Immunogenicity and safety of mixed COVID-19 vaccine regimens in patients with immune-mediated inflammatory diseases: a single-centre prospective cohort study.

OBJECTIVE: Among persons with immune-mediated inflammatory diseases (IMIDs) who received SARS-CoV-2 vaccines, we compared postvaccine antibody responses and IMID disease activity/states. DESIGN: Single-centre prospective cohort study. SETTING: Specialty ambulatory clinics in central Canada. PARTICIPANTS: People with inflammatory arthritis (n=78; 77% rheumatoid arthritis), systemic autoimmune rheumatic diseases (n=84; 57% lupus), inflammatory bowel disease (n=93; 43% Crohn's) and multiple sclerosis (n=72; 71% relapsing-remitting) (female 79.4%, white 84.7%, mean (SD) age 56.0 (14.3) years) received COVID-19 vaccinations between March 2021 and September 2022. PRIMARY OUTCOME: Postvaccination anti-spike, anti-receptor binding domain (anti-RBD) and anti-nucleocapsid (anti-NC) IgG antibodies tested by multiplex immunoassays compared across vaccine regimens and with responses in 370 age-matched and sex-matched vaccinated controls. SECONDARY OUTCOMES: COVID-19 infection and self-reported IMID disease activity/state. RESULTS: Most (216/327, 66.1%) received homologous messenger RNA (mRNA) (BNT162b2 or mRNA1273) vaccines, 2.4% received homologous ChAdOx1 and 30.6% received heterologous vaccines (23.9% ChAdOx1/mRNA, 6.4% heterologous mRNA) for their first two vaccines (V1, V2). Seroconversion rates were 52.0% (91/175) for post-V1 anti-spike and 58.9% (103/175) for anti-RBD; 91.5% (214/234) for post-V2 anti-spike and 90.2% (211/234) for anti-RBD; and were lower than controls (post-V2 anti-spike 98.1% (360/370), p<0.0001). Antibody titres decreased 3 months after V2 but increased 1 month after the third vaccine (V3) and 1 month after the fourth vaccine (V4) (BAU/mL median (IQR), anti-spike 1835 (2448) 1 month post-V2, 629.1 (883.4) 3 months post-V2, 4757.5 (7033.1) 1 month post-V3 and 4356.0 (9393.4) 1 month post-V4; anti-RBD 1686.8 (2199.44) 1 month post-V2, 555.8 (809.3) 3 months post-V2, 4280.3 (6380.6) 1 month post-V3 and 4792.2 (11 673.78) 1 month post-V4). If primed with a vector vaccine, an mRNA vaccine increased antibody titres to those comparable to homologous mRNA vaccines. Anti-RBD and anti-spike titres were higher in anti-NC seropositive (n=31; 25 participants) versus seronegative samples (BAU/mL median (IQR) anti-RBD 11 755.3 (20 373.1) vs 1248.0 (53 278.7); anti-spike 11 254.4 (15 352.6) vs 1313.1 (3106.6); both p<0.001). IMID disease activity/state and rates of self-reported moderate or severe IMID flare were similar across vaccinations. CONCLUSION: Heterologous COVID-19 vaccination improves seroconversion rates following a vector vaccine and does not lead to IMID disease flare. IMIDs benefit from at least three vaccines.

Brain MRI Findings of Hemophagocytic Lymphohistiocytosis With a Heterozygous PRF1 Gene Mutation Masquerading As CLIPPERS: A Case Report.

Familial hemophagocytic lymphohistiocytosis is a rare and potentially life-threatening genetic condition characterized by unsuppressed immune activation and hypercytokinemia. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a central nervous system inflammatory disorder characterized by punctate and curvilinear gadolinium-enhancing lesions in the brainstem, cerebellum, and spinal cord, which responds well to corticosteroid treatment. Hemophagocytic lymphohistiocytosis has been known to mimic CLIPPERS on neuroimaging, and patients previously diagnosed with CLIPPERS may carry familial hemophagocytic lymphohistiocytosis-related gene mutations that serve as predisposing factors. In this article, we describe a case initially diagnosed with CLIPPERS based on characteristic magnetic resonance imaging features and clinical course, who was later diagnosed with hemophagocytic lymphohistiocytosis based on a heterozygous familial hemophagocytic lymphohistiocytosis-associated PRF1 gene mutation.

Neurological and Neuroradiological Manifestations in Neonates Born to Mothers With Coronavirus Disease 2019.

BACKGROUND: To investigate the complications that occurred in neonates born to mothers with coronavirus disease 2019 (COVID-19), focusing on neurological and neuroradiological findings, and to compare differences associated with the presence of maternal symptoms. METHODS: Ninety neonates from 88 mothers diagnosed with coronavirus disease 2019 (COVID-19) during pregnancy were retrospectively reviewed. Neonates were divided into two groups: symptomatic (Sym-M-N, n = 34) and asymptomatic mothers (Asym-M-N, n = 56). The results of neurological physical examinations were compared between the groups. Data on electroencephalography, brain ultrasound, and magnetic resonance imaging abnormalities were collected for neonates with neurological abnormalities. RESULTS: Neurological abnormalities at birth were found in nine neonates (Sym-M-N, seven of 34, 20.6%). Decreased tone was the most common physical abnormality (n = 7). Preterm and very preterm birth (P < 0.01), very low birth weight (P < 0.01), or at least one neurological abnormality on physical examination (P = 0.049) was more frequent in Sym-M-N neonates. All infants with abnormalities on physical examination showed neuroradiological abnormalities. The most common neuroradiological abnormalities were intracranial hemorrhage (n = 5; germinal matrix, n = 2; parenchymal, n = 2; intraventricular, n = 1) and hypoxic brain injury (n = 3). CONCLUSIONS: Neonates born to mothers with symptomatic COVID-19 showed an increased incidence of neurological abnormalities. Most of the mothers (96.4%) were unvaccinated before the COVID-19 diagnosis. Our results highlight the importance of neurological and neuroradiological management in infants born to mothers with COVID-19 and the prevention of maternal COVID-19 infection.

The Collateral Impact of the COVID-19 Pandemic on HPV-positive Oropharyngeal Cancer Diagnosis

Purpose We aim to assess the potential impact of the COVID-19 pandemic on diagnostic delays in HPV-positive oropharyngeal cancer (OPC), and to describe their underlying reasons. Methods All HPV+ OPC referred to a tertiary cancer centre and diagnosed between June-December 2019 (Pre-Pandemic cohort) vs June-December 2020 (Pandemic cohort) were reviewed. TNM classification, gross-tumor-volumes (GTV) and intervals between sign/symptom onset and treatment initiation were compared between the cohorts. Reasons for delay (>6 months from onset of signs/symptoms to a positive biopsy of the primary tumor, or a delay specifically mentioned in the patient chart) in establishing the diagnosis were recorded per clinician's documentation, and categorized as COVID-related or non-COVID-related. Results A total of 157 consecutive HPV+ OPC patients were identified (Pre-Pandemic: 92;Pandemic: 65). Compared to the Pre-Pandemic cohort, Pandemic cohort patients had a higher proportion of N2-N3 (32% vs 15%, p=0.019) and stage III (38% vs 23%, p=0.034) disease at presentation. The differences in proportions with >6 months delay from symptom onset to establishing the diagnosis (29% vs 20%, p=0.16) or to first treatment (49% vs 38%, p=0.22) were not statistically different. 47% of diagnostic delays in the Pandemic cohort were potentially attributable to COVID-19. Conclusion We observed a collateral impact of the COVID-19 pandemic on HPV+ OPC care through more advanced stage at presentation and a non-significant but numerically longer interval to diagnosis. This could adversely impact patient outcomes and future resource allocation. Both COVID-19-related or unrelated factors contribute to diagnostic delay. Tailored interventions to reduce delays are warranted.

The collateral impact of the COVID-19 pandemic on HPV-positive oropharyngeal cancer diagnosis.

PURPOSE: We aim to assess the potential impact of the COVID-19 pandemic on diagnostic delays in HPV-positive oropharyngeal cancer (OPC), and to describe their underlying reasons. METHODS: All HPV + OPC referred to a tertiary cancer centre and diagnosed between June-December 2019 (Pre-Pandemic cohort) vs June-December 2020 (Pandemic cohort) were reviewed. TNM classification, gross-tumor-volumes (GTV) and intervals between sign/symptom onset and treatment initiation were compared between the cohorts. Reasons for delay (>6 months from onset of signs/symptoms to a positive biopsy of the primary tumor, or a delay specifically mentioned in the patient chart) in establishing the diagnosis were recorded per clinician's documentation, and categorized as COVID-related or non-COVID-related. RESULTS: A total of 157 consecutive HPV + OPC patients were identified (Pre-Pandemic: 92; Pandemic: 65). Compared to the Pre-Pandemic cohort, Pandemic cohort patients had a higher proportion of N2-N3 (32 % vs 15 %, p = 0.019) and stage III (38 % vs 23 %, p = 0.034) disease at presentation. The differences in proportions with > 6 months delay from symptom onset to establishing the diagnosis (29 % vs 20 %, p = 0.16) or to first treatment (49 % vs 38 %, p = 0.22) were not statistically different. 47 % of diagnostic delays in the Pandemic cohort were potentially attributable to COVID-19. CONCLUSION: We observed a collateral impact of the COVID-19 pandemic on HPV + OPC care through more advanced stage at presentation and a non-significant but numerically longer interval to diagnosis. This could adversely impact patient outcomes and future resource allocation. Both COVID-19-related and unrelated factors contribute to diagnostic delays. Tailored interventions to reduce delays are warranted.

Deadly Fungi: Invasive Fungal Rhinosinusitis in the Head and Neck.

Invasive fungal rhinosinusitis (IFRS) is a serious infection that is associated with high morbidity and mortality rates. The incidence of IFRS has been increasing, mainly because of the increased use of antibiotics and immunosuppressive drugs. Rhino-orbital cerebral mucormycosis has recently reemerged among patients affected by COVID-19 and has become a global concern. The detection of extrasinus involvement in its early stage contributes to improved outcomes; therefore, imaging studies are essential in establishing the degree of involvement and managing the treatment properly, especially in immunocompromised patients. The common sites of extrasinus fungal invasion are the intraorbital, cavernous sinus, and intracranial regions. Fungi spread directly to these regions along the blood vessels or nerves, causing devastating complications such as optic nerve ischemia or compression, optic neuritis or perineuritis, orbital cellulitis, cavernous sinus thrombosis, mycotic aneurysm, vasculitis, internal carotid arterial occlusion, cerebral infarction, cerebritis, and brain abscess. IFRS has a broad imaging spectrum, and familiarity with intra- and extrasinonasal imaging features, such as loss of contrast enhancement of the affected region, which indicates tissue ischemia due to angioinvasion of fungi, and the surrounding anatomy is essential for prompt diagnosis and management. The authors summarize the epidemiology, etiology, risk factors, and complications of IFRS and review the anatomy and key diagnostic imaging features of IFRS beyond the sinonasal regions. ©RSNA, 2022.

Comparative performance data for multiplex SARS-CoV-2 serological assays from a large panel of dried blood spot specimens.

The extent of the COVID-19 pandemic will be better understood through serosurveys and SARS-CoV-2 antibody testing. Dried blood spot (DBS) samples will play a central role in large scale serosurveillance by simplifying biological specimen collection and transportation, especially in Canada. Direct comparative performance data on multiplex SARS-CoV-2 assays resulting from identical DBS samples are currently lacking. In our study, we aimed to provide performance data for the BioPlex 2200 SARS-CoV-2 IgG (Bio-Rad), V-PLEX SARS-CoV-2 Panel 2 IgG (MSD), and Elecsys Anti-SARS-CoV-2 (Roche) commercial assays, as well as for two highly scalable in-house assays (University of Ottawa and Mount Sinai Hospital protocols) to assess their suitability for DBS-based SARS-CoV-2 DBS serosurveillance. These assays were evaluated against identical panels of DBS samples collected from convalescent COVID-19 patients (n = 97) and individuals undergoing routine sexually transmitted and bloodborne infection (STBBI) testing prior to the COVID-19 pandemic (n = 90). Our findings suggest that several assays are suitable for serosurveillance (sensitivity >97% and specificity >98%). In contrast to other reports, we did not observe an improvement in performance using multiple antigen consensus-based rules to establish overall seropositivity. This may be due to our DBS panel which consisted of samples collected from convalescent COVID-19 patients with significant anti-spike, -receptor binding domain (RBD), and -nucleocapsid antibody titers. This study demonstrates that biological specimens collected as DBS coupled with one of several readily available assays are useful for large-scale COVID-19 serosurveillance.

Facial myonecrosis following COVID-19☆

Myositis and myonecrosis are rare sequela of coronavirus disease 2019 (COVID-19). Until now, it has not been seen in muscles of the head and neck. We present a 22-year-old male with 4 months of retroauricular headaches following COVID-19 infection. Magnetic resonance imaging revealed rim-enhancing fluid collections in the bilateral masticator spaces which were sampled by fine-needle aspiration. We also discuss this case in the context of the current understanding of COVID-19-related myositis.

Facial myonecrosis following COVID-19.

Myositis and myonecrosis are rare sequela of coronavirus disease 2019 (COVID-19). Until now, it has not been seen in muscles of the head and neck. We present a 22-year-old male with 4 months of retroauricular headaches following COVID-19 infection. Magnetic resonance imaging revealed rim-enhancing fluid collections in the bilateral masticator spaces which were sampled by fine-needle aspiration. We also discuss this case in the context of the current understanding of COVID-19-related myositis.

Designing a Framework for Remote Cancer Care Through Community Co-design: Participatory Development Study.

BACKGROUND: Recent shifts to telemedicine and remote patient monitoring demonstrate the potential for new technology to transform health systems; yet, methods to design for inclusion and resilience are lacking. OBJECTIVE: The aim of this study is to design and implement a participatory framework to produce effective health care solutions through co-design with diverse stakeholders. METHODS: We developed a design framework to cocreate solutions to locally prioritized health and communication problems focused on cancer care. The framework is premised on the framing and discovery of problems through community engagement and lead-user innovation with the hypothesis that diversity and inclusion in the co-design process generate more innovative and resilient solutions. Discovery, design, and development were implemented through structured phases with design studios at various locations in urban and rural Kentucky, including Appalachia, each building from prior work. In the final design studio, working prototypes were developed and tested. Outputs were assessed using the System Usability Scale as well as semistructured user feedback. RESULTS: We co-designed, developed, and tested a mobile app (myPath) and service model for distress surveillance and cancer care coordination following the LAUNCH (Linking and Amplifying User-Centered Networks through Connected Health) framework. The problem of awareness, navigation, and communication through cancer care was selected by the community after framing areas for opportunity based on significant geographic disparities in cancer and health burden resource and broadband access. The codeveloped digital myPath app showed the highest perceived combined usability (mean 81.9, SD 15.2) compared with the current gold standard of distress management for patients with cancer, the paper-based National Comprehensive Cancer Network Distress Thermometer (mean 74.2, SD 15.8). Testing of the System Usability Scale subscales showed that the myPath app had significantly better usability than the paper Distress Thermometer (t63=2.611; P=.01), whereas learnability did not differ between the instruments (t63=-0.311; P=.76). Notable differences by patient and provider scoring and feedback were found. CONCLUSIONS: Participatory problem definition and community-based co-design, design-with methods, may produce more acceptable and effective solutions than traditional design-for approaches.

Early warning and rapid public health response to prevent COVID-19 outbreaks in long-term care facilities (LTCF) by monitoring SARS-CoV-2 RNA in LTCF site-specific sewage samples and assessment of antibodies response in this population: prospective study protocol

IntroductionThe COVID-19 pandemic has an excessive impact on residents in long-term care facilities (LTCF), causing high morbidity and mortality. Early detection of presymptomatic and asymptomatic COVID-19 cases supports the timely implementation of effective outbreak control measures but repetitive screening of residents and staff incurs costs and discomfort. Administration of vaccines is key to controlling the pandemic but the robustness and longevity of the antibody response, correlation of neutralising antibodies with commercial antibody assays, and the efficacy of current vaccines for emerging COVID-19 variants require further study. We propose to monitor SARS-CoV-2 in site-specific sewage as an early warning system for COVID-19 in LTCF and to study the immune response of the staff and residents in LTCF to COVID-19 vaccines.Methods and analysisThe study includes two parts: (1) detection and quantification of SARS-CoV-2 in LTCF site-specific sewage samples using a molecular assay followed by notification of Public Health within 24 hours as an early warning system for appropriate outbreak investigation and control measures and cost–benefit analyses of the system and (2) testing for SARS-CoV-2 antibodies among staff and residents in LTCF at various time points before and after COVID-19 vaccination using commercial assays and neutralising antibody testing performed at a reference laboratory.Ethics and disseminationEthics approval was obtained from the University of Alberta Health Research Ethics Board with considerations to minimise risk and discomforts for the participants. Early recognition of a COVID-19 case in an LTCF might prevent further transmission in residents and staff. There was no direct benefit identified to the participants of the immunity study. Anticipated dissemination of information includes a summary report to the immunity study participants, sharing of study data with the scientific community through the Canadian COVID-19 Immunity Task Force, and prompt dissemination of study results in meeting s and manuscripts in peer-reviewed journals.

Study of the epidemiology of COVID-19 in Ontario elementary and secondary school education workers: an interim analysis following the first school year.

OBJECTIVE: To estimate the incidence of SARS-CoV-2 in education workers and the factors associated with infection between March 2020 and July 2021. METHODS: A prospective cohort study of education workers working ≥8 h per week in Ontario, Canada. Participants self-reported results of tests for SARS-CoV-2 and completed online surveys about demographic information, exposures, and vaccinations against SARS-CoV-2. Participants submitted self-collected dried blood spots. Antibodies to SARS-CoV-2 spike, the receptor binding domain of spike, and nucleocapsid were assessed. Multivariable regression was used to assess risk factors for infection. RESULTS: Of 2834 participants, 85% were female, 81% were teaching staff, and 86% had received at least one dose of SARS-CoV-2 vaccine. Of the 1983 who had been tested via a respiratory specimen, 4.9% reported a positive test. Five additional participants had serologic testing suggestive of a previous infection (3.6% overall incidence). In multivariable regression analysis, risk factors for infection included exposure to a SARS-CoV-2 infected adult (adjusted incidence rate ratio (aIRR) 13.6; 95% confidence interval 8.6, 21.3) or child (aIRR 2.3; 1.3, 4.2) in the household, or school student (aIRR 1.9; 1.2, 3.2), or travel outside the province within 14 days of testing (aIRR 6.0; 1.5, 23.6). CONCLUSION: In the first 18 months of the pandemic, education workers had a similar risk of infection with SARS-CoV-2 as other Ontario residents. Practicing protective measures whenever any household member has been exposed to a possible case and at all times when exposed to anyone from outside the home would help reduce the risk of infection.

RéSUMé: OBJECTIF: Estimer l'incidence du SRAS-CoV-2 chez les travailleuses et les travailleurs en éducation et les facteurs associés à l'infection entre mars 2020 et juillet 2021. MéTHODE: Étude prospective de cohortes auprès de travailleuses et de travailleurs en éducation travaillant ≥8 heures par semaine en Ontario, au Canada. Les participants ont autodéclaré les résultats de tests de dépistage du SRAS-CoV-2 et répondu à des questionnaires en ligne portant sur leurs données démographiques, leurs expositions au SRAS-CoV-2 et leurs vaccins contre le virus. Les participants ont soumis des gouttes de sang séché autoprélevées. Les anticorps à la protéine S du SRAS-CoV-2, le domaine de liaison aux récepteurs de la protéine S et la nucléocapside ont été évalués. Une régression multivariée a servi à évaluer les facteurs de risque d'infection. RéSULTATS: Sur les 2 834 participants, 85 % étaient des femmes, 81 % étaient des enseignants et 86 % avaient reçu au moins une dose de vaccin contre le SRAS-CoV-2. Sur les 1 983 personnes ayant été testées au moyen d'un prélèvement respiratoire, 4,9 % ont déclaré un test positif. Chez cinq autres participants, un test sérologique a indiqué une infection antérieure (incidence globale de 3,6 %). Selon l'analyse de régression multivariée, les facteurs de risque d'infection étaient l'exposition à un adulte infecté par le SRAS-CoV-2 (rapport de taux d'incidence ajusté [RTIa] 13,6; intervalle de confiance de 95 % 8,6, 21,3) ou à un enfant infecté (RTIa 2,3; 1,3, 4,2) au sein du ménage, l'exposition à un élève infecté (RTIa 1,9; 1,2, 3,2) ou un déplacement hors province dans les 14 jours ayant précédé le test (RTIa 6,0; 1,5, 23,6). CONCLUSION: Au cours des 18 premiers mois de la pandémie, le risque d'infection par le SRAS-CoV-2 chez les travailleuses et les travailleurs en éducation était semblable au risque des autres résidents de l'Ontario. L'application de mesures de protection chaque fois qu'un membre du ménage a été exposé à un cas possible, et en tout temps lorsqu'on est exposé à une personne de l'extérieur du ménage, contribuerait à réduire le risque d'infection.

Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for the prevention and treatment of SARS-CoV-2 infections. We evaluated the antiviral activity of sulforaphane (SFN), the principal biologically active phytochemical derived from glucoraphanin, the naturally occurring precursor present in high concentrations in cruciferous vegetables. SFN inhibited in vitro replication of six strains of SARS-CoV-2, including Delta and Omicron, as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN should be explored as a potential agent for the prevention or treatment of coronavirus infections.

A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination.

Objectives: Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. Methods: We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. Results: Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. Conclusions: Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter-laboratory data comparison and aggregation.

Dried blood spot specimens for SARS-CoV-2 antibody testing: A multi-site, multi-assay comparison.

The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.

Cross-validation of ELISA and a portable surface plasmon resonance instrument for IgG antibody serology with SARS-CoV-2 positive individuals.

We report on the development of surface plasmon resonance (SPR) sensors and matching ELISAs for the detection of nucleocapsid and spike antibodies specific against the novel coronavirus 2019 (SARS-CoV-2) in human serum, plasma and dried blood spots (DBS). When exposed to SARS-CoV-2 or a vaccine against SARS-CoV-2, the immune system responds by expressing antibodies at levels that can be detected and monitored to identify the fraction of the population potentially immunized against SARS-CoV-2 and support efforts to deploy a vaccine strategically. A SPR sensor coated with a peptide monolayer and functionalized with various sources of SARS-CoV-2 recombinant proteins expressed in different cell lines detected human anti-SARS-CoV-2 IgG antibodies in clinical samples. Nucleocapsid expressed in different cell lines did not significantly change the sensitivity of the assays, whereas the use of a CHO cell line to express spike ectodomain led to excellent performance. This bioassay was performed on a portable SPR instrument capable of measuring 4 biological samples within 30 minutes of sample/sensor contact and the chip could be regenerated at least 9 times. Multi-site validation was then performed with in-house and commercial ELISA, which revealed excellent cross-correlations with Pearson's coefficients exceeding 0.85 in all cases, for measurements in DBS and plasma. This strategy paves the way to point-of-care and rapid testing for antibodies in the context of viral infection and vaccine efficacy monitoring.

Multisystem Inflammatory Syndrome Associated with COVID-19 Anti-thrombosis Guideline of Care for Children by Action.

With growing number of pediatric cases of COVID-19, a unique hyper-inflammatory syndrome, linked to SARS-CoV-2 infection, has emerged in children referred to as multisystem inflammatory syndrome in children (MIS-C). This Kawasaki Disease (KD)-like illness has been described across the world. This syndrome shares features of KD, toxic shock syndrome, and macrophage activation syndrome and is associated with significantly elevated inflammatory markers. Everyday there are new data emerging improving the care of these patients. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative network designed to improve the outcomes of pediatric patients with end-stage heart failure and involves centers from across North America. The committee gathered information concerning COVID-19 anticoagulation practices at various centers and harmonized the data to formulate a set of recommendations.

ST-Elevation Myocardial Infarction due to Acute Thrombosis in an Adolescent With COVID-19.

STEMI can be the presenting diagnosis in adults with COVID-19; presented is a case of a 15-year-old girl with coronary thrombosis-induced STEMI associated with COVID-19. ST-elevation myocardial infarction (MI) is an identified presentation of coronavirus disease 2019 in adults but has not been reported in children. We present a case of a 15-year-old girl with a coronary thrombosis-induced ST-elevation MI in the setting of acute severe acute respiratory syndrome coronavirus 2 infection, not associated with multisystem inflammatory syndrome in children. The patient presented with chest pain, ST elevation, and myocardial dysfunction. Coronary angiography identified thrombosis treated with anticoagulation and antiplatelet therapy. MI must be considered in children who present with coronavirus disease 2019-associated myocardial dysfunction.

Prevalence and Persistent Shedding of Fecal SARS-CoV-2 RNA in Patients With COVID-19 Infection: A Systematic Review and Meta-analysis.

INTRODUCTION: The prevalence and shedding of fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA indicate coronavirus disease 2019 (COVID-19) infection in the gastrointestinal (GI) tract and likely infectivity. We performed a systemic review and meta-analysis to evaluate the prevalence and the duration of shedding of fecal RNA in patients with COVID-19 infection. METHODS: PubMed, Embase, Web of Science, and Chinese databases Chinese National Knowledge Infrastructure and Wanfang Data up to June 2020 were searched for studies evaluating fecal SARS-CoV-2 RNA, including anal and rectal samples, in patients with confirmed COVID-19 infection. The pooled prevalence of fecal RNA in patients with detectable respiratory RNA was estimated. The days of shedding and days to loss of fecal and respiratory RNA from presentation were compared. RESULTS: Thirty-five studies (N = 1,636) met criteria. The pooled prevalence of fecal RNA in COVID-19 patients was 43% (95% confidence interval [CI] 34%-52%). Higher proportion of patients with GI symptoms (52.4% vs 25.9%, odds ratio = 2.4, 95% CI 1.2-4.7) compared with no GI symptoms, specifically diarrhea (51.6% vs 24.0%, odds ratio = 3.0, 95% CI 1.9-4.8), had detectable fecal RNA. After loss of respiratory RNA, 27% (95% CI 15%-44%) of the patients had persistent shedding of fecal RNA. Days of RNA shedding in the feces were longer than respiratory samples (21.8 vs 14.7 days, mean difference = 7.1 days, 95% CI 1.2-13.0). Furthermore, days to loss of fecal RNA lagged respiratory RNA by a mean of 4.8 days (95% CI 2.2-7.5). DISCUSSION: Fecal SARS-CoV-2 RNA is commonly detected in COVID-19 patients with a 3-fold increased risk with diarrhea. Shedding of fecal RNA lasted more than 3 weeks after presentation and a week after last detectable respiratory RNA.