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Background & Objectives: COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529) has been reported. We conducted a study to describe the epidemiological and clinical characteristics and outcomes of COVID-19 patients with 'S' gene target failure (SGTF, suspected Omicron). Furthermore, their clinical outcomes with COVID-19 patients with non-SGTF (non-Omicron) were also compared., Methods: This study was conducted in Tamil Nadu, India, between December 14, 2021 and January 7, 2022 among patients who underwent reverse transcription-PCR testing for SARS-CoV-2 in four laboratories with facilities for S gene screening. Consecutively selected COVID-19 patients with SGTF were telephonically contacted, seven and 14 days respectively after their date of positive result to collect information on the socio-demographic characteristics, previous history of COVID-19, vaccination status and clinical course of illness along with treatment details. To compare their outcomes with non-SGTF patients, one randomly suspected non-Omicron case for every two suspected Omicron cases from the line-list were selected, matching for the date of sample collection and the testing laboratory., Results: A total of 1175 SGTF COVID-19 patients were enrolled for this study. Almost 6 per cent (n=72) reported a history of previous infection. 141 (13.5%) suspected Omicron cases were non-vaccinated, while 148 (14.2%) and 703 (67.4%) had received valid one and two doses of COVID-19 vaccines, respectively. Predominant symptoms reported included fever (n=508, 43.2%), body pain (n=275, 23.4%), running nose (n=261, 22.2%) and cough (n=249, 21.2%). Five (0.4%) of the 1175 suspected Omicron cases required oxygen supplementation as compared to ten (1.6%) of the 634 suspected non-Omicron cases. No deaths were reported among omicron suspects, whereas there were four deaths among suspected non-Omicron cases., Interpretation & Conclusions: Majority of the suspected Omicron cases had a mild course of illness. The overall severity of these cases was less compared to the suspected non-Omicron cases.

Blood collection using dried blood spots (DBS) provides an easier alternative to venipuncture for sample collection, transport, and storage but requires additional processing that can cause variability in results. Whole-blood samples spotted on four DBS devices and respective paired serum samples were tested for antimeasles and antirubella IgG antibody concentrations by enzyme immunoassay. Elution protocols for DBS devices were optimized for comparability relative to serum samples using 12 adult volunteers. Stability of DBS collected on HemaSpot HF was assessed under various temperature conditions (+4, 22 to 25, and 45°C) at six time points (0, 7, 15, 30, 60, and 90 days) in a controlled laboratory setting using six adult volunteers. Devices were shipped and stored for 30 days at four settings with variable temperature and humidity conditions to assess the impact on antibody concentrations. Three DBS devices demonstrated comparable antibody concentrations with paired sera following optimization. Antibodies recovered from DBS were stable for at least 90 days at 4°C and for 30 days at ambient temperature (22 to 25°C) using the HemaSpot HF device. A drastic decline in antibody concentrations was observed at 45°C, resulting in quantitative and qualitative discrepancies by day 7. HemaSpot HF devices shipped to field sites and stored at ambient temperature and humidity resulted in quantitative, but not qualitative, variability. Measurement of antimeasles and antirubella IgG antibodies with DBS devices is an accurate alternative to testing serum, provided elution protocols are optimized. Stability of HemaSpot HF devices at ambient temperature enables broader use in surveys when serum processing and cold storage are not feasible. IMPORTANCE Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. We optimized a protocol to elute IgG antibodies against measles and rubella viruses in four DBS devices, demonstrating high concordance with paired venous sera for most devices. Extensive stability studies with various temperature and storage conditions in the laboratory and in the field were conducted using HemaSpot HF DBS devices prior to its use in one of the largest community-based measles and rubella serological surveys in the world.

Fingerprick blood spotted onto filter paper offers an alternative to venous blood for use in population-based surveillance because it is comparatively inexpensive, acceptable, and easy to manage in the field. Prior studies have shown excellent agreement for immunoglobulin G (IgG) antibody detection from dried blood spots (DBS) and venous blood samples. However, much of this evidence is from high-income settings or laboratories where the samples were unlikely to be exposed to extreme temperatures and humidity, factors known to degrade DBS. We report the diagnostic accuracy of DBS collected using HemaSpot HF devices against venous sera in measuring measles- and rubella-specific IgG antibodies in a household serosurvey conducted in two districts in India. Paired serum and DBS samples collected by fingerprick were collected from women aged 15 to 50 years enrolled in a serosurvey in Palghar District of Maharashtra and Kanpur Nagar District of Uttar Pradesh in India. Specimen quality and volume were assessed in the laboratory. Samples were tested for antimeasles and antirubella IgG antibodies by an enzyme-linked immunosorbent assay (ELISA) (Euroimmun). Sensitivity of antibody detection by DBS was greater than 98%, and specificity was 90% and 98%, for measles and rubella IgG, respectively. Antibody concentrations were strongly correlated between paired specimens with adequate volume (measles R 2 = 0.94; rubella R 2 = 0.89). Although correlation was poor if DBS specimens had lower volumes, impact on qualitative results was minimal. This study showed DBS collected with HemaSpot HF devices can generate highly accurate results of measles- and rubella-specific IgG compared to sera in community-based surveys when protocols are optimized for DBS specimens. IMPORTANCE Dried blood spot (DBS) collection provides an easy, practical, and acceptable alternative to venous blood collection, especially for community-based studies, provided that results from DBS are accurate. We demonstrated high sensitivity and specificity for measles- and rubella-specific immunoglobulin G (IgG) with DBS collected via HemaSpot HF devices compared to serum samples. This is one of the largest community-based diagnostic accuracy studies of measles and rubella antibody testing with DBS and the first application we are aware of using HemaSpot HF device for measles and rubella serology. Results support the use of DBS in community-based serosurveillance.

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., Competing Interests: None

Gorakhpur division consisting of Gorakhpur and neighboring districts Deoria, Kushinagar and Maharajganj in Uttar Pradesh, India, have been witnessing seasonal outbreaks of acute encephalitis syndrome (AES) among children for the last three decades. Investigations conducted during 2005 identified Japanese encephalitis (JE) virus as an aetiology of AES. With the introduction of JE vaccination and other control strategies, the incidence of JE in the region declined, however, outbreaks of acute febrile illness with neurological manifestations continued to occur. Subsequent investigations identified Orientia tsutsugamushi, as the major aetiology of AES outbreaks in the region. This review details clinical, epidemiological, animal and entomological investigations conducted for AES due to O. tsutsugamushi during 2015 and 2017 in Gorakhpur region. Surveillance of acute febrile illness among children attending peripheral health facilities identified scrub typhus as an important aetiology of febrile illness during monsoon and post-monsoon months. Population-based serosurveys indicated high endemicity of scrub typhus. Entomological studies demonstrated natural infection of O. tsutsugamushi in small animal hosts and vector mites. Children acquired this infection through recent exposure to outdoor environment, while playing, or visiting fields or defecating in open fields. A few of the children with scrub typhus progress to develop CNS manifestations. Hence, early administration of appropriate antibiotics is crucial in preventing progression of AFI due to scrub typhus to AES. The investigations conducted by the multi-disciplinary team helped understand the transmission dynamics of scrub typhus in Gorakhpur division and recommend strategies for its control., Competing Interests: None

Globally, India has reported the third highest number of COVID-19 cases. Chennai, the capital of Tamil Nadu state, witnessed a huge surge in COVID-19 cases, resulting in the establishment of isolation facilities named COVID Care Center (CCC). In our study, we describe the demographic, epidemiological, and clinical characteristics; clinical progression; and outcome of 1,263 asymptomatic/mildly symptomatic COVID-19 patients isolated in one such CCC between May 4, 2020 and June 4, 2020. Around 10.5% of the patients progressed to moderate/severe illness, requiring referral for tertiary care, and three died. Nearly half (49.5%) of the patients were symptomatic at the time of admission, 2.2% of the patients developed symptoms post-testing, and 48.5% patients remained asymptomatic during the entire course of illness. Most common presenting symptoms were fever (69.9%) and cough (29.6%), followed by generalized body pain, breathlessness, and loss of smell and taste. On multivariate analysis, we identified that symptomatic patients with comorbidities and higher neutrophil-lymphocyte ratio (NLR) were more likely to progress to severe illness warranting referral for tertiary care. COVID Care Center ensured case isolation and monitoring of asymptomatic/mildly symptomatic patients, thereby providing hospital beds for sick patients. COVID Care Center isolation facilities are safe alternatives for medical institutions to isolate and monitor COVID-19 patients. Older symptomatic patients with comorbidities and a high NLR admitted in an isolation facility must be frequently monitored for prompt identification of clinical progression and referral to higher center for advanced medical care.

Background & Objectives: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India., Methods: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity., Results: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths., Interpretation & Conclusions: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country., Competing Interests: None

Conducting population-based serosurveillance for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) will estimate and monitor the trend of infection in the adult general population, determine the socio-demographic risk factors and delineate the geographical spread of the infection. For this purpose, a serial cross-sectional survey would be conducted with a sample size of 24,000 distributed equally across four strata of districts categorized on the basis of the incidence of reported cases of COVID-19. Sixty districts will be included in the survey. Simultaneously, the survey will be done in 10 high-burden hotspot cities. ELISA-based antibody tests would be used. Data collection will be done using a mobile-based application. Prevalence from the group of districts in each of the four strata will be pooled to estimate the population prevalence of COVID-19 infection, and similarly for the hotspot cities, after adjusting for demographic characteristics and antibody test performance. The total number of reported cases in the districts and hotspot cities will be adjusted using this seroprevalence to estimate the expected number of infected individuals in the area. Such serosurveys repeated at regular intervals can also guide containment measures in respective areas. State-specific context of disease burden, priorities and resources should guide the use of multifarious surveillance options for the current COVID-19 epidemic., Competing Interests: None

Background & Objectives: A cluster of SARS-CoV-2 infection occurred among Italian tourists visiting India. We report here the epidemiological, clinical, radiological and laboratory findings of the first cluster of SARS-CoV-2 infection among the tourists., Methods: Information was collected on demographic details, travel and exposure history, comorbidities, timelines of events, date of symptom onset and duration of hospitalization from the 16 Italian tourists and an Indian with laboratory-confirmed SARS-CoV-2 infection. The clinical, laboratory, radiologic and treatment data was abstracted from their medical records and all tourists were followed up till their recovery or discharge or death. Throat and deep nasal swab specimens were collected on days 3, 8, 15, 18, 23 and 25 to evaluate viral clearance., Results: A group of 23 Italian tourists reached New Delhi, India, on February 21, 2020 and along with three Indians visited several tourist places in Rajasthan. By March 3, 2020, 17 of the 26 (attack rate: 65.4%) had become positive for SARS-CoV-2 infection. Of these 17 patients, nine were symptomatic, while eight did not show any symptoms. Of the nine who developed symptoms, six were mild, one was severe and two were critically ill. The median duration between the day of confirmation for COVID-19 and RT-PCR negativity was 18 days (range: 12-23 days). Two patients died with a case fatality of 11.8 per cent., Interpretation & Conclusions: This study reconfirms higher rates of transmission among close contacts and therefore, public health measures such as physical distancing, personal hygiene and infection control measures are necessary to prevent transmission., Competing Interests: None

Background & Objectives: Sentinel surveillance among severe acute respiratory illness (SARI) patients can help identify the spread and extent of transmission of coronavirus disease 2019 (COVID-19). SARI surveillance was initiated in the early phase of the COVID-19 outbreak in India. We describe here the positivity for COVID-19 among SARI patients and their characteristics., Methods: SARI patients admitted at 41 sentinel sites from February 15, 2020 onwards were tested for COVID-19 by real-time reverse transcription-polymerase chain reaction, targeting E and RdRp genes of SARS-CoV-2. Data were extracted from Virus Research and Diagnostic Laboratory Network for analysis., Results: A total of 104 (1.8%) of the 5,911 SARI patients tested were positive for COVID-19. These cases were reported from 52 districts in 20 States/Union Territories. The COVID-19 positivity was higher among males and patients aged above 50 years. In all, 40 (39.2%) COVID-19 cases did not report any history of contact with a known case or international travel., Interpretation & Conclusions: COVID-19 containment activities need to be targeted in districts reporting COVID-19 cases among SARI patients. Intensifying sentinel surveillance for COVID-19 among SARI patients may be an efficient tool to effectively use resources towards containment and mitigation efforts., Competing Interests: None

Background: Seasonal outbreaks of acute encephalitis syndrome (AES) with high fatality have been occurring in Gorakhpur, Uttar Pradesh, India, for several years. We conducted investigations during the 2016 outbreak to identify the etiology., Methods: We included 407 hospitalized AES patients with cerebrospinal fluid pleocytosis (>5 cells/mm) in our study. These patients were clinically examined; their blood and cerebrospinal fluid samples were collected and investigated for scrub typhus (ST), Japanese encephalitis virus (JEV), dengue virus and spotted fever group of Rickettsia by serology and/or polymerase chain reaction., Results: Of the 407 AES patients, 266 (65.4%), 42 (10.3%) and 29 (7.1%) were diagnosed to have ST, JEV and dengue infection, respectively. Four patients were diagnosed to have spotted fever group of Rickettsia infection. A significantly higher proportion of ST patients with AES had hepatomegaly, splenomegaly and facial edema. The common hematologic and biochemical abnormalities among ST-positive patients include thrombocytopenia, raised liver enzymes and bilirubin levels. The case fatality ratio was significantly higher among ST-negative AES patients (36.2% vs. 15.2%; P < 0.05)., Conclusions: ST accounted for approximately two third of the AES case-patients. Efforts are required to identify the etiology of AES case-patients who are negative for ST, JEV and dengue fever.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high case fatality have been occurring in Gorakhpur division in Eastern Uttar Pradesh, India, for more than three decades. Japanese encephalitis virus (JEV) accounted for <10% of AES cases, while the etiology of the remaining cases remained largely unknown. Investigations conducted during the 2014 and 2015 outbreaks indicated Orientia tsutsugamushi (Haruo Hayashi 1920) (Norio Ogata 1929) Tamura et al. 1995 (Rickettsiales: Rickettsiaceae) as the etiology in about 60% of AES cases. Hospital-based surveillance studies indicated that about one-fifth of the patients with acute febrile illness were due to scrub typhus. Further studies are required to identify the etiology of about a third of AES cases that test negative for scrub typhus, JEV, or dengue.

Seasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi . Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.