Appearance and Prevalence of JN.1 SARS-CoV-2 Variant in India and Its Clinical Profile in the State of Maharashtra.

BACKGROUND: In August 2023, the BA.2.86 SARS-CoV-2 variant, with over 30 spike protein mutations, emerged amidst the global dominance of XBB sub-lineages. It evolved into JN.1 by late 2023, spreading across 71 countries. JN.1, distinct for its L455S mutation, significantly dominated global sequences, raising concerns over its transmission and clinical impact. The study investigates JN.1's clinical severity and its effect on hospital admissions in Maharashtra, India. METHODOLOGY: The present study involved 3,150 curated Indian SARS-CoV-2 whole genome sequences with collection dates between 1st August 2023 and 15th January 2024. Lineage and phylogenetic analysis of sequences was performed using Nextclade. Telephonic interviews were conducted to confirm the demographic details and obtain clinical information on the JN.1* (* indicates JN.1 and all its sub-lineages) cases. The obtained data were recorded and analyzed using Microsoft® Excel (Microsoft Corporation, Redmond, WA). RESULTS: Out of 3,150 sequences analyzed, JN.1* was the most common lineage (2377/3150, 75.46%), followed by XBB.2.3* (281/3150, 8.92%) and XBB.1.16* (187/3150, 5.94%). In India, it was first identified on 6th October 2023, in Kerala. The highest proportion of JN.1* sequences originated from Maharashtra (628/2377, 26.42%), followed by West Bengal (320/2377, 13.46%), Andhra Pradesh (293/2377, 12.33%), Kerala (288/2377, 12.12%), and Karnataka (285/2377, 11.99%). In Maharashtra, the JN.1* variant was first identified on 23rd November 2023. A total of 279 JN.1* cases were included in the clinical study. Of these, 95.34% (266/279) had symptomatic disease with mild symptoms; cold (187/279, 67.03%) being the most common symptom, followed by fever (156/279, 55.91%), cough (114/279, 40.86%), and headache (28/279, 15.64%). Of all the cases, 13.26% (37/279) required institutional quarantine or hospitalization, and the rest were isolated at home. Among the hospitalized patients, 54.05% (20/37) cases were given conservative treatment while 45.95% (17/37) cases required supplemental oxygen therapy. Regarding the vaccination status, 94.26% (263/279) of cases received at least one dose of the COVID-19 vaccine, while 5.02% (14/279) were not vaccinated, of which most were children aged zero to nine years (5/14, 35.71%). The overall recovery rate among JN.1* cases was 98.57% (275/279), with 1.43% (4/279) cases succumbing to the disease. CONCLUSION: The JN.1* variant, the dominant variant in India, exhibits clinical features similar to previous circulating variants in Maharashtra without increased severity. Its notable transmissibility underscores the importance of studying the ongoing viral evolution. The pressing necessity for swift identification and the clinical features of new variants is essential for effective public health response.

Genomic Characterization of an Emerging SARS-CoV-2 Variant During the Early Second Wave of the SARS-CoV-2 Pandemic in Maharashtra, India.

Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global health crisis, with various variants emerging over time. In India, particularly in Maharashtra, a resurgence of cases and distinct transmission patterns have been observed. This study aimed to identify and characterize the circulating SARS-CoV-2 variants during the early second wave in Maharashtra, India. Materials and methods Nasopharyngeal swabs were collected from 24 RT-PCR-positive coronavirus disease of 2019 (COVID-19) cases across four districts of Maharashtra. Whole genome sequencing (WGS) was performed using the ARTIC amplicon sequencing protocol, and the data were analyzed. Results A total of 189 amino-acid mutations were identified across the 24 samples. Compared to the Indian genomes, 44 amino-acid mutations were unique to 24 genomes. Clade 20A was the most prevalent (66.66%), followed by 20B and 21B. The lineage B.1.36 (45.83%) was the most common, followed by B.1.617.1 (16.67%). The D614G mutation was the most frequent spike mutation (95.83%). Four samples from the Amravati district clustered distinctly under Clade 21B with spike mutations E154K in the N-terminal domain (NTD), L452R and E484Q in the receptor-binding domain (RBD) and P681R in proximity to the furin cleavage site. The temporal distribution of samples revealed the presence of Clade 21B in Maharashtra since the 31st of January 2021. Conclusion The study provides valuable insights into the circulating SARS-CoV-2 variants during the early second wave in Maharashtra, highlighting specific clades and mutations. The unique clustering patterns and the high prevalence of immune-escape mutations emphasize the need for continuous monitoring and genomic surveillance.

Trend analysis in seroprevalence of dengue, chikungunya and malaria: A seven-year serological study from a tertiary care hospital of Maharashtra, India.

BACKGROUND & OBJECTIVES: Dengue, chikungunya and malaria are mosquito-borne infections, which have shared endemicity and similar clinical presentation. Simultaneous co-infection with more than one infectious agent complicates the diagnosis and further course of treatment. This study aims to determine the seroprevalence and trend of malaria, dengue and chikungunya from 2014-2020 in a tertiary care hospital of western India. METHODS: The present study was retrospective descriptive record-based. Serum samples from clinically suspected dengue and chikungunya were subjected to both IgM antibody capture ELISA kits produced by National Institute of Virology (NIV), Pune, India. They were also subjected to ELISA based NS1Ag testing. In Suspected malaria cases, blood collected in EDTA tubes was subjected for Rapid Malaria antigen testing. Statistical analysis was performed using MS Excel and JMP Software. RESULTS: Seropositivity of malaria was comparatively higher in 2014 (5.53%) and a decreasing trend was observed in subsequent years. Majority of malarial infections were caused by Plasmodium vivax (81.67%). There is drastic increase in seropositivity of chikungunya from 2016 (23.67%) and thereafter as compared to 2014 (6.57%) and 2015 (7.29%) indicating its re-emergence. The dengue seropositivity in 2019 (40.19%) was highest in last seven years. Males were predominantly affected, and most affected age group was 21-30 years. Peak transmission was observed in post-monsoon seasons. Dengue and chikungunya co-infection was observed to be 5.79%. INTERPRETATION & CONCLUSION: This study emphasizes the importance of surveillance studies to understand the trend of vector-borne diseases for prompt diagnosis, management of patients in hospital setup and for early detection and curtailment of outbreaks and epidemics by public health sectors through appropriate vector control programs.

Clinical Characteristics of SARS-CoV-2 Omicron Cases in Pune, Maharashtra, India.

Background The SARS-CoV-2 Omicron variant, within two months of its detection, replaced the Delta variant to become the dominant circulating variant globally. Therefore, it is essential to understand the characteristics of the disease caused by the variant and its impact on vaccination. Methods A total of 165 confirmed Omicron cases attending a tertiary care hospital in Pune, Maharashtra, between December 2021 to February 2022 were studied. Their demographic, clinical, and immunization history was recorded. Results Among the 165 cases, 7.88% were B.1.1.529 Omicron cases, 25.45% were BA.1 Omicron cases, and 66.67% were BA.2 Omicron cases. Of these 165 patients, 146 (88.48%) were discharged after treatment, 12 (7.27%) died during hospitalization, and seven (4.24%) were brought dead. The presence of one or more comorbid conditions was seen in 15.15%, of which diabetes mellitus and hypertension (28% each) were the most common conditions. Older age (greater than 60 years), an important risk factor for poor outcomes, was present in 9.1% of cases. Among the 165 cases, vaccination with at least one dose of vaccine was found in 80.61% of cases. Out of 165 cases, clinical data was available for 158 cases. Of these 158 cases, 86.71% had symptoms, and 13.29% were asymptomatic. Fever, followed by cough, myalgia, runny nose, and headache, were the most common presenting symptoms. The mean duration of illness was 2.69 days, with 91.14% of cases having the illness for less than five days, and 89.24% of cases had a National Early Warning Score (NEWS) of 1-4, suggesting a good prognosis. In 93.90% of cases, the chest X-ray findings were normal. Of the 158 cases, 92.41% of cases recovered with supportive treatment, and only 7.59% of cases required oxygen therapy. Conclusion The current study shows that the Omicron variant caused mild disease with reduced need for hospital admission and oxygen therapy in India.

An Early and Preliminary Assessment of the Clinical Severity of the Emerging SARS-CoV-2 Omicron Variants in Maharashtra, India.

BACKGROUND: The SARS-CoV-2 Omicron variants BA.2.74, BA.2.75, and BA.2.76 have appeared recently in India and have already spread to over 40 countries. They have acquired additional mutations in their spike protein compared to BA.2, branching away on the SARS-CoV-2 phylogenetic tree. These added mutations have raised concerns about the impact on viral pathogenicity, transmissibility, and immune evasion properties of the new variants. MATERIAL AND METHODS: A total of 990 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) positive SARS-CoV-2 samples, with a cycle threshold value (Ct) less than 25, were processed for SARS-CoV-2 whole genome sequencing between June 3, 2022 to August 7, 2022. All corresponding demographic and clinical data were recorded and analyzed using Microsoft® Excel. RESULTS: Out of 990 samples sequenced, BA.2.75 (23.03%) was the predominant Omicron sublineage, followed by BA.2.38 (21.01%), BA.5 (9.70%), BA.2 (9.09%), BA.2.74 (8.89%) and BA.2.76 (5.56%). A total of 228 cases of BA.2.74, BA.2.75, and BA.2.76 were contacted by telephone, of which 215 (94.30%) were symptomatic with mild symptoms, and 13 (5.70%) had no symptoms. Fever (82.02%) was the most common symptom, followed by cough (49.12%), cold (35.97%), fatigue (27.19%), headache (21.05%), and myalgia (20.61%). Of the 228 cases, 195 (85.53%) cases recovered at home, and 33 (14.47%) required institutional quarantine. Recovery with conservative treatment was observed in 92.98% of cases, while 4.83% required additional oxygen therapy. Only three (1.32%) cases had poor outcomes resulting in death, and the remaining 225 (98.68%) survived. Among the 228 cases, 219 (96.05%) cases were vaccinated with the COVID-19 vaccine; of these, 72.60% had received both doses, 26.03% had also received the precautionary booster dose, while 1.37% were incompletely vaccinated with a single dose of vaccine. CONCLUSION: The current study indicates that the three BA.2 sublineages are causing mild disease in India. However, BA.2.75 has key mutations that are notable for accelerated growth and transmission and require close and effective monitoring.

High-altitude pulmonary oedema: Newer treatment modalities for an age-old problem.

Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE. Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy. Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two. Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.

Anthropometric evaluation of school-going native highlanders (4-19 years of age) from the Leh-Ladakh region in India.

BACKGROUND: The native population of the Ladakh region faces the unique challenges of a high-altitude environment with distinct physiological adaptations in comparison with lowlanders. However, no comprehensive data on standard anthropometric parameters for the school-going children in this populace is available. OBJECTIVES: We aimed to study the various anthropometric parameters in the school-going native highlander population and computed measures of central tendency. The nutritional status of the community was also be determined by comparing with World Health Organization (WHO) scores for height for age (HFA), weight for age (WFA) and body mass index (BMI) for age. DESIGN: A cross-sectional, descriptive study was devised to assess the anthropometric parameters. We measured height, weight, mid-upper circumference (MUAC), triceps skinfold (TSF) thickness, sub-scapular skinfold (SSF) thickness, waist, hip and abdominal circumference. Statistical analysis was conducted to determine the mean [±2 standard deviation (SD)], median, range, minimum and maximum. The z-scores for HFA, WFA and BMI for age was computed using WHO reference data. SUBJECTS: A total of 346 school-going native highlander children (4-19 years of age) were studied. RESULTS: Among the study population, the mean height was 141.17 ± 39.08 cm, the mean weight was 38.27 ± 25.40 kg. The gender difference in height, MUAC, sub-scapular skinfold (SSF) thickness, TSF thickness and the abdominal circumference was found to be statistically significant. Of the subjects 23.46% were stunted (i.e. HFA below -2 SD of the WHO standard) and 7.01% were underweight (WFA below -2 SD of the WHO standard). CONCLUSION: The nutritional status of the Ladakhi population was assessed by comparison with the WHO reference data. Nomograms for anthropometric data in school-going children (4-19 years of age) of Ladakh were created. These can be used for further studies and planning targeted intervention strategies on this geographically isolated and evolutionary distinct highland population.

Hematological Parameters in Native Highlanders of Ladakh Aged 4-19 Years.

Hematological adaptations to high altitude (HA) are long studied but are focused either on lowlanders visiting HA or native highlanders from Andes and Tibet. The literature on native highlanders from the Indian subcontinent or paediatric highlanders is scarce. We aimed at assessing hematological parameters in native highlanders of Ladakh, India, aged 4-19 years and derive nomograms in an age stratified manner specific to these native highlanders. A total of 335 self-reported healthy native highlanders of Ladakh, without any known comorbidities and not on hematinic nor any drugs in the age group of 4-19 years were included in the study. Complete hemogram including red cell indices was measured. R ver 3.4.0 was used to compare the hematological parameters based on gender/age stratification, pubertal and nutritional status. The hematological reference ranges were created for various parameters in the paediatric population. The mean (SD) haemoglobin (Hb) concentration was 14.74 (2.07) gm/dL. The mean hematocrit (Hct) was 40.43 (5.57%) %, mean corpuscular volume (MCV) was 81.87 (7.22) fL, white blood cell (WBC) count was 7596 (2172) cells/µL and platelets was 378.4 (152.8) × 103/µL. Hct and MCV increased with age. Hb concentration, Hct, and MCV in girls was significantly lower than boys. Severely underweight subjects (body mass index < 16) showed significantly higher platelet counts compared to their nourished counterparts. The hematological nomograms for the native paediatric highlanders from Ladakh, India have been reported in this study.

Bedside Ultrasonography as an Alternative to Computed Tomography Scan for the Measurement of Optic Nerve Sheath Diameter.

BACKGROUND: Optic nerve sheath diameter (ONSD) as measured by optic nerve sheath ultrasonography (ONSU) is used as a surrogate marker of intracranial pressure (ICP), especially in resource-limited settings. There is a growing interest in the use of ONSU in emergency and high-altitude setups. Notwithstanding multiple studies done on this subject, there is a paucity of data regarding standardization of techniques and comparison of ONSU with computed tomography (CT). MATERIALS AND METHODS: Thirty-five patients with a diagnosis of high-altitude cerebral edema were enrolled in the study. ONSD was measured in all patients using ONSU, along visual and coronal axis, and CT scan. We repeated ONSU in these patients on days 3, 7, 10, and 15 (day of discharge). Correlation between visual and coronal axis as well as CT scan was analyzed. RESULTS: The correlation of visual to coronal and coronal to visual was equally significant (both correlation coefficients being R2 = 0.983). Correlation of ONSD by visual axis to CT scan was better than coronal axis (correlation coefficient R2 = 0.986 vs. 0.96, respectively). CONCLUSION: In our study, we found a strong correlation between the visual and coronal axes. Thus, either of the two axes can be used for monitoring ICP. However, it has been found that measurements along the coronal axis are challenging, especially in the emergency setup. ONSD measured along visual axis correlated better with CT scan as compared to the coronal axis.

Comparison of Optic Nerve Sheath Diameter between both eyes: A Bedside Ultrasonography Approach.

CONTEXT: Optic nerve sheath diameter (ONSD) has long been accepted as a reliable proxy of intracranial pressure especially in critical care and bedside settings. The present consensus is to measure ONSD in both eyes and take average value, which is cumbersome and a potential cause of discomfort to the patient. AIM: We aim to compare the values of ONSD of the right and left eye in a random sample as measured by bedside ocular ultrasonography (USG) in Indian adults. SETTINGS AND DESIGN: This was a prospective study conducted from September 2012 to March 2013 in the Department of Internal Medicine of a tertiary care hospital situated at moderate high altitude (11,500 ft) in India. MATERIALS AND METHODS: Patients admitted with high altitude pulmonary edema (HAPE) were recruited by convenience sampling. The ONSD of both eyes were measured 3 mm behind the globe using a 7.5 MHz linear probe on the closed eyelids of supine subjects. STATISTICAL ANALYSIS: Analysis was done using SPSS 17.0. RESULTS: A total of 47 patients of HAPE were recruited to the study with daily ONSD recording of both eyes during the admission period. The mean ONSD of the left eye was 4.60 (standard deviation [SD] = 0.71) whereas the mean ONSD of right eye 4.59 (SD = 0.72). The ONSD of the right eye and left eye was strongly correlated (correlation coefficient = 0.98 with P < 0.0001). The mean difference in the ONSD of both eyes (right-left) was -0.0044 (SD = 0.11) which was not statistically significant (P = 0.533). CONCLUSION: Our results suggest that the difference in ONSD of both eyes is not statistically significant in disease or health. This study also suggests that the ONSD of either eye can be predicted by the other eye recordings. Based on these findings, it can be suggested that during ocular USG for routine bedside/research purposes it is sufficient to measure ONSD of any of the one eye to save time and avoid discomfort to the patient.

Endothelial markers in high altitude induced systemic hypertension (HASH) at moderate high altitude.

BACKGROUND: Chronic intermittent hypoxia is known to induce systemic arterial hypertension whereas chronic hypoxia causes pulmonary arterial hypertension. High altitude (HA) induced systemic hypertension (HASH) in previously normotensive lowlanders following acclimatisation and prolonged stay at moderate HA is a commonly encountered medical problem. HASH has been attributed to increased sympathetic discharge. Endothelial dysfunction (ED) is implicated in hypertension in the plains hence this study was conducted in HA. This is relevant especially because of the established role of ED in the aetiopathogenesis of HA illnesses. Since hypoxia may induce ED, we aimed at studying the association of endothelial dysfunction with HASH in temporary residents at HA. METHODS: In this case-control single-centre study, we evaluated ED, by measuring endothelial molecular markers, soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF) and endothelial selectin (E-Selectin) in 24 cases with HASH and 25 age, sex matched normotensive controls at moderate high altitude (11,500 ft). RESULTS: The levels of sICAM-1 (patients: 214.3 ± 34.2 µg/L, controls: 196.2 ± 28.5 µg/L; p = 0.049) and VCAM-1 (patients 766.1 ± 123.4 ng/mL, controls: 668.6 + 117.6 ng/mL; p = 0.007) were statistically higher in the patient group. However, VEGF and E-Selectin were not significantly different between the groups. sICAM-1 significantly correlated with levels of systolic and diastolic blood pressure (r = 0.401, p = 0.003 and 0.486, p = 0.000) respectively. CONCLUSION: HASH is associated with endothelial dysfunction in form of raised levels of sICAM-1 and VCAM-1.

Managing High-Altitude Pulmonary Edema with Oxygen Alone: Results of a Randomized Controlled Trial.

Yanamandra, Uday, Velu Nair, Surinderpal Singh, Amul Gupta, Deepak Mulajkar, Sushma Yanamandra, Konchok Norgais, Ruchira Mukherjee, Vikrant Singh, Srinivasa A. Bhattachar, Sagarika Patyal, and Rajan Grewal. High-altitude pulmonary edema management: Is anything other than oxygen required? Results of a randomized controlled trial. High Alt Med Biol. 17:294-299, 2016.-Treatment strategies for management of high-altitude pulmonary edema (HAPE) are mainly based on the observational studies with only two randomized controlled trials, thus the practice is very heterogeneous and individualized as per the choice of treating physician. To compare the response to different modalities of therapy in patients with HAPE in a randomized controlled manner. We conducted an open-label, randomized noninferiority trial to compare three modalities of therapy (Therapy 1: supplemental O2 with oral dexamethasone 8 mg q8 hours [n = 42], Therapy 2: supplemental O2 with sustained release oral nifedipine 20 mg q8 hours [n = 41], and Therapy 3: only supplemental O2 [n = 50]). Bed rest was mandated in all patients. The study was conducted in a cohort of previously healthy young lowlander males at an altitude of 3500 m. Baseline characteristics of the patients were comparable in the study arms. Complete response was defined as clinical and radiological resolution of features of HAPE, no oxygen dependency, a normal 6-minute walk test (6MWT) on 2 consecutive days, and normal two-dimensional echocardiography. Results were compared by analysis of variance using SPSS version 16.0. There was no statistical difference in duration of therapy to complete response between the three groups (Therapy 1: 8.1 ± 4.0 days, Therapy 2: 6.7 ± 3.9 days, Therapy 3: 6.8 ± 3.2 days; p = 0.15). There were no deaths in any of the groups. We conclude that oxygen and bed rest alone are adequate therapy for HAPE and that adjuvant pharmacotherapy with either dexamethasone or nifedipine does not hasten recovery.