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Samira Mubareka
Sunnybrook Health Sciences Centre, 2075 Bayview Av, Toronto, ON Canada M4N 3M5

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Major article
Published: 25 July 2021 in American Journal of Infection Control
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Background The COVID-19 pandemic highlighted the need for evidence-based approaches to decontamination and reuse of N95 filtering facepiece respirators (FFRs). We sought to determine whether vapourized hydrogen peroxide (VHP) reduced SARS-CoV-2 bioburden on FFRs without compromising filtration efficiency. We also investigated coronavirus HCoV-229E as a surrogate for decontamination validation testing. Methods N95 FFRs were laced with SARS-CoV-2 or HCoV-229E and treated with VHP in a hospital reprocessing facility. After sterilization, viral burden was determined using viral outgrowth in a titration assay, and filtration efficiency of FFRs was tested against ATSM F2299 and NIOSH TEB-STP-APR-0059. Results Viable SARS-CoV-2 virus was not detected after VHP treatment. One replicate of the HCoV-229E laced FFRs yielded virus after processing. Unexpired N95 FFRs retained full filtration efficiency after VHP processing. Expired FFRs failed to meet design-specified filtration efficiency and therefore are unsuitable for reprocessing. Discussion In-hospital VHP is an effective decontaminant for SARS-CoV-2 on FFRs. Further, filtration efficiency of unexpired respirators is not affected by this decontamination process. Conclusions VHP is effective in inactivating SARS-CoV-2 on FFRs without compromising filtration efficiency. HCoV-229E is a suitable surrogate for SARS-CoV-2 for disinfection studies.

ACS Style

Natasha Christie-Holmes; Rachel Tyli; Patrick Budylowski; Furkan Guvenc; Amit Weiner; Betty Poon; Mary Speck; Stephenie Naugler; Allen Rainville; Ayoob Ghalami; Shannon McCaw; Steven Hayes; Samira Mubareka; Scott D. Gray-Owen; Ori D. Rotstein; Rita A. Kandel; James A. Scott. Vapourized Hydrogen Peroxide Decontamination in a Hospital Setting Inactivates SARS-CoV-2 and HCoV-229E without Compromising Filtration Efficiency of Unexpired N95 Respirators. American Journal of Infection Control 2021, 1 .

AMA Style

Natasha Christie-Holmes, Rachel Tyli, Patrick Budylowski, Furkan Guvenc, Amit Weiner, Betty Poon, Mary Speck, Stephenie Naugler, Allen Rainville, Ayoob Ghalami, Shannon McCaw, Steven Hayes, Samira Mubareka, Scott D. Gray-Owen, Ori D. Rotstein, Rita A. Kandel, James A. Scott. Vapourized Hydrogen Peroxide Decontamination in a Hospital Setting Inactivates SARS-CoV-2 and HCoV-229E without Compromising Filtration Efficiency of Unexpired N95 Respirators. American Journal of Infection Control. 2021; ():1.

Chicago/Turabian Style

Natasha Christie-Holmes; Rachel Tyli; Patrick Budylowski; Furkan Guvenc; Amit Weiner; Betty Poon; Mary Speck; Stephenie Naugler; Allen Rainville; Ayoob Ghalami; Shannon McCaw; Steven Hayes; Samira Mubareka; Scott D. Gray-Owen; Ori D. Rotstein; Rita A. Kandel; James A. Scott. 2021. "Vapourized Hydrogen Peroxide Decontamination in a Hospital Setting Inactivates SARS-CoV-2 and HCoV-229E without Compromising Filtration Efficiency of Unexpired N95 Respirators." American Journal of Infection Control , no. : 1.

Preprint content
Published: 20 May 2021
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Background The aim of this prospective cohort study was to determine the burden of SARS-CoV-2 in air and on surfaces in rooms of patients hospitalized with COVID-19, and to identify patient characteristics associated with SARS-CoV-2 environmental contamination. Methods Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at six acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 viral RNA and cultured to determine potential infectivity. Whole viral genomes were sequenced from nasopharyngeal and surface samples. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated using a mixed-effects logistic regression model. Findings SARS-CoV-2 RNA was detected from surfaces (125/474 samples; 42/78 patients) and air (3/146 samples; 3/45 patients) in COVID-19 patient rooms; 14% (6/42) of surface samples from three patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, a PCR-positive nasopharyngeal swab with a cycle threshold of ≤30 on or after surface sampling date, higher Charlson co-morbidity score, and shorter time from onset of illness to sample date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. Interpretation The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited. Surface contamination was greater when patients were earlier in their course of illness and in those with hypoxia, multiple co-morbidities, and higher SARS-CoV-2 RNA concentration in NP swabs. Our results suggest that, while early detection and isolation of COVID-19 patients is important, air and surfaces may pose limited risk a few days after admission to acute care hospitals.

ACS Style

Jonathon D. Kotwa; Alainna J. Jamal; Hamza Mbareche; Lily Yip; Patryk Aftanas; Shiva Barati; Natalie G. Bell; Elizabeth Bryce; Eric D Coomes; Gloria Crowl; Caroline Duchaine; Amna Faheem; Lubna Farooqi; Ryan Hiebert; Kevin Katz; Saman Khan; Robert Kozak; Angel X. Li; Henna P. Mistry; Mohammad Mozafarihashjin; Jalees A. Nasir; Kuganya Nirmalarajah; Emily M. Panousis; Aimee Paterson; Simon Plenderleith; Jeff Powis; Karren Prost; Renee Schryer; Maureen Taylor; Marc Veillette; Titus Wong; Xi Zoe Zhong; Andrew G. McArthur; Allison J. McGeer; Samira Mubareka. Surface and air contamination with SARS-CoV-2 from hospitalized COVID-19 patients in Toronto, Canada. 2021, 1 .

AMA Style

Jonathon D. Kotwa, Alainna J. Jamal, Hamza Mbareche, Lily Yip, Patryk Aftanas, Shiva Barati, Natalie G. Bell, Elizabeth Bryce, Eric D Coomes, Gloria Crowl, Caroline Duchaine, Amna Faheem, Lubna Farooqi, Ryan Hiebert, Kevin Katz, Saman Khan, Robert Kozak, Angel X. Li, Henna P. Mistry, Mohammad Mozafarihashjin, Jalees A. Nasir, Kuganya Nirmalarajah, Emily M. Panousis, Aimee Paterson, Simon Plenderleith, Jeff Powis, Karren Prost, Renee Schryer, Maureen Taylor, Marc Veillette, Titus Wong, Xi Zoe Zhong, Andrew G. McArthur, Allison J. McGeer, Samira Mubareka. Surface and air contamination with SARS-CoV-2 from hospitalized COVID-19 patients in Toronto, Canada. . 2021; ():1.

Chicago/Turabian Style

Jonathon D. Kotwa; Alainna J. Jamal; Hamza Mbareche; Lily Yip; Patryk Aftanas; Shiva Barati; Natalie G. Bell; Elizabeth Bryce; Eric D Coomes; Gloria Crowl; Caroline Duchaine; Amna Faheem; Lubna Farooqi; Ryan Hiebert; Kevin Katz; Saman Khan; Robert Kozak; Angel X. Li; Henna P. Mistry; Mohammad Mozafarihashjin; Jalees A. Nasir; Kuganya Nirmalarajah; Emily M. Panousis; Aimee Paterson; Simon Plenderleith; Jeff Powis; Karren Prost; Renee Schryer; Maureen Taylor; Marc Veillette; Titus Wong; Xi Zoe Zhong; Andrew G. McArthur; Allison J. McGeer; Samira Mubareka. 2021. "Surface and air contamination with SARS-CoV-2 from hospitalized COVID-19 patients in Toronto, Canada." , no. : 1.

Preprint content
Published: 09 April 2021
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The COVID-19 pandemic has affected more than 120 million people and resulted in over 2.8 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all of the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Here, we describe intranasal immunization of a COVID-19 vaccine delivered by a novel platform, the helper-dependent adenoviral (HD-Ad) vector. Since HD-Ad vectors are devoid of adenoviral coding sequences, they have a superior safety profile and a large cloning capacity for transgenes. The vaccine (HD-Ad_RBD) codes for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and intranasal immunization induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. As such, intranasal immunization based on the HD-Ad vector promises to provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

ACS Style

Huibi Cao; Juntao Mai; Zhichang Zhou; Zhijie Li; Rongqi Duan; Jacqueline Watt; Ziyan Chen; Ranmal Avinash Bandara; Ming Li; Sang Kyun Ahn; Betty Boon; Natasha Christie; Scott Gray-Owen; Rob Kozak; Samira Mubareka; James M. Rini; Jim Hu; Jun Liu. Intranasal HD-Ad Vaccine Protects the Upper and Lower Respiratory Tracts of hACE2 Mice against SARS-CoV-2. 2021, 1 .

AMA Style

Huibi Cao, Juntao Mai, Zhichang Zhou, Zhijie Li, Rongqi Duan, Jacqueline Watt, Ziyan Chen, Ranmal Avinash Bandara, Ming Li, Sang Kyun Ahn, Betty Boon, Natasha Christie, Scott Gray-Owen, Rob Kozak, Samira Mubareka, James M. Rini, Jim Hu, Jun Liu. Intranasal HD-Ad Vaccine Protects the Upper and Lower Respiratory Tracts of hACE2 Mice against SARS-CoV-2. . 2021; ():1.

Chicago/Turabian Style

Huibi Cao; Juntao Mai; Zhichang Zhou; Zhijie Li; Rongqi Duan; Jacqueline Watt; Ziyan Chen; Ranmal Avinash Bandara; Ming Li; Sang Kyun Ahn; Betty Boon; Natasha Christie; Scott Gray-Owen; Rob Kozak; Samira Mubareka; James M. Rini; Jim Hu; Jun Liu. 2021. "Intranasal HD-Ad Vaccine Protects the Upper and Lower Respiratory Tracts of hACE2 Mice against SARS-CoV-2." , no. : 1.

Multicenter study
Published: 28 March 2021 in Canadian Medical Association Journal
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BACKGROUND: Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population. METHODS: We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza. RESULTS: Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0–7.0] days). Overall, 14.6% (12.4%–19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0–13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0–10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000–$16 000). INTERPRETATION: The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

ACS Style

Nelson Lee; Stephanie Smith; Nathan Zelyas; Scott Klarenbach; Lori Zapernick; Christian Bekking; Helen So; Lily Yip; Graham Tipples; Geoff Taylor; Samira Mubareka. Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres. Canadian Medical Association Journal 2021, 193, E439 -E446.

AMA Style

Nelson Lee, Stephanie Smith, Nathan Zelyas, Scott Klarenbach, Lori Zapernick, Christian Bekking, Helen So, Lily Yip, Graham Tipples, Geoff Taylor, Samira Mubareka. Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres. Canadian Medical Association Journal. 2021; 193 (13):E439-E446.

Chicago/Turabian Style

Nelson Lee; Stephanie Smith; Nathan Zelyas; Scott Klarenbach; Lori Zapernick; Christian Bekking; Helen So; Lily Yip; Graham Tipples; Geoff Taylor; Samira Mubareka. 2021. "Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres." Canadian Medical Association Journal 193, no. 13: E439-E446.

Journal article
Published: 02 February 2021 in Pathogens
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MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

ACS Style

Sreekumar Othumpangat; William Lindsley; Donald Beezhold; Michael Kashon; Carmen Burrell; Samira Mubareka; John Noti. Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons. Pathogens 2021, 10, 149 .

AMA Style

Sreekumar Othumpangat, William Lindsley, Donald Beezhold, Michael Kashon, Carmen Burrell, Samira Mubareka, John Noti. Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons. Pathogens. 2021; 10 (2):149.

Chicago/Turabian Style

Sreekumar Othumpangat; William Lindsley; Donald Beezhold; Michael Kashon; Carmen Burrell; Samira Mubareka; John Noti. 2021. "Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons." Pathogens 10, no. 2: 149.

Research article
Published: 08 October 2020 in Science Immunology
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Although the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) immunoglobulin G (IgG), IgA, and IgM responses to the SARS-CoV-2 spike protein (full-length trimer) and its receptor binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed coronavirus disease 2019 (COVID-19) ranging from 3 to 115 days postsymptom onset (PSO), compared with negative controls. Anti–SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16 to 30 days PSO. Longitudinal analysis revealed that anti–SARS-CoV-2 IgA and IgM antibodies rapidly decayed, whereas IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Last, IgG, IgM, and, to a lesser extent, IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in most of the patients with COVID-19 for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

ACS Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19. Science Immunology 2020, 5, eabe5511 .

AMA Style

Baweleta Isho, Kento T. Abe, Michelle Zuo, Alainna J. Jamal, Bhavisha Rathod, Jenny H. Wang, Zhijie Li, Gary Chao, Olga L. Rojas, Yeo Myong Bang, Annie Pu, Natasha Christie-Holmes, Christian Gervais, Derek Ceccarelli, Payman Samavarchi-Tehrani, Furkan Guvenc, Patrick Budylowski, Angel Li, Aimee Paterson, Yue Feng Yun, Lina M. Marin, Lauren Caldwell, Jeffrey L. Wrana, Karen Colwill, Frank Sicheri, Samira Mubareka, Scott D. Gray-Owen, Steven J. Drews, Walter L. Siqueira, Miriam Barrios-Rodiles, Mario Ostrowski, James M. Rini, Yves Durocher, Allison J. McGeer, Jennifer L. Gommerman, Anne-Claude Gingras. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19. Science Immunology. 2020; 5 (52):eabe5511.

Chicago/Turabian Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. 2020. "Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19." Science Immunology 5, no. 52: eabe5511.

Observational study
Published: 08 October 2020
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Saliva is an alternative biofluid to serum for detecting and monitoring IgG to SARS-CoV-2 spike and RBD antigens in COVID-19.

ACS Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Feng Yun Yue; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. 2020, 5, 1 .

AMA Style

Baweleta Isho, Kento T. Abe, Michelle Zuo, Alainna J. Jamal, Bhavisha Rathod, Jenny H. Wang, Zhijie Li, Gary Chao, Olga L. Rojas, Yeo Myong Bang, Annie Pu, Natasha Christie-Holmes, Christian Gervais, Derek Ceccarelli, Payman Samavarchi-Tehrani, Furkan Guvenc, Patrick Budylowski, Angel Li, Aimee Paterson, Feng Yun Yue, Lina M. Marin, Lauren Caldwell, Jeffrey L. Wrana, Karen Colwill, Frank Sicheri, Samira Mubareka, Scott D. Gray-Owen, Steven J. Drews, Walter L. Siqueira, Miriam Barrios-Rodiles, Mario Ostrowski, James M. Rini, Yves Durocher, Allison J. McGeer, Jennifer L. Gommerman, Anne-Claude Gingras. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. . 2020; 5 (52):1.

Chicago/Turabian Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Feng Yun Yue; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. 2020. "Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients." 5, no. 52: 1.

Journal article
Published: 02 October 2020 in JCI Insight
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Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin converting-enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of two viral based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus, and a spike pseudotyped viral-vector-based assay.

ACS Style

Kento T. Abe; Zhijie Li; Reuben Samson; Payman Samavarchi-Tehrani; Emelissa J. Valcourt; Heidi Wood; Patrick Budylowski; Alan P. Dupuis Ii; Roxie C. Girardin; Bhavisha Rathod; Jenny H. Wang; Miriam Barrios-Rodiles; Karen Colwill; Allison J. McGeer; Samira Mubareka; Jennifer L. Gommerman; Yves Durocher; Mario Ostrowski; Kathleen A. McDonough; Michael A. Drebot; Steven J. Drews; James M. Rini; Anne-Claude Gingras. A simple protein-based surrogate neutralization assay for SARS-CoV-2. JCI Insight 2020, 5, 1 .

AMA Style

Kento T. Abe, Zhijie Li, Reuben Samson, Payman Samavarchi-Tehrani, Emelissa J. Valcourt, Heidi Wood, Patrick Budylowski, Alan P. Dupuis Ii, Roxie C. Girardin, Bhavisha Rathod, Jenny H. Wang, Miriam Barrios-Rodiles, Karen Colwill, Allison J. McGeer, Samira Mubareka, Jennifer L. Gommerman, Yves Durocher, Mario Ostrowski, Kathleen A. McDonough, Michael A. Drebot, Steven J. Drews, James M. Rini, Anne-Claude Gingras. A simple protein-based surrogate neutralization assay for SARS-CoV-2. JCI Insight. 2020; 5 (19):1.

Chicago/Turabian Style

Kento T. Abe; Zhijie Li; Reuben Samson; Payman Samavarchi-Tehrani; Emelissa J. Valcourt; Heidi Wood; Patrick Budylowski; Alan P. Dupuis Ii; Roxie C. Girardin; Bhavisha Rathod; Jenny H. Wang; Miriam Barrios-Rodiles; Karen Colwill; Allison J. McGeer; Samira Mubareka; Jennifer L. Gommerman; Yves Durocher; Mario Ostrowski; Kathleen A. McDonough; Michael A. Drebot; Steven J. Drews; James M. Rini; Anne-Claude Gingras. 2020. "A simple protein-based surrogate neutralization assay for SARS-CoV-2." JCI Insight 5, no. 19: 1.

Other
Published: 01 September 2020
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There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-γ to TNF-α ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-γg+ CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.

ACS Style

Jaclyn C. Law; Wan Hon Koh; Patrick Budylowski; Jonah Lin; Fengyun Yue; Kento T. Abe; Bhavisha Rathod; Melanie Girard; Zhijie Li; James M. Rini; Samira Mubareka; Allison McGeer; Adrienne K. Chan; Anne-Claude Gingras; Tania H. Watts; Mario Ostrowski. Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile. 2020, 1 .

AMA Style

Jaclyn C. Law, Wan Hon Koh, Patrick Budylowski, Jonah Lin, Fengyun Yue, Kento T. Abe, Bhavisha Rathod, Melanie Girard, Zhijie Li, James M. Rini, Samira Mubareka, Allison McGeer, Adrienne K. Chan, Anne-Claude Gingras, Tania H. Watts, Mario Ostrowski. Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile. . 2020; ():1.

Chicago/Turabian Style

Jaclyn C. Law; Wan Hon Koh; Patrick Budylowski; Jonah Lin; Fengyun Yue; Kento T. Abe; Bhavisha Rathod; Melanie Girard; Zhijie Li; James M. Rini; Samira Mubareka; Allison McGeer; Adrienne K. Chan; Anne-Claude Gingras; Tania H. Watts; Mario Ostrowski. 2020. "Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile." , no. : 1.

Journal article
Published: 15 August 2020 in Viruses
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Genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly important to monitor the transmission and adaptive evolution of the virus. The accessibility of high-throughput methods and polymerase chain reaction (PCR) has facilitated a growing ecosystem of protocols. Two differing protocols are tiling multiplex PCR and bait capture enrichment. Each method has advantages and disadvantages but a direct comparison with different viral RNA concentrations has not been performed to assess the performance of these approaches. Here we compare Liverpool amplification, ARTIC amplification, and bait capture using clinical diagnostics samples. All libraries were sequenced using an Illumina MiniSeq with data analyzed using a standardized bioinformatics workflow (SARS-CoV-2 Illumina GeNome Assembly Line; SIGNAL). One sample showed poor SARS-CoV-2 genome coverage and consensus, reflective of low viral RNA concentration. In contrast, the second sample had a higher viral RNA concentration, which yielded good genome coverage and consensus. ARTIC amplification showed the highest depth of coverage results for both samples, suggesting this protocol is effective for low concentrations. Liverpool amplification provided a more even read coverage of the SARS-CoV-2 genome, but at a lower depth of coverage. Bait capture enrichment of SARS-CoV-2 cDNA provided results on par with amplification. While only two clinical samples were examined in this comparative analysis, both the Liverpool and ARTIC amplification methods showed differing efficacy for high and low concentration samples. In addition, amplification-free bait capture enriched sequencing of cDNA is a viable method for generating a SARS-CoV-2 genome sequence and for identification of amplification artifacts.

ACS Style

Jalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses 2020, 12, 895 .

AMA Style

Jalees A. Nasir, Robert A. Kozak, Patryk Aftanas, Amogelang R. Raphenya, Kendrick M. Smith, Finlay Maguire, Hassaan Maan, Muhannad Alruwaili, Arinjay Banerjee, Hamza Mbareche, Brian P. Alcock, Natalie C. Knox, Karen Mossman, Bo Wang, Julian A. Hiscox, Andrew G. McArthur, Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses. 2020; 12 (8):895.

Chicago/Turabian Style

Jalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. 2020. "A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture." Viruses 12, no. 8: 895.

Other
Published: 11 August 2020
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Objectives The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnea is challenging to assess remotely, and the accuracy of subjective dyspnea measures in capturing hypoxemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnea in diagnosing hypoxemia in COVID-19 patients. Methods This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from April 3, 2020 to June 8, 2020. Hypoxemia was defined by oxygen saturation Results During the study period 64/298 (21.5%) of patients met criteria for home oxygen saturation monitoring, and of these 14/64 (21.9%) were diagnosed with hypoxemia. The presence/absence of dyspnea had limited accuracy for diagnosing hypoxemia, with SN 57% (95% CI 30-81%), SP 78% (63%-88%), NPV 86% (72%-94%), PPV 42% (21%-66%), +LR 2.55 (1.3-5.1), -LR 0.55 (0.3-1.0). An mMRC dyspnea score >1 (SP 97%, 95%CI 82%-100%), Roth Maximal Count Conclusions Subjective dyspnea measures have inadequate accuracy for ruling out hypoxemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.

ACS Style

Linor Berezin; Alice Zhabokritsky; Nisha Andany; Adrienne K. Chan; Andrea Gershon; Philip W. Lam; Jerome A. Leis; Scott Macphee; Samira Mubareka; Andrew E. Simor; Nick Daneman. The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19. 2020, 1 .

AMA Style

Linor Berezin, Alice Zhabokritsky, Nisha Andany, Adrienne K. Chan, Andrea Gershon, Philip W. Lam, Jerome A. Leis, Scott Macphee, Samira Mubareka, Andrew E. Simor, Nick Daneman. The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19. . 2020; ():1.

Chicago/Turabian Style

Linor Berezin; Alice Zhabokritsky; Nisha Andany; Adrienne K. Chan; Andrea Gershon; Philip W. Lam; Jerome A. Leis; Scott Macphee; Samira Mubareka; Andrew E. Simor; Nick Daneman. 2020. "The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19." , no. : 1.

Other
Published: 04 August 2020
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While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31–45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105–115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity. One Sentence Summary In this manuscript, we report evidence for sustained SARS-CoV-2-specific IgG and transient IgA and IgM responses both at the site of infection (mucosae) and systemically in COVID-19 patients over 3 months and suggest that saliva could be used as an alternative biofluid for monitoring IgG to SARS-CoV-2 spike and RBD antigens.

ACS Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients. 2020, 1 .

AMA Style

Baweleta Isho, Kento T. Abe, Michelle Zuo, Alainna J. Jamal, Bhavisha Rathod, Jenny H. Wang, Zhijie Li, Gary Chao, Olga L. Rojas, Yeo Myong Bang, Annie Pu, Natasha Christie-Holmes, Christian Gervais, Derek Ceccarelli, Payman Samavarchi-Tehrani, Furkan Guvenc, Patrick Budylowski, Angel Li, Aimee Paterson, Yue Feng Yun, Lina M. Marin, Lauren Caldwell, Jeffrey L. Wrana, Karen Colwill, Frank Sicheri, Samira Mubareka, Scott D. Gray-Owen, Steven J. Drews, Walter L. Siqueira, Miriam Barrios-Rodiles, Mario Ostrowski, James M. Rini, Yves Durocher, Allison J. McGeer, Jennifer L. Gommerman, Anne-Claude Gingras. Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients. . 2020; ():1.

Chicago/Turabian Style

Baweleta Isho; Kento T. Abe; Michelle Zuo; Alainna J. Jamal; Bhavisha Rathod; Jenny H. Wang; Zhijie Li; Gary Chao; Olga L. Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M. Marin; Lauren Caldwell; Jeffrey L. Wrana; Karen Colwill; Frank Sicheri; Samira Mubareka; Scott D. Gray-Owen; Steven J. Drews; Walter L. Siqueira; Miriam Barrios-Rodiles; Mario Ostrowski; James M. Rini; Yves Durocher; Allison J. McGeer; Jennifer L. Gommerman; Anne-Claude Gingras. 2020. "Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients." , no. : 1.

Journal article
Published: 21 July 2020 in Chest
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Background During medical procedures with the potential to produce aerosols such as bronchoscopy, intubation, or CPR, health-care workers (HCWs) may be exposed to infectious bioaerosols. This scenario is of particular concern when high consequence pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are circulating. Thousands of HCWs have been infected with SARS-CoV-2. However, the determinants of aerosol generation during medical procedures and their relative risk to HCWs remain poorly characterized. Research Question The goal of this study was to characterize aerosols produced during airway intubation by using an uninfected translational animal model and in human subjects undergoing elective aerosol-generating procedures. The study also determined the particle size distribution of generated particles. Study Design and Methods Aerosol generation was measured during highly controlled experimental (pig) intubations (N = 16) and elective bronchoscopies in uninfected patients (N = 49) using an optical particle counter. Recovery of normal respiratory flora was used as a surrogate for pathogen dispersion. Results There was a small but significant (P = .03) decrease in 0.3 μm size particles during highly controlled pig intubations compared with baseline. The concentration of 1.0 μm and 5.0 μm aerosol particles did not significantly change, although oral bacteria were collected from the air. For elective patient bronchoscopies, there was a significant decrease in the generation of larger particles (1.0 μm and 5.0 μm) compared with baseline (P < .01); however, 18 of 39 (46%) patients showed increased aerosol production in 0.3 μm size particles, four of whom exhibited measurable increases. Interpretation Although the total amount of aerosols produced during intubation and bronchoscopy did not increase significantly relative to preprocedural levels, a small number of participants exhibited a measurable increase in submicron particle emission, meriting further research to delineate determinants of fine particle production during aerosol-generating procedures.

ACS Style

Nathan Doggett; Chung-Wai Chow; Samira Mubareka. Characterization of Experimental and Clinical Bioaerosol Generation During Potential Aerosol-Generating Procedures. Chest 2020, 158, 2467 -2473.

AMA Style

Nathan Doggett, Chung-Wai Chow, Samira Mubareka. Characterization of Experimental and Clinical Bioaerosol Generation During Potential Aerosol-Generating Procedures. Chest. 2020; 158 (6):2467-2473.

Chicago/Turabian Style

Nathan Doggett; Chung-Wai Chow; Samira Mubareka. 2020. "Characterization of Experimental and Clinical Bioaerosol Generation During Potential Aerosol-Generating Procedures." Chest 158, no. 6: 2467-2473.

Letter
Published: 14 July 2020 in Trials
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Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, number of days unable to work attributed to COVID-19, seroconversion (COVID-19 negative to COVID-19 positive over the study period); ability of participant plasma to neutralize SARS-CoV-2 virus in vitro; To describe short-term psychological distress associated with risk of COVID-19 exposure at 1, 60, 120 days of the study. To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure. At 90 days, there is an open label extension wherein all participants are offered a one-month course of HCQ 400mg once daily for PrEP of COVID-19. Frontline HCWs aged 18 years of age or older, at high risk of SARS-CoV-2 exposure (including staff of emergency departments, intensive care units, intubation teams, COVID-wards, and staff deployed to Long Term Care facilities) of five academic hospitals in downtown Toronto, Canada. Exclusion criteria include: currently pregnant, planning to become pregnant during the study period, and/or breast feeding; known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds; current use of hydroxychloroquine; known prolonged QT syndrome and/or baseline resting ECG with QTc>450 ms and/or concomitant medications which simultaneously may prolong the QTc that cannot be temporarily suspended/replaced; known pre-existing retinopathy, G6PD deficiency, porphyria, liver disease including cirrhosis, encephalopathy, hepatitis or alcoholism, diabetes on oral hypoglycemics or insulin, or renal insufficiency/failure; disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study; confirmed symptomatic COVID-19 at time of enrollment. Intervention: hydroxychloroquine, 400mg (2 tablets) orally per day. Comparator: placebo, two tablets visually identical to the intervention, orally per day The primary outcome is microbiologically confirmed COVID-19 (i.e. SARS-CoV-2 infection). This is a composite endpoint which includes positive results from any validated SARS-CoV-2 diagnostic assay including detection of viral RNA, and/or seroconversion. Participants will be assessed at baseline, and then undergo monthly follow-up at day 30, 60, and 90, 120. At each visit, participants will provide an oropharyngeal sample, blood sample, and will undergo electrocardiogram monitoring of the QTc interval. Secondary outcome measures include: adverse events; symptom duration of COVID-19; days of hospitalization attributed to COVID-19; respiratory failure requiring ventilator support attributed to COVID-19; mortality attributed to COVID-19; total days off work attributed to COVID-19; seropositivity (reactive serology by day 120); and short term psychological impact of exposure to SARS-CoV-2 at day 1, 60, 120 days using the K10, a validated measure of non-specific psychological distress. Within each site, participants will be individually randomized to either the intervention arm with HCQ or the placebo arm using a fixed 1:1 allocation ratio using an interactive web-based response system to ensure concealment of allocation. Randomization schedules will be computer-generated and blocked using variable block sizes. All participants, research coordinators, technicians, clinicians and investigators will be blinded to the participant allocation group. Numbers to be randomised (sample size) N=988, randomised into two groups of 494 patients. This summary describes protocol version No. 1.6, May 15, 2020. Recruitment is ongoing - started April 20, 2020 and anticipated end date is July 30, 2021 ISRCTN.com Identifier: ISRCTN14326006, registered April 14, 2020. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

ACS Style

Julie K. Wright; Darrell H. S. Tan; Sharon L. Walmsley; Jennifer Hulme; Erin O’Connor; Carolyn Snider; Ivy Cheng; Adrienne K. Chan; Bjug Borgundvaag; Shelley McLeod; Michael H. Gollob; Rosemarie J. Clarke; Linda Dresser; Fatima Haji; Tony Mazzulli; Samira Mubareka; Peter Jüni; Dominic Lee; George Tomlinson; Kevin C. Kain; Megan Landes. Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada. Trials 2020, 21, 1 -3.

AMA Style

Julie K. Wright, Darrell H. S. Tan, Sharon L. Walmsley, Jennifer Hulme, Erin O’Connor, Carolyn Snider, Ivy Cheng, Adrienne K. Chan, Bjug Borgundvaag, Shelley McLeod, Michael H. Gollob, Rosemarie J. Clarke, Linda Dresser, Fatima Haji, Tony Mazzulli, Samira Mubareka, Peter Jüni, Dominic Lee, George Tomlinson, Kevin C. Kain, Megan Landes. Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada. Trials. 2020; 21 (1):1-3.

Chicago/Turabian Style

Julie K. Wright; Darrell H. S. Tan; Sharon L. Walmsley; Jennifer Hulme; Erin O’Connor; Carolyn Snider; Ivy Cheng; Adrienne K. Chan; Bjug Borgundvaag; Shelley McLeod; Michael H. Gollob; Rosemarie J. Clarke; Linda Dresser; Fatima Haji; Tony Mazzulli; Samira Mubareka; Peter Jüni; Dominic Lee; George Tomlinson; Kevin C. Kain; Megan Landes. 2020. "Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada." Trials 21, no. 1: 1-3.

Preprint content
Published: 11 July 2020
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Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin converting-enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of two viral based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus, and a spike pseudotyped viral-vector-based assay.

ACS Style

Kento T. Abe; Zhijie Li; Reuben Samson; Payman Samavarchi-Tehrani; Emelissa J. Valcourt; Heidi Wood; Patrick Budylowski; Alan P. Dupuis; Roxie C. Girardin; Bhavisha Rathod; Jenny H. Wang; Miriam Barrios-Rodiles; Karen Colwill; Allison J McGeer; Samira Mubareka; Jennifer L. Gommerman; Yves Durocher; Mario A Ostrowski; Kathleen A. McDonough; Michael A. Drebot; Steven J. Drews; James M. Rini; Anne-Claude Gingras. A simple protein-based surrogate neutralization assay for SARS-CoV-2. 2020, 1 .

AMA Style

Kento T. Abe, Zhijie Li, Reuben Samson, Payman Samavarchi-Tehrani, Emelissa J. Valcourt, Heidi Wood, Patrick Budylowski, Alan P. Dupuis, Roxie C. Girardin, Bhavisha Rathod, Jenny H. Wang, Miriam Barrios-Rodiles, Karen Colwill, Allison J McGeer, Samira Mubareka, Jennifer L. Gommerman, Yves Durocher, Mario A Ostrowski, Kathleen A. McDonough, Michael A. Drebot, Steven J. Drews, James M. Rini, Anne-Claude Gingras. A simple protein-based surrogate neutralization assay for SARS-CoV-2. . 2020; ():1.

Chicago/Turabian Style

Kento T. Abe; Zhijie Li; Reuben Samson; Payman Samavarchi-Tehrani; Emelissa J. Valcourt; Heidi Wood; Patrick Budylowski; Alan P. Dupuis; Roxie C. Girardin; Bhavisha Rathod; Jenny H. Wang; Miriam Barrios-Rodiles; Karen Colwill; Allison J McGeer; Samira Mubareka; Jennifer L. Gommerman; Yves Durocher; Mario A Ostrowski; Kathleen A. McDonough; Michael A. Drebot; Steven J. Drews; James M. Rini; Anne-Claude Gingras. 2020. "A simple protein-based surrogate neutralization assay for SARS-CoV-2." , no. : 1.

Preprint content
Published: 18 June 2020
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SUMMARY Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are lacking. Here we demonstrate that SARS-CoV-2 infection induces a mild type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Our data demonstrate that SARS-CoV-2 is not adept in blocking type I IFN responses and provide support for ongoing IFN clinical trials.

ACS Style

Arinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Kaushal Baid; Michael R. D’Agostino; Jann Catherine Ang; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario A Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. 2020, 1 .

AMA Style

Arinjay Banerjee, Nader El-Sayes, Patrick Budylowski, Daniel Richard, Hassaan Maan, Jennifer A. Aguiar, Kaushal Baid, Michael R. D’Agostino, Jann Catherine Ang, Benjamin J.-M. Tremblay, Sam Afkhami, Mehran Karimzadeh, Aaron T. Irving, Lily Yip, Mario A Ostrowski, Jeremy A. Hirota, Robert Kozak, Terence D. Capellini, Matthew S. Miller, Bo Wang, Samira Mubareka, Allison J. McGeer, Andrew G. McArthur, Andrew C. Doxey, Karen Mossman. Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses. . 2020; ():1.

Chicago/Turabian Style

Arinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer A. Aguiar; Kaushal Baid; Michael R. D’Agostino; Jann Catherine Ang; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario A Ostrowski; Jeremy A. Hirota; Robert Kozak; Terence D. Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G. McArthur; Andrew C. Doxey; Karen Mossman. 2020. "Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses." , no. : 1.

Other
Published: 05 May 2020
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We enrolled 53 consecutive in-patients with COVID-19 at six hospitals in Toronto, Canada, and tested one nasopharyngeal swab/saliva sample pair from each patient for SARS-CoV-2. Overall, sensitivity was 89% for nasopharyngeal swabs and 77% for saliva (p=NS); difference in sensitivity was greatest for sample pairs collected later in illness.

ACS Style

Alainna J. Jamal; Mohammad Mohammad; Eric Coomes; Jeff Powis; Angel Xin Liu; Aimee Paterson; Sofia Anceva-Sami; Shiva Barati; Gloria Crowl; Amna Faheem; Lubna Farooqi; Saman Khan; Karren Prost; Susan Poutanen; Lily Yip; Zoe Zhong; Allison J. McGeer; Samira Mubareka. Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2020, 1 .

AMA Style

Alainna J. Jamal, Mohammad Mohammad, Eric Coomes, Jeff Powis, Angel Xin Liu, Aimee Paterson, Sofia Anceva-Sami, Shiva Barati, Gloria Crowl, Amna Faheem, Lubna Farooqi, Saman Khan, Karren Prost, Susan Poutanen, Lily Yip, Zoe Zhong, Allison J. McGeer, Samira Mubareka. Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). . 2020; ():1.

Chicago/Turabian Style

Alainna J. Jamal; Mohammad Mohammad; Eric Coomes; Jeff Powis; Angel Xin Liu; Aimee Paterson; Sofia Anceva-Sami; Shiva Barati; Gloria Crowl; Amna Faheem; Lubna Farooqi; Saman Khan; Karren Prost; Susan Poutanen; Lily Yip; Zoe Zhong; Allison J. McGeer; Samira Mubareka. 2020. "Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." , no. : 1.

Preprint content
Published: 12 April 2020
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SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 100,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the evolution of the virus and the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two COVID-19 patients in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we have tested a wide range of human immune cells for infectivity with SARS-CoV-2. We confirm from our studies that human primary peripheral blood mononuclear cells (PBMCs) are not permissive to SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor any small nucleotide polymorphisms in the virus and to continue to isolate circulating strains of the virus to determine cell susceptibility and pathogenicity using in vitro and in vivo infection models.

ACS Style

Arinjay Banerjee; Jalees A. Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A Hirota; Matthew S. Miller; Allison J McGeer; Mario A Ostrowski; Robert A. Kozak; Andrew G McArthur; Karen Mossman; Samira Mubareka. Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2. 2020, 1 .

AMA Style

Arinjay Banerjee, Jalees A. Nasir, Patrick Budylowski, Lily Yip, Patryk Aftanas, Natasha Christie, Ayoob Ghalami, Kaushal Baid, Amogelang R. Raphenya, Jeremy A Hirota, Matthew S. Miller, Allison J McGeer, Mario A Ostrowski, Robert A. Kozak, Andrew G McArthur, Karen Mossman, Samira Mubareka. Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2. . 2020; ():1.

Chicago/Turabian Style

Arinjay Banerjee; Jalees A. Nasir; Patrick Budylowski; Lily Yip; Patryk Aftanas; Natasha Christie; Ayoob Ghalami; Kaushal Baid; Amogelang R. Raphenya; Jeremy A Hirota; Matthew S. Miller; Allison J McGeer; Mario A Ostrowski; Robert A. Kozak; Andrew G McArthur; Karen Mossman; Samira Mubareka. 2020. "Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2." , no. : 1.

Journal article
Published: 29 March 2020 in Journal of Clinical Virology
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The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality. The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity. A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality. CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death. This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.

ACS Style

Robert Kozak; Karren Prost; Lily Yip; Victoria Williams; Jerome A. Leis; Samira Mubareka. Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario. Journal of Clinical Virology 2020, 126, 104338 -104338.

AMA Style

Robert Kozak, Karren Prost, Lily Yip, Victoria Williams, Jerome A. Leis, Samira Mubareka. Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario. Journal of Clinical Virology. 2020; 126 ():104338-104338.

Chicago/Turabian Style

Robert Kozak; Karren Prost; Lily Yip; Victoria Williams; Jerome A. Leis; Samira Mubareka. 2020. "Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario." Journal of Clinical Virology 126, no. : 104338-104338.

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Published: 29 November 2019
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BackgroundRising rates of antibiotic resistance have led to the use of broader spectrum antibiotics and increasingly compromise empiric therapy. Knowing the antibiotic susceptibility of a pathogen’s close genetic relative(s) may improve empiric antibiotic selection.MethodsUsing genomic and phenotypic data from three separate clinically-derived databases of Escherichia coli isolates, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information such as lineage or genetic distance from archived isolates. We applied these methods to derive and validate prediction of antibiotic susceptibility to common antibiotics.ResultsWe evaluated 968 separate episodes of suspected and confirmed infection with Escherichia coli from three geographically and temporally separated databases in Ontario, Canada, from 2010-2018. The most common sequence type (ST) was ST131 (30%). Antibiotic susceptibility to ciprofloxacin and trimethoprim-sulfamethoxazole were lowest (<=72%). Across all approaches, model performance (AUC) ranges for predicting antibiotic susceptibility were greatest for ciprofloxacin (0.76-0.97), and lowest for trimethoprim-sulfamethoxazole (0.51-0.80). When a model predicted a susceptible isolate, the resulting (post-test) probabilities of susceptibility were sufficient to warrant empiric therapy for most antibiotics (mean 92%). An approach combining multiple models could permit the use of narrower spectrum oral agents in 2 out of every 3 patients while maintaining high treatment adequacy (∼90%).ConclusionsMethods based on genetic relatedness to archived samples in E. coli could be used to rescue older and typically unsuitable agents for use as empiric antibiotic therapy, as well as improve decisions to select newer broader spectrum agents.SummaryRapid genomic approaches that capitalize on the association between genetic relatedness and phenotype can improve our selection of antibiotics, allowing us to rescue older drugs for empiric use and better select newer and broader spectrum agents.

ACS Style

Derek R MacFadden; Bryan Coburn; Karel Břinda; Antoine Corbeil; Nick Daneman; David Fisman; Robyn S Lee; Marc Lipsitch; Allison McGeer; Roberto G. Melano; Samira Mubareka; William P Hanage. Using the Association Between Antibiotic Susceptibility and Genetic Relatedness to Rescue Old Drugs for Empiric Use. 2019, 19006106 .

AMA Style

Derek R MacFadden, Bryan Coburn, Karel Břinda, Antoine Corbeil, Nick Daneman, David Fisman, Robyn S Lee, Marc Lipsitch, Allison McGeer, Roberto G. Melano, Samira Mubareka, William P Hanage. Using the Association Between Antibiotic Susceptibility and Genetic Relatedness to Rescue Old Drugs for Empiric Use. . 2019; ():19006106.

Chicago/Turabian Style

Derek R MacFadden; Bryan Coburn; Karel Břinda; Antoine Corbeil; Nick Daneman; David Fisman; Robyn S Lee; Marc Lipsitch; Allison McGeer; Roberto G. Melano; Samira Mubareka; William P Hanage. 2019. "Using the Association Between Antibiotic Susceptibility and Genetic Relatedness to Rescue Old Drugs for Empiric Use." , no. : 19006106.