in a spike NTD epitope targeted by autologous antibodies. These mutations arose coincident with a 6.2-fold rise in serum binding to spike and a transient increase in virus burden. We conclude that SARS-CoV-2 exhibits a capacity for rapid genetic adaptation that becomes detectable in vivo with the onset of humoral immunity, with the potential to contribute to delayed virologic clearance in the acute setting.


Subject(s)
COVID-19 , Epitopes , Immunity, Humoral , Mutation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19/genetics , COVID-19/immunology , Cell Line , Epitopes/genetics , Epitopes/immunology , Female , High-Throughput Nucleotide Sequencing , Humans , Male , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
12.
J Pediatric Infect Dis Soc ; 9(6): 769-771, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1072398

ABSTRACT

Evidence for in utero transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is growing but not definitive. We present a case of neonatal infection that supports in utero transmission of SARS-CoV-2 and provides insight into the hematogenous spread from mother to fetus.


Subject(s)
COVID-19/transmission , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/virology , COVID-19/complications , COVID-19 Testing , Female , Fetal Blood/virology , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/etiology , Male , Placenta/virology , Pregnancy , RNA, Viral/blood , RNA, Viral/urine , SARS-CoV-2/genetics
13.
Crit Care Med ; 49(3): e219-e234, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1069322

ABSTRACT

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/therapy , Critical Care , Dexamethasone/therapeutic use , Disease Management , Intensive Care Units , Practice Guidelines as Topic , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Anticoagulants , Evidence-Based Medicine , Hemodynamics , Humans , Hydroxychloroquine , Immunization, Passive , Patient Positioning , Ventilation
14.
J Infect Dis ; 223(6): 981-984, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-990724

ABSTRACT

Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in coronavirus disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrated that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.


Subject(s)
COVID-19/drug therapy , Extracellular Traps/drug effects , Neutrophils/drug effects , Oxazines/pharmacology , Pyridines/pharmacology , Aminopyridines , COVID-19/blood , COVID-19/pathology , Humans , Morpholines , Pyrimidines , SARS-CoV-2/isolation & purification
15.
Crit Care Med ; 48(6): e440-e469, 2020 06.
Article in English | MEDLINE | ID: covidwho-685042

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.


Subject(s)
Coronavirus Infections/therapy , Intensive Care Units/organization & administration , Pneumonia, Viral/therapy , Practice Guidelines as Topic/standards , Betacoronavirus , COVID-19 , Critical Illness , Diagnostic Techniques and Procedures/standards , Humans , Infection Control/methods , Infection Control/standards , Intensive Care Units/standards , Pandemics , Respiration, Artificial/methods , Respiration, Artificial/standards , SARS-CoV-2 , Shock/therapy
16.
J Infect Dis ; 222(2): 206-213, 2020 06 29.
Article in English | MEDLINE | ID: covidwho-618807

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. METHODS: Quantitative measurements of plasma or serum antibodies to the nucleocapsid and spike proteins were analyzed using luciferase immunoprecipitation system assays in 100 cross-sectional or longitudinal samples from patients with SARS-CoV-2 infection. A subset of samples was tested both with and without heat inactivation. RESULTS: At >14 days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, whereas antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from 6 patients with COVID-19 showed anti-nucleocapsid and spike protein antibodies appearing between days 8 and 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2, compared with immunocompetent patients. CONCLUSIONS: Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples with a luciferase immunoprecipitation system assay is a safe and sensitive method for detecting SARS-CoV-2 antibodies.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Clinical Laboratory Techniques , Coronavirus Infections/immunology , Immunoprecipitation , Nucleocapsid Proteins/immunology , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Coronavirus Nucleocapsid Proteins , Female , Hot Temperature , Humans , Immunocompetence , Immunocompromised Host , Luciferases , Male , Middle Aged , Pandemics , Phosphoproteins , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , Time Factors
17.
Intensive Care Med ; 46(5): 854-887, 2020 05.
Article in English | MEDLINE | ID: covidwho-17690

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.


Subject(s)
Coronavirus Infections/therapy , Critical Care/standards , Intensive Care Units/standards , Pneumonia, Viral/therapy , Sepsis/therapy , COVID-19 , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Sepsis/diagnosis , Sepsis/etiology , Survivors
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