Student-led curricular approaches in medical education: the educational effects of a virtual fundamentals of COVID-19 course.

BACKGROUND: As the field of education was adapting to virtual learning during the COVID-19 pandemic, a need quickly emerged for a course to prepare medical students for future clinical practice. This call to action was answered by creating an innovative Fundamentals of COVID-19 course at the Indiana University School of Medicine (IUSM). As a group of medical student leaders at IUSM, we developed this online course in order to support our fellow students and the community. METHODS: The study examined the educational effects of completing the Fundamentals of COVID-19 course. In order to examine these effects, the study asked enrolled students to complete both a pre- and post-course self-assessment survey. Students were asked an identical set of questions on each survey about their knowledge, skills, and abilities (KSA) regarding COVID-19. Composite scores were created for each KSA learning domain. Responses were provided using a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. RESULTS: Out of the 724 students enrolled, 645 students completed both the pre- and post-course assessment surveys. Findings show that there were both meaningful and statistically significant differences in students' responses to the pre- and post-course surveys. Results show 1.) a significant mean increase in the knowledge composite score of 1.01, 95% CI [0.95, 1.06], t(644) = 36.4, p < .001, d = 1.43; 2.) a significant mean increase in the skills composite score of .55, 95% CI [0.50, 0.60], t(644) = 20.70, p < .001, d = 0.81. and 3.) a significant mean increase of the abilities composite score of 1.02, 95% CI [.97, 1.07], t(644) = 36.56, p < .001, d = 1.44. CONCLUSIONS: These findings demonstrate that the student-developed, online Fundamentals of COVID-19 course resulted in notable and statistically significant educational effects. The increase in students' self-reported ratings, especially in the knowledge and abilities domains, indicate that meaningful learning occurred within the course. These findings have notable implications for medical student training during healthcare emergencies, such as a pandemic, as well as within modern clerkship environments. Overall, our findings provide evidence that student-led curricular design and virtual delivery of course content can be effective tools in undergraduate medical education.

Performance of six SARS-CoV-2 RNA detection systems in symptomatic and asymptomatic pediatric and maternal patients.

Aim: This study evaluated the real-world performance of six test systems for detection of SARS-CoV-2 in 138 pediatric and 110 adult maternal patients. Materials & methods: Nasopharyngeal swabs were tested directly using the Aptima™ SARS-CoV-2 (Aptima) and Simplexa™ COVID-19 Direct (Simplexa), and with Altona RealStar® RT-PCR and CDC RT-PCR with nucleic acid extracted on the Roche® MagNA Pure 96 (Altona-MP96) or bioMérieux EMAG® (Altona-EMAG). Results/Conclusion: Overall percent-positive and percent-negative agreements among the six test systems were, respectively: Aptima: 94.8 and 100%; Altona-MP96: 96.5 and 99.3%; CDC-MP96: 100 and 99.3%; Altona-EMAG: 86.1 and 100%; CDC-EMAG: 98.2 and 100%; Simplexa: 87 and 99.2%. The six test systems showed agreement ranging from 92.7 (κ = 0.85) to 98.8% (κ = 0.98).

Comparison of Mid-Turbinate and Nasopharyngeal Specimens for Molecular Detection of SARS-CoV-2 Among Symptomatic Outpatients at a Pediatric Drive-Through Testing Site.

BACKGROUND: Nasopharyngeal (NP) specimen testing by reverse transcriptase polymerase chain reaction (RT-PCR) is the standard of care for detecting SARS-CoV-2. Data comparing the sensitivity and specificity of the NP specimen to the less invasive, mid-turbinate (MT) nasal specimen in children are limited. METHODS: Paired clinical NP and research MT specimens were collected from children <18 years with respiratory symptoms and tested by molecular assays to detect SARS-CoV-2 RNA. Sensitivity, specificity, and agreement (Cohen's kappa [κ]) were calculated for research MT specimens compared to the clinical NP specimens. RESULTS: Out of 907 children, 569 (62.7%) had parental consent and child assent when appropriate to participate and provided paired MT and NP specimens a median of 4 days after symptom onset (range 1-14 days). 16.5% (n = 94) of MT specimens were positive for SARS-CoV-2 compared with 20.0% (n = 114) of NP specimens. The sensitivity of research MT compared to clinical NP specimens was 82.5% (95% CI: 74.2%, 88.9%), specificity was 100.0% (95% CI: 99.2%, 100.0%), and overall agreement was 96.1% (κ = 0.87). The sensitivity of MT specimens decreased with time from 100% (95% CI: 59.0%, 100.0%) on day 1 of illness to 82.1% (95% CI: 73.8%, 88.7%) within 14 days of illness onset; sensitivity was generally >90% when specimens were collected within the first week of illness. CONCLUSION: MT specimens, particularly those collected within the first week of illness, have moderately reduced sensitivity and equivalent specificity to less-tolerated NP specimens in pediatric outpatients. MT specimen use in children may represent a viable alternative to NP specimen collection.

Recombinant rod domain of vimentin binds to spike protein to block SARS-CoV-2 replication in vitro

The COVID-19 pandemic, caused by SARS-CoV-2, has infected at least 85 million people worldwide and led to over 1.8 million deaths. To date, there are no approved efficacious treatments targeting SARS-CoV-2, with current tactics (e.g. modulating the host response R2 0.9858;Fig. 1 A-B). Heat inactivation (100°C for 10 minutes) of rhRod (?rhRod) did not bind to spike protein (indeterminate;R2 0;Fig. 1 C-D). We then tested whether rhRod blocked ACE2 from binding to spike protein using 2 methods (Fig. 1 E-F). Immobilized spike protein sensors were first placed in rhRod (0-1000 nM) containing wells then placed into wells with 200 nM ACE2. The IC50 of rhRod was 139 ± 17 nM (R2 0.9959). A separate series of experiments were done using immobilized ACE2 sensors placed in wells containing 125 nM spike protein mixed with increasing concentrations of rhRod (0-500 nM). As the concentration of rhRod increased, binding to ACE2 sensors decreased, with an IC50 of 34 ± 8 nM (R2 0.9845). Based on our findings, we used in silico modeling (SwarmDock) to asses the predicted interactions between rhRod and spike. We found that rhRod was predicted to bind to spike protein in the same region as ACE2, consistent with our empirical data that rhRod blocks spike-ACE2 interactions. Finally, to test whether rhRod decreased SARS-CoV-2 replication, we infected Vero E6 cells with SARS-CoV-2 (USA-WA1/2020;MOI 0.1) in the presence of rhRod (0-4,000 nM). Daily administration of rhRod decreased viral replication (PFU/mL) by 100-1000-fold (1000-4000 nM) starting at 48 hours, through 96 hours (segmental linear regression with least squares fit;Fig. 1G). ?rhRod (4000 nM) had no effect on viral replication. Our data show that rhRod binds to spike protein to block spike-ACE2 interactions and decreases SARS-CoV-2 viral replication in vitro. Data from these studies will inform preclinical models of COVID-19 to further develop a potential novel therapy for this devastating disease.

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Clinical Validation and Performance Evaluation of the Automated Vitros Total Anti-SARS-CoV-2 Antibodies Assay for Screening of Serostatus in COVID-19.

OBJECTIVES: Evaluation of serostatus against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as an important tool in identification of exposure to coronavirus disease 2019 (COVID-19). We report on the validation of the Vitros Anti-SARS-CoV-2 Total (CoV2T) assay for qualitative serologic testing of SARS-CoV-2 antibodies. METHODS: We performed validation studies according to Commission of Office Laboratories Accreditation guidelines, using samples previously tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR). We evaluated precision, analytical interferences, and cross-reactivity with other viral infections; evaluated concordance with molecular and other serologic testing; and evaluated seroconversion. RESULTS: The Vitros CoV2T assay exhibited acceptable precision and did not exhibit cross-reactivity with other acute respiratory virus infections. The CoV2T assay exhibited 100% negative predictive agreement (56/56) and 71% positive predictive agreement (56/79) with RT-PCR across all patient samples and was concordant with other serologic assays. Concordance with RT-PCR was 97% more than 7 days after symptom onset. The CoV2T assay was robust to icterus and lipemia but had interference from significant hemolysis. CONCLUSIONS: The Vitros CoV2T assay was successfully validated in our laboratory. We anticipate it will be a useful tool in screening for exposure to SARS-CoV-2; however, the use of the CoV2T and other serologic assays in the clinical management of patients with COVID-19 is unknown and must be evaluated in future studies.