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A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient’s family. Current decisions to take revolve around patient’s follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.
Arnaud Drouin; Marc Theberge; Sharon Liu; Allison Smither; Shelby Flaherty; Mark Zeller; Gregory Geba; Peter Reynaud; W. Rothwell; Alfred Luk; Di Tian; Matthew Boisen; Luis Branco; Kristian Andersen; James Robinson; Robert Garry; Dahlene Fusco. Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail. Viruses 2021, 13, 1202 .
AMA StyleArnaud Drouin, Marc Theberge, Sharon Liu, Allison Smither, Shelby Flaherty, Mark Zeller, Gregory Geba, Peter Reynaud, W. Rothwell, Alfred Luk, Di Tian, Matthew Boisen, Luis Branco, Kristian Andersen, James Robinson, Robert Garry, Dahlene Fusco. Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail. Viruses. 2021; 13 (7):1202.
Chicago/Turabian StyleArnaud Drouin; Marc Theberge; Sharon Liu; Allison Smither; Shelby Flaherty; Mark Zeller; Gregory Geba; Peter Reynaud; W. Rothwell; Alfred Luk; Di Tian; Matthew Boisen; Luis Branco; Kristian Andersen; James Robinson; Robert Garry; Dahlene Fusco. 2021. "Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail." Viruses 13, no. 7: 1202.
Infections with SARS-CoV-2 can progress toward multiple clinical outcomes, and the identification of factors associated with disease severity would represent a major advance to guide care and improve prognosis. We tested for associations between SARS-CoV-2 genomic variants from an international cohort of 2508 patients and mortality rates. Findings were validated in a second cohort. Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality. Three SNPs remained associated with mortality in a generalized linear model (GLM) that also included patient age, sex, geographic region, and month of sample collection. Multiple SNPs were confirmed in the validation cohort. These SNPs represent targets to assess the mechanisms underlying COVID-19 disease severity and warrant straightforward validation in functional studies.
Eric Dumonteil; Dahlene Fusco; Arnaud Drouin; Claudia Herrera. Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality. Viruses 2021, 13, 227 .
AMA StyleEric Dumonteil, Dahlene Fusco, Arnaud Drouin, Claudia Herrera. Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality. Viruses. 2021; 13 (2):227.
Chicago/Turabian StyleEric Dumonteil; Dahlene Fusco; Arnaud Drouin; Claudia Herrera. 2021. "Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality." Viruses 13, no. 2: 227.
Recent research suggests that SARS-CoV-2-infected individuals can be highly infectious while asymptomatic or pre-symptomatic, and that an infected person may infect 5.6 other individuals on average. This situation highlights the need for rapid, sensitive SARS-CoV-2 diagnostic assays capable of high-throughput operation that can preferably utilize existing equipment to facilitate broad, large-scale screening efforts. We have developed a CRISPR-based assay that can meet all these criteria. This assay utilizes a custom CRISPR Cas12a/gRNA complex and a fluorescent probe to detect target amplicons produced by standard RT-PCR or isothermal recombinase polymerase amplification (RPA), to allow sensitive detection at sites not equipped with real-time PCR systems required for qPCR diagnostics. We found this approach allowed sensitive and robust detection of SARS-CoV-2 positive samples, with a sample-to-answer time of ~50 min, and a limit of detection of 2 copies per sample. CRISPR assay diagnostic results obtained nasal swab samples of individuals with suspected COVID-19 cases were comparable to paired results from a CDC-approved quantitative RT-PCR (RT-qPCR) assay performed in a state testing lab, and superior to those produced by same assay in a clinical lab, where the RT-qPCR assay exhibited multiple invalid or inconclusive results. Our assay also demonstrated greater analytical sensitivity and more robust diagnostic performance than other recently reported CRISPR-based assays. Based on these findings, we believe that a CRISPR-based fluorescent application has potential to improve current COVID-19 screening efforts.
Zhen Huang; Di Tian; Yang Liu; Zhen Lin; Christopher J. Lyon; Weihua Lai; Dahlene Fusco; Arnaud Drouin; XiaoMing Yin; Tony Hu; Bo Ning. Ultra-sensitive and high-throughput CRISPR-p owered COVID-19 diagnosis. Biosensors and Bioelectronics 2020, 164, 112316 -112316.
AMA StyleZhen Huang, Di Tian, Yang Liu, Zhen Lin, Christopher J. Lyon, Weihua Lai, Dahlene Fusco, Arnaud Drouin, XiaoMing Yin, Tony Hu, Bo Ning. Ultra-sensitive and high-throughput CRISPR-p owered COVID-19 diagnosis. Biosensors and Bioelectronics. 2020; 164 ():112316-112316.
Chicago/Turabian StyleZhen Huang; Di Tian; Yang Liu; Zhen Lin; Christopher J. Lyon; Weihua Lai; Dahlene Fusco; Arnaud Drouin; XiaoMing Yin; Tony Hu; Bo Ning. 2020. "Ultra-sensitive and high-throughput CRISPR-p owered COVID-19 diagnosis." Biosensors and Bioelectronics 164, no. : 112316-112316.
Platelets can bind and phagocytose infectious microorganisms and so enable their transport for a prolonged time. To investigate the subcellular events of these interactions, platelets were incubated either with Staphylococcus aureus or with HIV and analyzed by electron microscopy (EM) and immuno-EM. HIV and bacteria internalization occurred exclusively within platelets showing morphological evidence of activation. Platelet activation enhanced the degree of bacterial internalization. Immunolabeling revealed that the engulfing vacuoles and the open canalicular system (OCS) were composed of distinct antigens. The engulfing vacuoles eventually became the site of prominent α-granule release. In platelets incubated with HIV, characteristic endocytic vacuoles were identified close to the plasma membrane, tightly surrounding 1 or 2 HIV particles. Virus particles were also located within the OCS. Immunogold labeling for the viral core protein p24 confirmed the presence of HIV within platelets. Finally, examination of platelets from a patient with acquired immunodeficiency syndrome and high viremia suggested that HIV endocytosis may also occur in vivo.
Tayebeh Youssefian; Arnaud Drouin; Jean-Marc Massé; Josette Guichard; Elisabeth M. Cramer. Host defense role of platelets: engulfment of HIV andStaphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 2002, 99, 4021 -4029.
AMA StyleTayebeh Youssefian, Arnaud Drouin, Jean-Marc Massé, Josette Guichard, Elisabeth M. Cramer. Host defense role of platelets: engulfment of HIV andStaphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood. 2002; 99 (11):4021-4029.
Chicago/Turabian StyleTayebeh Youssefian; Arnaud Drouin; Jean-Marc Massé; Josette Guichard; Elisabeth M. Cramer. 2002. "Host defense role of platelets: engulfment of HIV andStaphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation." Blood 99, no. 11: 4021-4029.