T-cell responses in COVID-19 survivors 6-8 months after infection: A longitudinal cohort study in Pune.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response is crucial for disease management, although diminishing immunity raises the possibility of reinfection. METHODS: We examined the immunological response to SARS-CoV-2 in a cohort of convalescent COVID-19 patients in matched samples collected at 1 and 6-8 months after infection. The peripheral blood mononuclear cells were isolated from enrolled study participants and flow cytometry analysis was done to assess the lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells in COVID-19 patients at 1 and 6-8 months after infection. Immunophenotypic characterization of immune cell subsets was performed on individuals who were followed longitudinally for 1 month (n = 44) and 6-8 months (n = 25) after recovery from COVID infection. RESULTS: We observed that CD4 +T cells in hospitalized SARS-CoV-2 patients tended to decrease, whereas CD8+ T cells steadily recovered after 1 month, while there was a sustained increase in the population of effector T cells and effector memory T cells. Furthermore, COVID-19 patients showed persistently low B cells and a small increase in the NK cell population. CONCLUSION: Our findings show that T cell responses were maintained at 6-8 months after infection. This opens new pathways for further research into the long-term effects in COVID-19 immunopathogenesis.

Lymphopenia with Altered T Cell Subsets in Hospitalized COVID-19 Patients in Pune, India.

The cellular immune cell subsets affecting COVID-19 disease severity are being studied by researchers from many countries. The current study was carried out to investigate the alteration of peripheral blood mononuclear cells (PBMCs) and their subsets in hospitalized COVID-19 patients in a tertiary care center in Pune, India. The PBMCs were isolated from enrolled study participants, and flow cytometry analysis was done to assess peripheral white blood cell alterations. The lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells were then evaluated in COVID-19 patients with different disease categories and compared to healthy controls. The immunophenotypic characterization of the immune cell subset was done for 139 COVID-19 patients and 21 healthy controls. These data were evaluated based on the disease severity. A total of 139 COVID-19 patients were classified as mild (n = 30), moderate (n = 57), or severe (n = 52) cases. The decreased percentages of total lymphocytes, CD3+ T cells, CD4+ T cells, naive T cells, central memory T cells, and Natural Killer (NK) cytotoxic cells were found, and there was increase in effector T (TEf) cells and effector memory T cells in patients with severe COVID-19 compared to healthy controls. The severity of SARS-CoV-2 infection has an effect on lymphocyte subsets, resulting in reduced T memory cells and NK cells but increased TEf cells in severe cases. Clinical Trial Registration: CTRI ID-CTRI/2021/03/032028.

Tuberculosis (TB) Aftermath: study protocol for a hybrid type I effectiveness-implementation non-inferiority randomized trial in India comparing two active case finding (ACF) strategies among individuals treated for TB and their household contacts.

BACKGROUND: Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). METHODS: We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month "mop-up" visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB. DISCUSSION: This novel trial will guide India's scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings. TRIAL REGISTRATION: NCT04333485 , registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.