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.

C-Reactive Protein Predicts COVID-19 Infection Severity and Length of Hospitalization

Chronic stress can lead to many systemic complications and low-grade systemic inflammation including increased levels of inflammatory cytokines, such as C-reactive protein (CRP). CRP is a marker of systemic inflammation and is associated with depression and perceived stress. Elevations can result in weakened immune responses, thereby increasing the risk of complications and mortality from infections. Recent evidence suggests that uncontrolled inflammatory responses associated with COVID-19 are a major determinant of disease severity. Purpose: The purpose of the study was to determine the effects of chronic stress, measured by CRP, on the severity and the length of hospitalization in COVID-19 patients. Methods: This retrospective study used medical records from patients admitted to the University Medical Center, El Paso, TX with COVID-19 (n=436 (272M/164F);age 57.3 ± 0.8 years;BMI 29.42 ± 0.3 Kg/m2). Chronic stress was measured by blood CRP level. Severity of COVID-19 infection was determined by the peripheral oxygen saturation (SpO2) measured during the time of hospitalization. Length of hospitalization was determined by the number of days spent in the hospital. Patients were categorized into low CRP (< 3mg/L) vs. high CRP (> 3mg/L) groups and were compared using unpaired t-test. Results: Patients with high CRP level had greater COVID-19 severity, measured by SpO2 (Low CRP: 94.2% ± 0.4 vs. high CRP: 91.9% ± 0.4;p<0.01), and greater length of hospital stay (low CRP: 6.5 ± 1.3 days vs. high CRP 8.8 ±0.5 days;p<0.05). CRP level was also negatively associated with SpO2 (r= -0.16, p<0.001) and positively associated with the length of hospitalization (r= 0.23, p<0.0001). Conclusion: Higher levels of CRP are associated with worsened severity and increased length of hospitalization in COVID-19 patients. CRP levels should be considered in laboratory workup for COVID-19 patients and treatment should focus on reducing inflammatory damage.

Unmanaged Diabetes as a Poor Prognostic Factor in the Severity of Infection and Recovery Time of Hospitalized COVID-19 Patients

Diabetes is considered as one of the comorbidities with COVID-19 infection and indicated to influence the severity and the rate of recovery in COVID-19 patients. However, it is not known whether the lack of diabetes management may magnify COVID-19 severity and the rate of recovery in patients with diabetes. Purpose: The purpose of this study was to determine the effect of diabetes management on the severity and length of hospitalization in hospitalized COVID-19 patients. Methods: This retrospective study used medical records from patients admitted to the University Medical Center, El Paso, TX with COVID-19 (n=369;Age 60.0 ± 0.8 years;BMI 30.3 ± 0.4 Kg/m2). Glycemia was assessed by glycated hemoglobin (A1c) level at the time of hospitalization. The severity of the COVID-19 outcome was assessed by quick sepsis-related organ failure assessment (qSOFA) and length of hospitalization was determined by the number of days spent in the hospital. Patients were categorized into normoglycemic (N: A1c <5.7%), prediabetes (Pre: 5.7% ≤ A1c < 6.5%), and diabetes mellitus (DM: A1c ≥ 6.5%) groups. DM group was further categorized for diabetes management with medication. One-way ANOVA and unpaired t-test were used to determine the statistical differences among/between groups as appropriate. Results: There was no significant difference among groups in severity of COVID-19 infection (qSOFA: N 0.24 ± 0.08, Pre 0.38 ± 0.07, D 0.28 ± 0.03;p>0.05) and length of hospitalization (N 5.6 ± 0.8, Pre 9.3 ± 1.0, DM 8.9 ± 0.6 days;p>0.05). However, patients with unmanaged diabetes (no medication) showed significantly greater severity (qSOFA: 0.44 ± 0.08 vs. 0.22 ± 0.03;p<0.05) and length of hospitalization (10.8 ± 1.6 vs. 8.2 ± 0.6 days;p<0.05) compared to patients who managed diabetes with medication. Conclusion: Unmanaged diabetes shows worsened severity and the rate of recovery in COVID-19 patients. Diabetes management should be considered in the treatment of COVID-19 patients.