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1.
Religions ; 13(7):652, 2022.
Article in English | MDPI | ID: covidwho-1938954

ABSTRACT

The practice of prayer has been shown to predict various mental health outcomes, with different types of prayer accounting for different outcomes. Considering the numerous stressors facing seminary students, which have only intensified throughout the COVID-19 pandemic, prayer may be a common coping strategy for students who study theology, spiritual growth, and leadership. The present study investigates the role that different types of prayer may have in reducing anxiety, depression, and work burnout among seminary students. Experiential avoidance is proposed as a mediator such that specific types of prayer contribute to greater spiritual and characterological formation through staying engaged in the midst of struggle. Longitudinal data was collected from 564 graduate seminary students from 17 institutions accredited by the Association of Theological Schools. Based on previous research, we hypothesized that experiential avoidance would mediate the relationship between colloquial, liturgical, meditative, and petitionary prayer types and the negative mental health outcomes of anxiety, depression, and work burnout. Results confirmed significant negative relationships between colloquial, liturgical, and meditative prayer types and all three mental health indicators, fully mediated by experiential avoidance. Petitionary prayer was not significantly related to lower levels of mental health. These results indicate that engaging in certain prayer practices may be a protective factor by facilitating experiential engagement.

2.
mSphere ; 7(3): e0016422, 2022 06 29.
Article in English | MEDLINE | ID: covidwho-1923114

ABSTRACT

Bourbon virus (BRBV) was first discovered in 2014 in a fatal human case. Since then it has been detected in the tick Amblyomma americanum in the states of Missouri and Kansas in the United States. Despite the high prevalence of BRBV in ticks in these states, very few human cases have been reported, and the true infection burden of BRBV in the community is unknown. Here, we developed two virus neutralization assays, a vesicular stomatitis virus (VSV)-BRBV pseudotyped rapid assay and a BRBV focus reduction neutralization assay, to assess the seroprevalence of BRBV neutralizing antibodies in human sera collected in 2020 in St. Louis, MO. Of 440 human serum samples tested, three (0.7%) were able to potently neutralize both VSV-BRBV and wild-type BRBV. These findings suggest that human infections with BRBV are more common than previously recognized. IMPORTANCE Since the discovery of the Bourbon virus (BRBV) in 2014, a total of five human cases have been identified, including two fatal cases. BRBV is thought to be transmitted by the lone star tick, which is prevalent in the eastern, southeastern, and midwestern United States. BRBV has been detected in ticks in Missouri and Kansas, and serological evidence suggests that it is also present in North Carolina. However, the true infection burden of BRBV in humans is not known. In the present study, we developed two virus neutralization assays to assess the seroprevalence of BRBV-specific antibodies in human sera collected in 2020 in St. Louis, MO. We found that a small subset of individuals are seropositive for neutralizing antibodies against BRBV. Our data suggest that BRBV infection in humans is more common than previously thought.


Subject(s)
Thogotovirus , Ticks , Animals , Antibodies, Neutralizing , Humans , Missouri/epidemiology , Seroepidemiologic Studies , United States
3.
Eur Radiol ; 2022 Jul 02.
Article in English | MEDLINE | ID: covidwho-1919771

ABSTRACT

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

4.
Diagnostics (Basel) ; 12(5)2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1875516

ABSTRACT

Vertical flow assays (VFAs) or flow-through assays have emerged as an alternate type of paper-based assay due to their faster detection time, larger sample volume capacity, and significantly higher multiplexing capabilities. They have been successfully employed to detect several different targets (polysaccharides, protein, and nucleic acids), although in a limited number of samples (serum, whole blood, plasma) compared to the more commonly known lateral flow assays (LFAs). The operation of a VFA relies mainly on gravity, coupled with capillary action or external force to help the sample flow through layers of stacked pads. With recent developments in this field, multiple layers of pads and signal readers have been optimized for more user-friendly operation, and VFAs have achieved a lower limit of detection for various analytes than the gold-standard methods. Thus, compared to the more widely used LFA, the VFA demonstrates certain advantages and is becoming an increasingly popular platform for obtaining qualitative and quantitative results in low-resource settings. Considering the wide application of gold nanoparticles (GNPs) in VFAs, we will mostly discuss (1) the design of GNP-based VFA along with its associated advantages/disadvantages, (2) fabrication and optimization of GNP-based VFAs for applications, and (3) the future outlook of flow-based assays for point-of-care testing (POCT) diagnostics.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335257

ABSTRACT

The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs. Compensatory substitutions that restored the G-C base-pair enabled recovery of VA1. For HAstV1, a partial deletion of the s2m resulted in decreased viral titers compared to wild-type virus, and reduced activity in a replicon system. In contrast, deletion or mutation of the SARS-CoV-2 s2m had no effect on the ability to rescue the virus, growth in vitro , or growth in Syrian hamsters. Our study demonstrates the importance of the s2m is virus-dependent.

6.
Circ Cardiovasc Qual Outcomes ; 15(4): e008900, 2022 04.
Article in English | MEDLINE | ID: covidwho-1807749
7.
Journal of Psychology and Christianity ; 40(1):78-83, 2021.
Article in English | ProQuest Central | ID: covidwho-1762720

ABSTRACT

[...]this paper explores how recent advancements in research on positive psychology and the psychology of religion and spirituality provide a fertile context for faith communities and scientific communities to collaborate together towards the shared vision of community renewal-a vision of community renewal that is grounded in Christian character and formation as well as empirical science. Even Christ Himself is intimately familiar with what it is like to occupy a liminal space (c.f. Matt. 26:36-46). [...]from the standpoint of our Christian faith, this is a familiar space for Christians to occupy because our present existence as the children of God here on earth similarly leads us into this familiar tension between the past and the future. [...]this special issue of the Journal of Psychology and Christianity edited by James Sells and Mark Newmeyer can be understood a special issue on liminality-as it applies to the entire field of Christian mental health. [...]from the many esteemed colleagues who have not only contributed to this special issue, but also made significant and unique contributions to our field, we receive different glimpses, different perspectives on how we might understand and hold this tension between the "what was" in Christian mental health and the "next." [...]reading these works personally earlier in life (e.g., Eric Johnson and Stanton Jones' (2000) Psychology & Christianity: Four Views) provided me with rich foundational knowledge that was pivotal in shaping my own journey into this field.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310787

ABSTRACT

Critically ill patients with the Coronavirus disease 2019 (COVID-19) are dying in isolation without the comfort of their family or other social support in unprecedented numbers. Recently, healthcare teams at COVID-19 epicenters have been inundated with critically ill patients. Patients isolated for COVID-19 have had no contact with their family or loved ones and may have likely experienced death without closure. This situation highlights concerns about the psychological and spiritual well-being of patients with COVID-19 and their families, as they permanently part ways. While palliative care has advanced to address these patients' needs adequately, the COVID-19 pandemic presents several barriers that force healthcare teams to deprioritize these essential aspects of patient care. The severe acute respiratory syndrome (SARS) outbreak in 2003 gave us a glimpse of these challenges as these patients were also isolated in hospitals. Here, we discuss the importance of the biopsychosocial spiritual model in end-of-life care and its implications on patients dying with COVID-19. Furthermore, we outline an integrative approach to address the unique and holistic needs of critically ill patients dying with COVID-19. These include intentional and increased coordination with trained palliative care staff, early and frequent goals of care including discussion of end-of-life plans, broader use of technology to improve connectedness and shared decision making with patients’ families.

10.
Immunity ; 54(10): 2399-2416.e6, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1364126

ABSTRACT

With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.


Subject(s)
Antibodies, Neutralizing/immunology , Epitopes/immunology , SARS-CoV-2/immunology , Amino Acid Motifs , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/therapeutic use , COVID-19/prevention & control , COVID-19/virology , Epitopes/chemistry , Epitopes/metabolism , Humans , Immunoglobulin Light Chains/chemistry , Immunoglobulin Light Chains/metabolism , Mice , Neutralization Tests , Protein Domains , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
11.
mSphere ; 6(4): e0045021, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1341307

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity was assessed for 3,066 individuals visiting hospitals in St. Louis, Missouri, during July 2020, November 2020, or January 2021. Seropositivity in children increased from 5.22% in July to 21.16% in January. In the same time frame, seropositivity among adults increased from 4.52% to 19.03%, prior to initiation of mass vaccination. IMPORTANCE This study determined the percentage of children and adult samples from the St. Louis metropolitan area in Missouri with SARS-CoV-2 antibodies during three collection periods spanning July 2020 to January 2021. By January 2021, 20.68% of the tested individuals had antibodies. These results show the evolution of the SARS-CoV-2 pandemic in St. Louis, Missouri, and provide a snapshot of the extent of infection just prior to the start of mass vaccination.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Missouri , Pandemics/prevention & control , Seroepidemiologic Studies , Young Adult
12.
Stroke Vasc Neurol ; 5(3): 279-284, 2020 09.
Article in English | MEDLINE | ID: covidwho-1318202

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection. MATERIALS AND METHODS: Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared. RESULTS: Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%). CONCLUSION: Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.


Subject(s)
Betacoronavirus/pathogenicity , Cerebrovascular Disorders/virology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Acute Disease , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19 , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/mortality , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome
14.
Stroke Vasc Neurol ; 5(2): 180-184, 2020 06.
Article in English | MEDLINE | ID: covidwho-1318199

ABSTRACT

BACKGROUND: The COVID-19 pandemic has already stressed the healthcare system in the world. Many hospitals have been overwhelmed by the large number of patients with COVID-19. Due to the shortage of equipment and personnel and the highly contagious nature of COVID-19, many other healthcare services are on hold. However, at Beijing Tiantan Hospital, a rapid response system has been in place so that routine care is not interrupted. We, therefore, would like to share our hospital-wide prevention and management policy during this pandemic to help other healthcare systems to function in this crisis. METHOD: Tiantan hospital is one of the leading neuroscience institutions in the world. With 1650 beds, its annual inpatient admission exceeds 30 000 patients. Its COVID-19 rapid response policy was reviewed for its functionality. RESULTS: There are nine key components of this policy: an incident management system; a comprehensive infection prevention and control, outpatient triage and flow system; a designated fever clinic; patient screening and administration; optimised surgical operations, enhanced nucleic acid testing; screening of returning employees; and a supervision and feedback system. In addition, a specific protocol was designed for treating patients with acute stroke. CONCLUSION: A comprehensive policy is helpful to protect the employee from infection and to provide quality and uninterrupted care to all who need these, including patients with acute ischaemic stroke.


Subject(s)
Betacoronavirus/pathogenicity , Brain Ischemia/therapy , Coronavirus Infections/therapy , Infection Control/methods , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Occupational Exposure/prevention & control , Pneumonia, Viral/therapy , Stroke/therapy , Beijing , Brain Ischemia/diagnosis , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Critical Pathways , Delivery of Health Care, Integrated , Health Services Needs and Demand , Host-Pathogen Interactions , Humans , Needs Assessment , Occupational Health , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Stroke/diagnosis , Triage
15.
Stroke Vasc Neurol ; 5(2): 146-151, 2020 06.
Article in English | MEDLINE | ID: covidwho-1318197

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or 'virus spreaders'. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID-19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.


Subject(s)
Betacoronavirus/pathogenicity , Central Nervous System Infections/therapy , Central Nervous System/virology , Clinical Laboratory Techniques/standards , Coronavirus Infections/therapy , Neurologists/standards , Pneumonia, Viral/therapy , COVID-19 , COVID-19 Testing , Central Nervous System/physiopathology , Central Nervous System Infections/diagnosis , Central Nervous System Infections/physiopathology , Central Nervous System Infections/virology , Consensus , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Early Diagnosis , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Predictive Value of Tests , Prognosis , SARS-CoV-2
16.
J Clin Microbiol ; 59(7): e0007521, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1276884

ABSTRACT

Diagnostic assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for patient management, infection prevention, and the public health response for coronavirus disease 2019 (COVID-19). The efficacy and reliability of these assays are of paramount importance in both tracking and controlling the spread of the virus. Real-time reverse transcription-PCR (RT-PCR) assays rely on a fixed genetic sequence for primer and probe binding. Mutations can potentially alter the accuracy of these assays and lead to unpredictable analytical performance characteristics and false-negative results. Here, we identify a G-to-U transversion (nucleotide 26372) in the SARS-CoV-2 E gene in three specimens with reduced viral detection efficiency using a widely available commercial assay. Further analysis of the public GISAID repository led to the identification of 18 additional genomes with this mutation, which reflect five independent mutational events. This work supports the use of dual-target assays to reduce the number of false-negative PCR results.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , Sensitivity and Specificity
17.
Nature ; 596(7870): 103-108, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275940

ABSTRACT

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/pharmacology , Antibodies, Viral/therapeutic use , COVID-19/virology , Neutralization Tests , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , Chlorocebus aethiops , Female , Humans , Male , Mesocricetus/immunology , Mesocricetus/virology , Mice , Mice, Transgenic , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , SARS-CoV-2/genetics , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
18.
Anesthesiol Clin ; 39(2): 363-377, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1240167

ABSTRACT

In March 2020, the COVID-19 pandemic reached New York City, resulting in thousands of deaths over the following months. Because of the exponential spread of disease, the New York City hospital systems became rapidly overwhelmed. The Department of Anesthesiology at New York Presbyterian (NYP)-Columbia continued to offer anesthesia services for obstetrics and emergency surgery, while redirecting the rest of its staff to the expanded airway management role and the creation of the largest novel intensive care unit in the NYP system. Tremendous innovation and optimization were necessary in the face of material, physical, and staffing constraints.


Subject(s)
Anesthesia/statistics & numerical data , Anesthesiology/organization & administration , COVID-19 , Health Resources/organization & administration , Hospitals , Pandemics , Hospital Departments/organization & administration , Humans , New York City , Operating Rooms/organization & administration
19.
Res Sq ; 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1237037

ABSTRACT

Rapidly-emerging variants jeopardize antibody-based countermeasures against SARS-CoV-2. While recent cell culture experiments have demonstrated loss of potency of several anti-spike neutralizing antibodies against SARS-CoV-2 variant strains1-3, the in vivo significance of these results remains uncertain. Here, using a panel of monoclonal antibodies (mAbs) corresponding to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron, and Lilly we report the impact on protection in animals against authentic SARS-CoV-2 variants including WA1/2020 strains, a B.1.1.7 isolate, and chimeric strains with South African (B.1.351) or Brazilian (B.1.1.28) spike genes. Although some individual mAbs showed reduced or abrogated neutralizing activity against B.1.351 and B.1.1.28 viruses with E484K spike protein mutations in cell culture, low prophylactic doses of mAb combinations protected against infection in K18-hACE2 transgenic mice, 129S2 immunocompetent mice, and hamsters without emergence of resistance. Two exceptions were mAb LY-CoV555 monotherapy which lost all protective activity in vivo, and AbbVie 2B04/47D11, which showed partial loss of activity. When administered after infection as therapy, higher doses of mAb cocktails protected in vivo against viruses displaying a B.1.351 spike gene. Thus, many, but not all, of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing SARS-CoV-2 variant strains.

20.
J Clin Microbiol ; 59(7): e0007521, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1203933

ABSTRACT

Diagnostic assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for patient management, infection prevention, and the public health response for coronavirus disease 2019 (COVID-19). The efficacy and reliability of these assays are of paramount importance in both tracking and controlling the spread of the virus. Real-time reverse transcription-PCR (RT-PCR) assays rely on a fixed genetic sequence for primer and probe binding. Mutations can potentially alter the accuracy of these assays and lead to unpredictable analytical performance characteristics and false-negative results. Here, we identify a G-to-U transversion (nucleotide 26372) in the SARS-CoV-2 E gene in three specimens with reduced viral detection efficiency using a widely available commercial assay. Further analysis of the public GISAID repository led to the identification of 18 additional genomes with this mutation, which reflect five independent mutational events. This work supports the use of dual-target assays to reduce the number of false-negative PCR results.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , Sensitivity and Specificity
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