Accurate diagnosis of acute severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection is critical for appropriate management of patients with this disease. We examined the possible complementary role of lab developed class-specific clinical serology in assessing SARS-CoV-2 infection in hospitalized patients. Serological tests for IgG, IgA, and IgM antibodies against the receptor binding domain (RBD) of SARS-CoV-2 were evaluated using samples from real time RT PCR (qRT-PCR)-confirmed in-patient COVID-19 cases. We analyzed the influence of timing and clinical severity on the diagnostic value of class-specific coronavirus disease 2019 (COVID-19) serology testing. Cross-sectional analysis revealed a higher sensitivity and specificity at lower optical density cutoffs for IgA in hospitalized patients when compared to IgG and IgM serology (IgG area under the curve (AUC): 0.91; 95%CI 0.89 to 0.93 vs. IgA AUC: 0.97; 95% CI 0.96 to 0.98 vs. IgM AUC: 0.95; 95% CI 0.92 to 0.97). The enhanced performance of IgA serology was apparent in the first two weeks after symptom onset and the first week after PCR testing. In patients requiring intubation, all three tests exhibit enhanced sensitivity. Among PCR-negative patients under investigation for SARS-CoV-2 infection 2 out of 61 showed clear evidence of seroconversion IgG, IgA and IgM. Suspected false-positive results in the latter population were most frequently observed in IgG and IgM serology tests. Our findings suggest the potential utility of IgA serology in the acute setting and explore the benefits and limitations of class-specific serology as a complementary diagnostic tool to PCR for COVID-19 in the acute setting.
Introduction On March 17, 2020 the AAMC recommended dismissal of medical students from clinical settings due to the COVID-19 pandemic. Third-year (M3) and fourth-year (M4) medical students were at home, M4s were interested in teaching, and residents and faculty had fewer clinical responsibilities due to elective surgery cancellations. To continue M3 access to education, we created a virtual surgery elective (VSE) that aimed to broaden students’ exposure to, and elicit interest in, general surgery (GS). Methods Faculty, surgical residents, and M4s collaborated to create a two-week VSE focusing on self-directed learning and direct interactions with surgery faculty. Each day was dedicated to a specific pathology commonly encountered in GS. A variety of teaching methods were employed including self-directed readings and videos, M4 peer lectures, case-based learning and operative video review with surgery faculty, and weekly surgical conferences. A VSE skills lab was also conducted to teach basic suturing and knot-tying. All lectures and skills labs were via Zoom videoconference (Zoom Video Communications Inc). A post-course anonymous survey sent to all participants assessed changes in their understanding of GS and their interest in GS and surgery overall. Results Fourteen M3s participated in this elective over two consecutive iterations. The survey response rate was 79%. Ninety-one percent of students believed the course met its learning objectives “well” or “very well.” Prior to the course, 27% reported a “good understanding” and 0% a “very good” understanding of GS. Post-course, 100% reported a “good” or “very good” understanding of GS, a statistically significant increase (p=0.0003). Eighty-two percent reported increased interest in GS and 64% reported an increase in pursuing GS as a career (Table 1). Conclusion As proof of concept, this online course successfully demonstrated virtual medical student education can increase student understanding of GS topics, increase interest in GS, and increase interest in careers in surgery. To broaden student exposure to GS, we plan to integrate archived portions of this course into the regular third-year surgery clerkship and these can also be used to introduce GS in the preclinical years.
Redirection of T cell cytotoxicity by the chimeric antigen receptor (CAR) structure may not be sufficient for optimal antitumor function in the patient tumor microenvironment. Comodifying CAR T cells to secrete different classes of proteins can be used to optimize CAR T cell function, overcome suppressive signals, and/or alter the tumor microenvironment milieu. These modifications aim to improve initial responses to therapy and enhance the durability of response. Furthermore, CAR T cells can deliver these molecules locally to the tumor microenvironment, avoiding systemic distribution. This approach has been tested in preclinical models using a variety of different classes of agonistic and antagonistic proteins, and clinical trials are currently underway to assess efficacy in patients.
310 Figure 1 (A) Unmodified Panc1 cells do not express Muc16CD but do express VIP. PDX PDAC cells express Muc16CD and VIP by flow cytometry. (B) Anti-Muc16CD CAR T cells are capable of cytotoxic function against PDX PDAC cells in vitro.
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