Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children

Objective To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. Design Multicentre retrospective cohort study. Setting 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. Patients Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). Main outcome measure Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. Results We identified 403 hospitalisations. 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). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45–9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. Conclusion We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Adequacy of Serial Self-performed SARS-CoV-2 Rapid Antigen Detection Testing for Longitudinal Mass Screening in the Workplace.

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 accurate self-testing. 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. Design, Setting, and Participants: This prospective repeated cross-sectional study was performed from July to October 2021 at businesses with at least 2 active cases of SARS-CoV-2 infection in Montreal, Canada. Participants included untrained persons in their workplace, not meeting Public Health quarantine criteria (ie, required quarantine for 10 days after a moderate-risk contact with someone infected with SARS-CoV-2). Interpretation and performance were compared between participants who received instructions provided by the manufacturer vs those who received modified instructions that were informed by the most frequent or most critical errors we observed. Data were analyzed from October to November 2021. Exposures: RADT testing using a modified quick reference guide compared with the original manufacturer's instructions. Main Outcomes and Measures: The main outcome was the difference in correctly interpreted RADT results. Secondary outcomes included difference in proportions of correctly performed procedural steps. Additional analyses, assessed among participants with 2 self-testing visits, compared the second self-test visit with the first self-test visit using the same measures. Results: Overall, 1892 tests were performed among 647 participants, of whom 278 participants (median [IQR] age, 43 [31-55] years; 156 [56.1%] men) had at least 1 self-testing visit. For self-test visit 1, significantly better accuracy in test interpretation was observed among participants using the modified quick reference guide than those using the manufacturer's instructions for reading results that were weak positive (64 of 115 participants [55.6%] vs 20 of 163 participants [12.3%]; difference, 43.3 [95% CI, 33.0-53.8] percentage points), positive (103 of 115 participants [89.6%] vs 84 of 163 participants [51.5%]; difference, 38.1 [95% CI, 28.5-47.5] percentage points), strong positive (219 of 229 participants [95.6%] vs 274 of 326 participants [84.0%]; difference, 11.6 [95% CI, 6.8-16.3] percentage points), and invalid (200 of 229 participants [87.3%] vs 252 of 326 participants [77.3%]; difference, 10.0 [95% CI, 3.8-16.3] percentage points). Use of the modified guide was associated with improvements on self-test visit 2 for results that were weak positive (difference, 15.4 [95% CI, 0.7-30.1] percentage points), positive (difference, 19.0 [95% CI, 7.2-30.9] percentage points), and invalid (difference, 8.0 [95% CI, 0.8-15.4] percentage points). For procedural steps identified as critical for test validity, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. Conclusions and Relevance: In this cross-sectional study of self-performed SARS-CoV-2 RADT in an intended-use setting, a modified quick reference guide was associated with significantly improved accuracy in RADT interpretations.

Specificity of SARS-CoV-2 Antibody Detection Assays against S and N Proteins among Pre-COVID-19 Sera from Patients with Protozoan and Helminth Parasitic Infections.

We aimed to assess the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection assays among people with tissue-borne parasitic infections. We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 neutralization antibody detection kit [cPass], Abbott SARS-CoV-2 IgG assay [Abbott Architect], and Standard Q COVID-19 IgM/IgG combo rapid diagnostic test [SD RDT IgM/SD RDT IgG]) among 559 pre-COVID-19 seropositive sera for several parasitic infections. The specificity of assays was 95 to 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 to 95]) and visceral leishmaniasis (SD RDT IgG; 80% [95% CI, 30 to 99]), and from patients with recent malaria in areas of Senegal where malaria is holoendemic (ranging from 91% for Abbott Architect and SD RDT IgM to 98 to 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 to 100%. The majority (>85%) of false-positive results were positive by only one assay. The 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.

SARS-CoV-2 Clinical Characteristics and Viral Shedding in Kuwait.

OBJECTIVES: We aimed to describe the clinical characteristics of SARS-CoV-2 infection and estimate viral shedding duration in respiratory specimens. METHODS: A retrospective cohort study was performed from February 25 to March 25, 2020. In Kuwait, all suspected coronavirus disease 2019 (COVID-19) cases, contacts of cases, and returning travelers were systematically tested for SARS-CoV-2 by RT-PCR. All infected persons, regardless of symptoms, were hospitalized and serially tested until they had two negative results. Descriptive statistics and regression analyses were performed. RESULTS: Two hundred seven cases of SARS-CoV-2 infection were included in this study. About half of the cases were asymptomatic and 1.9% died. The median time to negative RT-PCR was 22 days. Increasing age, ARDS, and low peripheral white blood cell count were associated with prolonged PCR positivity. CONCLUSION: Predictors for prolonged RT-PCR positivity included increasing age, ARDS, and low white blood cell count. The findings of this study may aid in better understanding of the epidemiology of SARS-CoV-2 infection and molecular testing dynamics.

Evaluation of a Commercial Culture-Free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison With an Antireceptor-Binding Domain Enzyme-Linked Immunosorbent Assay.

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-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 that detects antibodies that block receptor-binding domain (RBD)/angiotensin-converting enzyme (ACE)-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared with anti-RBD enzyme-linked immunosorbent assays (ELISAs). METHODS: Serum 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 immunoglobulin (Ig)G, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection. RESULTS: Compared with PRNT-50, cPass sensitivity ranged from 77% to 100% and specificity was 95% to 100%. Sensitivity was also high compared with the pseudotyped lentiviral neutralization assay (93%; 95% confidence interval [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. CONCLUSIONS: The added value of cPass compared with an IgG anti-RBD ELISA was modest.

Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus 2 : A Narrative Review.

Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.