Enhanced SARS-CoV-2-Specific CD4+ T Cell Activation and Multifunctionality in Late Convalescent COVID-19 Individuals

Background: Examination of CD4(+) T cell responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection offers useful information for the improvement of vaccination strategies against this virus and the protective effect of these T cells. Methods: We characterized the SARS-CoV-2-specific CD4(+) T cell activation marker, multifunctional cytokine and cytotoxic marker expression in recovered coronavirus disease 2019 (COVID-19) individuals. Results: CD4(+) T-cell responses in late convalescent (>6 months of diagnosis) individuals are characterized by elevated frequencies of activated as well as mono, dual- and multi-functional Th1 and Th17 CD4(+) T cells in comparison to early convalescent (<1 month of diagnosis) individuals following stimulation with SARS-CoV-2-specific antigens. Similarly, the frequencies of cytotoxic marker expressing CD4(+) T cells were also enhanced in late convalescent compared to early convalescent individuals. Conclusion: Our findings from a low-to middle-income country suggest protective adaptive immune responses following natural infection of SARS-CoV-2 are elevated even at six months following initial symptoms, indicating the CD4(+) T cell mediated immune protection lasts for six months or more in natural infection

Characterization of memory T cell subsets and common γ−chain cytokines in convalescent COVID-19 individuals

T cells are thought to be an important correlates of protection against SARS‐CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS‐CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ−chain in 7 groups of COVID‐19 individuals, based on days since RT‐PCR confirmation of SARS‐CoV‐2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4(+) central and effector memory cells increased, and the frequencies of CD4(+) naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15–30 to Days 61–90 and plateaued thereafter. In addition, the frequencies of CD8(+) central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8(+) naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15–30 to Days 61–90 and plateaued thereafter. The plasma levels of IL‐2, IL‐7, IL‐15, and IL‐21—common γc cytokines started decreasing from Days 15–30 till Days 151–180. Severe COVID‐19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL‐2, IL‐7, IL‐15, and IL‐21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ−chain cytokines in convalescent COVID‐19 individuals

Hospitalization Rates and Direct Medical Costs for Fever in a Pediatric Cohort in South India

Primary data on causes and costs of hospitalization are necessary for costing and cost-effectiveness analysis. Data on incidence and causes of hospitalization and consequent expenses among Indian children are limited. A cohort of 6000 children aged 0.5-15 years residing in urban Vellore was followed for 3 years, under the Vellore Typhoid Study, 2016-2017, and later under the Surveillance for Enteric Fever project, 2017-2019. Data on hospitalization events and associated antibiotic use, and direct medical costs for fever-related hospitalization of study children were obtained from caregivers through weekly follow-up by study field workers. The incidence of hospitalization was 33 per 1000 child-years of observation. Children aged 0.5-5 years had the highest incidence of hospitalization. The top 5 infectious causes for hospitalization were acute undifferentiated fevers, respiratory tract infections, acute gastroenteritis, enteric fever, and dengue. The overall median cost of hospitalization for fever was 4243 (interquartile range, 2502-7215) Indian rupees (INR). An episode of dengue had a median cost of 5627 INR, followed by acute undifferentiated fevers and enteric fever with median costs of 3860 and 3507 INR, respectively. Hospitalization for fever is common in young children and impacts household finances in low-income Indian households

Trimetallic Oxide Electrocatalyst for Enhanced Redox Activity in Zinc–Air Batteries Evaluated by In Situ Analysis

Abstract Researchers are investigating innovative composite materials for renewable energy and energy storage systems. The major goals of this studies are i) to develop a low‐cost and stable trimetallic oxide catalyst and ii) to change the electrical environment of the active sites through site‐selective Mo substitution. The effect of Mo on NiCoMoO4 is elucidated using both in situ X‐ray absorption spectroscopy and X‐ray diffraction analysis. Also, density functional theory strategies show that NiCoMoO4 has extraordinary catalytic redox activity because of the high adsorption energy of the Mo atom on the active crystal plane. Further, it is demonstrated that hierarchical nanoflower structures of NiCoMoO4 on reduced graphene oxide can be employed as a powerful bifunctional electrocatalyst for oxygen reduction/evolution reactions in alkaline solutions, providing a small overpotential difference of 0.75 V. Also, Zn–air batteries based on the developed bifunctional electrocatalyst exhibit outstanding cycling stability and a high‐power density of 125.1 mW cm−2. This work encourages the use of Zn–air batteries in practical applications and provides an interesting concept for designing a bifunctional electrocatalyst

Factors Predicting Blood Culture Positivity in Children With Enteric Fever

Blood culture, despite low sensitivity, is the gold standard for enteric fever diagnosis. Understanding predictors of blood culture positivity may help design strategies to optimize enteric fever diagnosis. A cohort of 6760 children aged 0.5-15 years was followed for 3 years for enteric fever with blood cultures in an automated system, for fevers >3 days. Factors affecting test positivity in fevers and participant-level predictors for culture refusals were analyzed using regression models. Overall, 6097 suspected typhoid/paratyphoid fever (STF) episodes were reported, of which 5703 (93.5%) STFs had sampling for blood cultures, with 394 (6.5%) refusals. Salmonella enterica serovar Typhi/Paratyphi positivity was culture-confirmed in 3.8% (218/5703) of STF episodes. Older children (odds ratio [OR], 1.96 [95% CI, 1.39-2.77]), larger blood volume inoculated (OR, 2.82 [95% CI, 1.71-4.66]), higher temperatures during fever (OR, 3.77 [95% CI, 2.89-4.91]), and fevers diagnosed as suspected typhoid or acute undifferentiated fever (OR, 6.06 [95% CI, 3.11-11.78]) had a higher probability of culture positivity. Antibiotics before culture did not decrease culture positivity. Blood culture refusals were higher for children from wealthier households or with milder illness. Performing blood cultures in older children with fever, especially those fevers with toxic presentation and increasing blood volume for inoculation are strategies to improve enteric fever detection in surveillance settings