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Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants. Here we use systems immunology, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences) from 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19 and 40 age- and sex-matched healthy controls with no history of COVID-19 to comparatively assess the post-infection immune status (mean: 151 days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination. Identification of both sex-specific and -independent temporally stable changes, including signatures of T-cell activation and repression of innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes, suggest that mild COVID-19 can establish new post-recovery immunological set-points. COVID-19-recovered males had higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males and COVID-19-recovered females, partly attributable to elevated pre-vaccination frequencies of a GPR56 expressing CD8+ T-cell subset in male recoverees that are "poised" to produce higher levels of IFN{gamma} upon inflammatory stimulation. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of the repressed genes in monocytes increased and moved towards the pre-vaccination baseline of healthy controls, suggesting that the acute inflammation induced by vaccination could partly reset the immune states established by mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19, and possibly respiratory viral infections in general, could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

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BACKGROUND: Team-based decision-making has been shown to reduce diagnostic error, increase clinical certainty, and decrease adverse events. OBJECTIVE: This study aimed to assess the effect of peer discussion on resident practice intensity (PI) and clinical certainty (CC). METHODS: A vignette-based instrument was adapted to measure PI, defined as the likelihood of ordering additional diagnostic tests, consultations or empiric treatment, and CC. Internal medicine residents at 7 programs in the Philadelphia area from April 2018 to June 2019 were eligible for inclusion in the study. Participants formed groups and completed each item of the instrument individually and as a group with time for peer discussion in between individual and group responses. Predicted group PI and CC scores were compared with measured group PI and CC scores, respectively, using paired t testing. RESULTS: Sixty-nine groups participated in the study (response rate 34%, average group size 2.88). The measured group PI score (2.29, SD = 0.23) was significantly lower than the predicted group PI score (2.33, SD = 0.22) with a mean difference of 0.04 (SD = 0.10; 95% CI 0.02-0.07; P = .0002). The measured group CC score (0.493, SD = 0.164) was significantly higher than the predicted group CC score (0.475, SD = 0.136) with a mean difference of 0.018 (SD = 0.073; 95% CI 0.0006-0.0356; P = .022). CONCLUSIONS: In this multicenter study of resident PI, peer discussion reduced PI and increased CC more than would be expected from averaging group members' individual scores.

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Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.

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Outbreaks of enteric fever are a major health concern not only due to significant human morbidity and mortality but also fear of spread of multidrug resistant strains. We report an outbreak of enteric fever caused by Salmonella enterica serotype Typhi in a suburban area, in city Chandigarh of North India. Twenty-seven strains of S. typhi were isolated from blood cultures over a period of two weeks with 18 of these 27 patients residing in the same area. Maximum cases were in the age group 5-14 years (10 patients, 55.5%) while 4 (22.2%) cases were children under 5 years. All the strains showed similar resistogram being resistant to ampicillin and nalidixic acid, intermediate to ciprofloxacin and sensitive to chloramphenicol, ceftriaxone, cefotaxime, cotrimoxazole and azithromycin on disc diffusion testing. Minimum inhibitory concentration of ciprofloxacin was determined by agar dilution method and was found to be raised (≥ 2 μ g/mL). This nalidixic acid resistant S. typhi outbreak report warrants the necessity of implementing stringent sanitation practices in public health interest.

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Objectives: The incidence of multidrug resistant enteric fever is increasing alarmingly. This study was planned to determine the rate of isolation of Salmonella spp. and to compare the isolates for their epidemiological parameters and antimicrobial susceptibility patterns at our center. Methods: The study was conducted over a span of three years with a total of 8142, 8134, and 8114 blood culture samples processed for the years 2008, 2009, and 2010 respectively. The minimum inhibitory concentration (MIC) for ciprofloxacin and chloramphenicol was determined using an agar dilution method. The MIC for ciprofloxacin was also confirmed by Epsilon-test (E -test) strips. Results: Of the total 302 Salmonella spp. isolated, 257 were Salmonella enterica serotype Typhi (85.1%) and 45 (14.9%) were S. enterica serotype Paratyphi A. The majority of the isolates recovered were from the pediatric age group (54.6%) and males (60.6%). Complete susceptibility was observed to chloramphenicol, cefotaxime, ceftriaxone, and azithromycin over the last two years (2009 and 2010), with an increase in resistance to nalidixic acid (100%) and ciprofloxacin (13.6%). Conclusions: In our study, we found augmentation of resistance to nalidixic acid and fluoroquinolones and complete sensitivity to ceftriaxone along with reemergence of chloramphenicol sensitivity for Salmonella isolates. This report emphasises the necessity of continuous surveillance of antibiograms of enteric fever isolates in an area.

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