Adequacy of serial self-performed SARS-CoV-2 rapid antigen-detection testing for longitudinal mass screening in the workplace (preprint)

Importance: Longitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on implementation of accurate self-performed RADT testing where people live, work, or attend school. Objective: To quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results. We compared results using the instructions provided by the manufacturer to those with modified instructions that were informed by the most frequent or most critical errors we observed. Design: Repeated cross-sectional, diagnostic accuracy study performed prospectively in the field. Setting: Businesses in Montreal, Quebec, Canada, with at least 2 active cases of SARS-CoV-2 infection. Participants: Untrained, asymptomatic persons in their workplace, not meeting Public Health quarantine criteria. Exposures: A Modified Quick Reference Guide compared to the original manufacturer's instructions. Main Outcome(s) and Measure(s): The difference in the proportions of correctly performed procedural steps, and the difference in proportions of correctly interpreted RADT proficiency panel results. The secondary outcome, among subjects with two self-testing visits, compared the second to the first self-test visit using the same measures. Results: Overall, 1892 tests were performed among 647 subjects. For self-test visit 1, significantly better accuracy in test interpretation was observed using the Modified Quick Reference Guide for weak positive (55.6% vs. 12.3%; 43.3 percentage point improvement, 95% confidence interval [CI] 33.0%-53.8%), positive (89.6% vs. 51.5%; 38.1% difference, 95%CI 28.5%-47.5%), strong positive (95.6% vs. 84.0%; 11.6% improvement, 95%CI 6.8%-16.3%) and invalid (87.3% vs. 77.3%; 10.0% improvement, 95%CI 3.8%-16.3%) tests. Use of the modified guide was associated with smaller, statistically significant, improvements on self-test visit 2. For procedural steps identified as critical for the validity of test results, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. Conclusions and Relevance: Longitudinal mass RADT testing for SARS-CoV-2 can be accurately self-performed in an intended-use setting; this work provides evidence for how to optimise performance.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study (preprint)

Importance: Children are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established. Objective: To identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection. Design: Cohort study, enrollment from February 1, 2020 until May 31, 2021 Setting 15 children's hospitals in Canada, Iran, and Costa Rica Participants: Patients <18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C) Exposures: Variables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings. Main Outcomes and Measures: The primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of [≥]6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease. Results: We identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p<0.001), were more frequently present in adolescents [≥]12 years of age. Neurological disorder (3.16, 1.19-8.43) in children <12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors. Conclusions and Relevance: Pediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.

Specificity of SARS-CoV-2 antibody-detection assays against S and N protein among pre-COVID-19 sera from patients with protozoan and helminth parasitic infections (preprint)

BackgroundWe aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections. MethodsWe tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera. ResultsThe specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all [≥] 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay. ConclusionsThe specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.

Multicenter cohort study of children hospitalized with SARS-CoV-2 infection (preprint)

Background: A cohort study was conducted to describe and compare the burden and characteristics of SARS-CoV-2 infection in hospitalized children in three countries. Methods: This was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology. Results: Of 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; p<0.001) and less likely to require mechanical ventilation (3/95 [3%] versus 15/116 [13%]; p<0.05). Requirement for oxygen or ICU occurred in 64 (30%) and death in four, three of whom. had malignancies. Age < 30 days, admission outside of Canada, presence of at least one comorbidity and chest imaging compatible with COVID-19 predicted severe disease. Conclusions: Approximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease was more severe at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe disease.

Evaluation of a Commercial Culture-free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison with an Anti-RBD ELISA Assay (preprint)

BackgroundSARS-CoV-2 surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript) is the first such commercially available assay, detecting antibodies that block RBD/ACE-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared to anti-RBD ELISA assays. MethodsSerum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD IgG, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection. ResultsCompared to PRNT-50, cPass sensitivity ranged from 77% - 100% and specificity was 95% - 100%. Sensitivity was also high compared to the pseudotyped lentiviral neutralization assay (93% [95%CI 85-97]), but specificity was lower (58% [95%CI 48-67]). Highest agreement between cPass and ELISA was for anti-RBD IgG (r=0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99% [95%CI 94-100]) was very similar to that of cPass, but overall specificity was lower (37% [95%CI 28-47]). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical. ConclusionsThe added value of cPass compared to an IgG anti-RBD ELISA was modest.