Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals.

Cytokines are major players in orchestrating inflammation, disease pathogenesis, and severity during COVID-19. Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses to various inflammatory and infectious diseases. However, the role of the IL-10 family of cytokines in COVID-19 remains elusive. Hence, we determined the plasma levels of the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, and IL-24) in 7 groups of COVID-19 individuals, based on days since real-time reverse transcriptase-polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data show that the levels of IL-10, IL-19, IL-20, IL-22, and IL-24 cytokines decreased from days 15-30 to days 61-90 and plateaued thereafter. Severe COVID-19 patients exhibit increased plasma levels of IL-10, IL-19, IL-20, IL-22, and IL-24 compared to mild patients. Thus, our study provides evidence of alterations in the plasma levels of the IL-10 family of cytokines in convalescent COVID-19 individuals.

The association between body mass index, abdominal fatness, and weight change and the risk of adult asthma: a systematic review and meta-analysis of cohort studies.

Obesity has been associated with increased risk of adult asthma, however, not all studies have found a clear association between overweight and the incidence of asthma, and data on other adiposity measures have been limited. Hence, we aimed to summarize evidence on association between adiposity and adult asthma. Relevant studies were retrieved through searches conducted in PubMed, and EMBASE up to March 2021. A total of sixteen studies (63,952 cases and 1,161,169 participants) were included in the quantitative synthesis. The summary RR was 1.32 (95% CI 1.21-1.44, I2 = 94.6%, pheterogeneity < 0.0001, n = 13) per 5 kg/m2 increase in BMI, 1.26 (95% CI 1.09-1.46, I2 = 88.6%, pheterogeneity < 0.0001, n = 5) per 10 cm increase in waist circumference and 1.33 (95% CI 1.22-1.44, I2 = 62.3%, pheterogeneity= 0.05, n = 4) per 10 kg increase in weight gain. Although the test for nonlinearity was significant for BMI (pnonlinearity < 0.00001), weight change (pnonlinearity = 0.002), and waist circumference (pnonlinearity = 0.02), there was a clear dose-response relationship between higher levels of adiposity and asthma risk. The magnitude of the associations and the consistency of the results across studies and adiposity measures provide strong evidence that overweight and obesity, waist circumference and weight gain increases asthma risk. These findings support policies to curb the global epidemic of overweight and obesity.

Litchi consumption and missed meals continue to be associated with acute encephalopathy syndrome among children: an investigation of the 2019 outbreak in Muzaffarpur district, Bihar, India.

BACKGROUND: Muzaffarpur district in Bihar State of India recorded a resurgence of acute encephalopathy syndrome (AES) cases in the summer of 2019 after no reported outbreak in 3 y. Earlier studies generated evidence that litchi consumption and missing the previous evening's meal were associated with AES. We investigated the recent outbreak to understand the risk factors associated with AES. METHODS: We conducted a matched case-control study by comparing AES cases with healthy controls from case-households and the neighborhood community for risk factors like missing evening meal and litchi consumption before onset of AES. RESULTS: We recruited 61 cases and 239 controls. Compared with the community controls, case-patients were five times more likely to have reported eating litchi in the 7 d preceding the onset of illness (adjusted OR [AOR]=5.1; 95% CI 1.3 to 19) and skipping the previous evening's meal (AOR=5.2; 95% CI 1.4 to 20). Compared with household controls, case-patients were five times more likely to be children aged <5 y (AOR=5.3; 95% CI 1.3 to 22) and seven times more likely to have skipped the previous evening's meal (AOR=7.4; 95% CI 1.7 to 34). CONCLUSIONS: Skipping the previous evening's meal and litchi consumption were significantly associated with AES among children in Muzaffarpur and adjoining districts of Bihar.

Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015-2020.

OBJECTIVES: We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India. DESIGN: A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data. SETTING: National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status. PARTICIPANTS: Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district. OUTCOME MEASURES: We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015. RESULTS: The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra. CONCLUSION: TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

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.

COVID-19 testing, timeliness and positivity from ICMR's laboratory surveillance network in India: Profile of 176 million individuals tested and 188 million tests, March 2020 to January 2021.

BACKGROUND: The Indian Council of Medical Research set up a pan-national laboratory network to diagnose and monitor Coronavirus disease 2019 (COVID-19). Based on these data, we describe the epidemiology of the pandemic at national and sub-national levels and the performance of the laboratory network. METHODS: We included surveillance data for individuals tested and the number of tests from March 2020 to January 2021. We calculated the incidence of COVID-19 by age, gender and state and tests per 100,000 population, the proportion of symptomatic individuals among those tested, the proportion of repeat tests and test positivity. We computed median (Interquartile range-IQR) days needed for selected surveillance activities to describe timeliness. RESULTS: The analysis included 176 million individuals and 188 million tests. The overall incidence of COVID-19 was 0.8%, and 12,584 persons per 100,000 population were tested. 6.1% of individuals tested returned a positive result. Ten of the 37 Indian States and Union Territories accounted for about 75.6% of the total cases. Daily testing scaled up from 40,000 initially to nearly one million in March 2021. The median duration between symptom onset and sample collection was two (IQR = 0,3) days, median duration between both sample collection and testing and between testing and data entry were less than or equal to one day. Missing or invalid entries ranged from 0.01% for age to 0.7% for test outcome. CONCLUSION: The laboratory network set-up by ICMR was scaled up massively over a short period, which enabled testing a large section of the population. Although all states and territories were affected, most cases were concentrated in a few large states. Timeliness between the various surveillance activities was acceptable, indicating good responsiveness of the surveillance system.

Age- & sex-specific infection fatality ratios for COVID-19 estimated from two serially conducted community-based serosurveys, Chennai, India, 2020.

Background & objectives: Infection fatality ratio (IFR) is considered a more robust and reliable indicator than case fatality ratio for severity of SARS-CoV-2 infection. Age- and sex-stratified IFRs are crucial to guide public health response. Infections estimated through representative community-based serosurveys would gauge more accurate IFRs than through modelling studies. We describe age- and sex-stratified IFR for COVID-19 estimated through serosurveys conducted in Chennai, India. Methods: Two community-based serosurveys were conducted among individuals aged ≥10 yr during July and October 2020 in 51 of the 200 wards spread across 15 zones of Chennai. Total number of SARS-CoV-2 infections were estimated by multiplying the total population of the city aged ≥10 yr with the weighted seroprevalence and IFR was calculated by dividing the number of deaths with the estimated number of infections. Results: IFR was 17.3 [95% confidence interval (CI): 14.1-21.6] and 16.6 (95% CI: 13.8-20.2) deaths/10,000 infections during July and October 2020, respectively. Individuals aged 10-19 years had the lowest IFR [first serosurvey (R1): 0.2/10,000, 95% CI: 0.2-0.3 and second serosurvey (R2): 0.2/10,000, 95% CI: 0.1-0.2], and it increased with age and was highest among individuals aged above 60 yr (R1: 140.0/10,000, 95% CI: 107.0-183.8 and R2: 111.2/10,000, 95% CI: 89.2-142.0). Interpretation & conclusions: Our findings suggested that the IFR increased with age and was high among the elderly. Therefore, elderly population need to be prioritized for public health interventions including vaccination, frequent testing in long-term care facilities and old age homes, close clinical monitoring of the infected and promoting strict adherence to non-pharmaceutical interventions.

Effectiveness of Presumptive Treatment of Acute Febrile Illness With Doxycycline or Azithromycin in Preventing Acute Encephalitis Syndrome in Gorakhpur, India: A Cohort Study.

OBJECTIVE: To estimate effectiveness of presumptive doxycycline or azithromycin treatment in preventing progression of Acute Febrile Illness to Acute Encephalitis Syndrome in Gorakhpur. STUDY DESIGN: Prospective cohort study. STUDY SETTING: Primary healthcare centers and Community healthcare centers of Gorakhpur district, Uttar Pradesh. PARTICIPANTS: Children aged 1 year to less than 15 years with fever of 3 days to less than 15 days duration attending three selected peripheral health facilities in Gorakhpur during August to October, 2018. PROCEDURE: 35 medical officers in three selected Primary Healthcare Centers/Community Healthcare centers were sensitized on the treatment strategy. After sensitization, study participants were enrolled and information about prescription of doxycycline or azithromycin was collected. Participants were telephonically followed-up to know their progression status from AFI to AES. MAIN OUTCOME MEASURE: Incidence of acute encephalitis syndrome among acute failure illness patients who received presumptive doxycycline or azithromycin treatment and those who did not receive this treatment. RESULTS: Of the enrolled 930 AFI patients, 801 (86%) were prescribed doxycycline or azithromycin and 725 (78%) could be telephonically followed-up. Progression to acute encephalitis syndrome was seen in 6 of the 621 patients who received presumptive treatment, and 5 of the 104 who did not receive the treatment. The relative risk of developing acute encephalitis syndrome among acute febrile illness patients who were prescribed presumptive treatment with doxycycline or azithromycin was 0.20 (95% CI: 0.06-0.65). The effectiveness of presumptive treatment with doxycycline or azithromycin strategy was 79.9% (95% CI: 35.4-94). CONCLUSIONS: PDA treatment to children presenting with fever in peripheral health facilities of the study blocks in Gorakhpur during August-November, 2018 had good effectiveness in preventing progression of acute febrile illness to acute encephalitis syndrome.