Reinfection of COVID-19 among doctors at a tertiary care centre in Northern India: A report from a resource-limited setting.

Background and Aims: There is an increasing recognition of reinfection in coronavirus disease 2019 (COVID-19). We studied the reinfection of COVID-19 disease among doctors at a tertiary care centre in Northern India. Methods: All COVID-19 patients readmitted for COVID-19 disease after any duration with at least a positive Real time- polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 were included. Their clinical profile, vaccination status, outcome and Centre for disease control (CDC), Atlanta, USA reinfection criteria screening were recorded. Results: A total of 57 (0.53%) doctors were identified and 56 of them satisfied the CDC criteria. It included 13 (20.3%) females and 89.3% of cases were from clinical specialities; 98.2% of individuals had the first infection in 2020 and mean duration between 2 infections was 156.29 ± 76.02 (35-298) days. Duration between two episodes of the disease with more than 90 days apart was in 80.3% cases. One (1.8%) patient developed severe disease and two (3.6%) cases were of moderate severity. Symptoms were similar in both infections except significantly higher number of extra-respiratory complaints (2.2% vs. 9.1%). There were 37.5% cases who had received first dose of vaccination of any duration at the time of second infection. Nine (16.1%) and four (7.1%) patients with more than 4 weeks after the first and second dose of vaccination developed the second infection, respectively. Conclusion: Majority of reinfection were symptomatic and developed after 90 days and so majority followed CDC criteria. Breakthrough infections among vaccinated healthcare worker are real, and with sustained exposure to the virus, they should continue to use precaution including hand hygiene and mask in order to prevent reinfection.

Circulating Cell-Free DNA Level in Prediction of COVID-19 Severity and Mortality: Correlation of with Haematology and Serum Biochemical Parameters.

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the ß-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6-1258) as compared to MCOV-19 at 219.8 ng/ml (167.7-299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.

Determinants of stroke in patients with rhino cerebral mucormycosis seen during the second wave of COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Rhino cerebral mucormycosis is an uncommon opportunistic infection of the nasal sinuses and brain, and a group of saprophytic fungi causes it. During the second wave of COVID-19, India witnessed an unprecedented number of patients with rhino cerebral mucormycosis. Invasion of the cavernous sinus and occlusion of the internal carotid artery in many cases resulted in a stroke. The study aimed to assess the clinical and neuroimaging predictors of stroke in patients with rhino cerebral mucormycosis. We also evaluated the predictors of death in these patients at 90 days. METHODS: A prospective study was performed at a tertiary care centre in India between July 2021 and September 2021. We enrolled consecutive microbiologically confirmed patients of rhino cerebral mucormycosis. All patients underwent neuroimaging of the brain. Treatment comprised of anti-fungal drugs and endoscopic nasal/sinus debridement. We followed the patients for 90 days and assessed the predictors of stroke and mortality RESULTS: Forty-four patients with rhino cerebral mucormycosis were enrolled. At inclusion, in 24 patients, the RT-PCR test for SARS-COV-2 was negative. Diabetes mellitus was the most frequent (72.7 %) underlying risk factor; in most, diabetes mellitus was recently discovered. At inclusion or subsequent follow-up, stroke was seen in 11 (25 %) patients. Only seven patients had hemiparesis. Imaging revealed internal carotid artery occlusion in 17 (38.6 %) patients. Hypertension, corticosteroid use, and cavernous sinus thrombosis were independent predictors of stroke. Nine (20.5 %) died during follow-up, and stroke was an independent predictor of death. CONCLUSION: Stroke indicated poor prognosis among rhino cerebral mucormycosis patients encountered during the second wave of the COVID-19 epidemic.

Role of Serum Homocysteine, C-Reactive Protein (CRP), Uric Acid & Pro-Brain Natriuretic Peptide (Pro-BNP) in Predicting the Functional Outcome in Patients with Ischemic Stroke- A Prospective Observational Study from North India.

Ischemic Stroke is an acute and rapidly progressing neurological disease. Stroke is the second largest cause of global death (5.5 million) after ischemic heart disease. Numerous biomarkers have been identified and studied related to acute ischemic stroke but currently, none of the biomarkers are available for prognostication in such cases. In this study, we measured the levels of four widely available, rapidly measured biomarkers and evaluated their association with the functional outcome at discharge. MATERIAL: This was a prospective observational study conducted on 81 patients of acute ischemic stroke after obtaining informed consent. A detailed history was taken and clinical examination was done. Serum levels of homocysteine, uric acid, C-reactive protein (CRP), and Pro-brain natriuretic peptide (Pro-BNP) were measured at admission and their association with functional outcome using mRS (modified Rankin Scale) were analyzed. OBSERVATION: During the study period, 81 cases of acute ischemic stroke were evaluated; among them, 13 had a cardioembolic stroke. Ischemic stroke was more common in the older age group. The mean age was 49 ± 16.2 years. 61.7 % of patients were males. Diabetes Mellitus (45.7%), Hypertension (45.7%), CAD (8.6%), Dyslipidemia (27.2%), Smoking (37%), and alcohol intake (29.6 %) were some major risk factors. The average duration of hospital stay was 13.3 ± 7.5 days. 22 cases expired during the hospital stay. Mean serum levels of homocysteine, CRP, and Pro-BNP were higher than normal values (22.7 ± 16.3 umol/l; 59.5 ± 42.7 mg/dl; 1949 ± 3265.7 pg/ml). The mean serum uric acid level was 6.1 ± 3.3 mg/dl. A significant association between MRS score and serum homocysteine was found [p=0.007]. There was also a significant association between Pro-BNP levels and MRS score in patients with cardioembolic stroke (p=<0.001). CONCLUSION: Higher serum levels of homocysteine, CRP, and Pro-BNP are associated with a higher risk of acute ischemic stroke. Homocysteine level at admission can predict the poor outcome at discharge in patients of acute ischemic stroke. Pro-BNP levels can be used as a predictor of poor outcomes in cardioembolic stroke.

Differential expression of circulating microRNAs in serum: Potential biomarkers to track Japanese encephalitis virus infection.

Japanese encephalitis is one of the serious vector-borne viral encephalitis diseases found worldwide and poses a major threat to public health. Most Japanese encephalitis virus (JEV) infections are subclinical; only 1: 250 to 1:1000 infected persons develop clinical presentations. Delay in proper diagnosis of JE affects the timeliness of treatment initiation and increases the mortality rate in patients. Therefore, there is an extreme need to develop potential biomarkers, which might improve the diagnosis and can become the basis for development of new therapeutics. The microRNAs (miRNAs/or miRs) are small noncoding RNAs of 17-24 nucleotides that are known to regulate about 60% of human genes. Although miRNAs have been found to regulate various aspects of innate and adaptive immune responses, less information on circulating miRNAs in JE is known. The study of JEV infected human serum miRNAs will provide novel information for the diagnosis of JE as well as for the improvement of disease outcome. Total RNA, including miRNA, was extracted from serum followed by the complementary DNA (cDNA) synthesis by using sequence-specific primers. cDNA was amplified using target-specific TaqMan MicroRNA Assay. Real-time polymerase chain reaction data was normalized using both exogenous (cel-miR-39) and endogenous (hsa-miR-93) controls. We have found significantly altered expression of miR-155 and miR-21 in serum of JEV infected patients as compared to healthy controls, revealing their role as a a noninvasive biomarker in JE. A significant correlation between miRNAs and JE was observed that offers the basis for miRNAs to serve as a new component to develop possible therapeutic strategies for JE in near future.

Molecular characterisation of Hepatitis E virus isolates from north India.

PURPOSE: Hepatitis E virus (HEV) is responsible for >50% of acute viral hepatitis (AVH) in developing countries. It has 4 major genotypes and various subtypes which vary in geographical distribution, clinical manifestations and epidemiological patterns. This study was conducted to characterise HEV isolates from north India to study the effect of host and viral factors on HEV infection. METHODS: Serum samples collected from 536 AVH patients admitted to Department of Medicine, King George's Medical University, Lucknow from July 2016 to June 2017 were screened for anti HEV IgM, anti HAV IgM, HBsAg and anti HCV antibodies using commercial ELISA kits. Samples either positive for anti HEV IgM antibodies (n â€‹= â€‹204) or negative for all 4 hepatotropic viruses (n â€‹= â€‹37) were enrolled and tested by real time PCR for HEV RNA. HEV RNA positive samples with high viral load were further subjected to nested PCR for amplification of capsid gene. Sequencing and phylogenetic analysis were performed. HEV strains isolated from this study were deposited to GenBank under accession numbers MG571274 to MG571283. RESULTS: Anti HEV IgM positivity was observed among 38% clinically suspected AVH cases. HEV RNA was detected in 31.8% seropositive HEV cases and additional 3 seronegative cases. Males outnumbered females and the most affected age group was of young adults. Maximum number of cases were seen during the months of June to September. Phylogenetic analysis showed that HEV strains in our study belonged to genotype 1a. Mortality in HEV infected pregnant females was 23.5% as compared to 2.4% in non-pregnant females. Adverse fetal outcome was recorded in 51% of HEV infected pregnancies. CONCLUSIONS: HEV genotype 1a is prevalent in our setting. HEV during pregnancy is associated with adverse maternal and fetal outcome.

COVID-19 cases and their outcome among patients with uncommon co-existing illnesses: A lesson from Northern India.

Introduction: Newer coexisting conditions should be identified in order to modify newer risk factors. Aim was to identify patients with non-classical or less common coexisting conditions in patients infected of COVID 19. Method: Single centred study from June 2020 to May 2021 at a tertiary centre in North India. A preformed questionnaire was used to record clinical and laboratory parameters and to identify cases which are in addition to CDC list and Indian data. Results: 0.67% (46) cases out of 6832 patients were identified to have non-classical coexisting illness. It was divided into 2 groups-infections A (60.1%) and non-infections B (39.9%). Group A included-tuberculosis- pulmonary (14.3%) & extra pulmonary (32.9%), bacterial (25.0%) viral infections [dengue, hepatitis B & C] (14.3%), HIV disease (10.7%) and malaria (3.6%). Group B included- organ transplant (27.8%), autoimmune [myasthenia gravis, polymyositis, psoriasis] (22.6%), haematologic [Haemophilia, ITP, Aplastic anaemia, APML, CML] (27.8%), uncommon malignancies [disseminated sacral chordoma and GTN] (11.1%) and snakebite (11.1%). Serum Procalcitonin was not helpful for diagnosis of bacterial infection in COVID-19 disease. Group A had significantly longer duration of illness, hepatitis and elevated CRP. The mortality in group A & B were 32.1% and 43.8% respectively. Death in non-severe COVID cases was in tetanus and snakebite. 30.7% death among tuberculosis patients. More than 70% of deaths were attributable to COVID 19 in both the groups. Conclusion: In Indian settings, comorbidities like tuberculosis and bacterial infections can precipitate severe COVID 19 unlike other parts of the world where tuberculosis is relatively uncommon.

Prevalence of Dengue, Chikungunya, and Zika Viruses in Febrile Pregnant Women: An Observational Study at a Tertiary Care Hospital in North India.

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29-21.30) and mortality (OR = 19.0, 95% CI = 1.01-357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

Clinical and biochemical profile of scrub typhus patients at a tertiary care hospital in Northern India.

BACKGROUND: Scrub typhus is a neglected rickettsial disease in India. Every year, we are facing outbreaks of Scrub typhus after Monsoon season. Patients present with a wide clinical spectrum ranging from pyrexia of unknown origin to multiple organ dysfunction. Some of these clinical features overlap with presentation of other tropical infections prevalent in Indian subcontinent, which leads to diagnostic dilemma and delay in diagnosis. Hence, we planned this study to know the demographic, clinical and biochemical profile of scrub typhus patients. METHODS: This was an observational study conducted in department of Medicine, King George's Medical University Lucknow, India a leading tertiary care hospital of Northern India. All scrub typhus patients were evaluated by detailed history, examination and laboratory tests. RESULTS: We enrolled 52 patients in our study. The mean age of the patients was 35.17 ± 16.90 years with majority (82.7%) of patients from rural background. All the patients had fever with an average duration of 9.6 ± 2 days. Most of the patients developed hepatitis (69.2%) followed by acute encephalitis syndrome (47%), acute kidney injury (23.1%) and acute respiratory failure (19.2%). Eschar was found in 11 patients (21.2%). CONCLUSION: Scrub typhus is often misdiagnosed or diagnosed late due to its wide clinical spectrum overlapping with clinical presentation of other commonly prevalent tropical diseases. One should always consider the differential diagnosis of scrub typhus while evaluating a young febrile patient of rural background, with features of single or multiple organ dysfunction and laboratory findings of leucocytosis, thrombocytopenia and elevation of transaminases.

SARS-CoV-2 -RNA persists longer in faecal sample as compared to nasal and throat swab samples of COVID-19 patients'; an observational study.

The route of transmission of Novel SARS-CoV-2 virus is ambiguous. In this regard we planned a study to find out SARS-CoV-RNA shedding in various clinical samples of 9 COVID-19 positive patients. SARS-CoV-RNA was detected in nasal swab (NS), throat swab (TS) and faecal sample but was not detected in serum and urine samples. We also report that SARS-CoV-2-RNA persisted in faeces for >20 days. Persistence of faecal RNA might impose challenge in infection control and the disease may spread to household contacts if discharged. Perineal cleaning and hygiene may be advised at the time of vaginal delivery.

Prevalence of thyroid dysfunction in chronic obstructive pulmonary disease patients in a tertiary care center in North India.

INTRODUCTION: Thyroid dysfunction can cause inspiratory and expiratory muscle weakness in patients with or without chronic obstructive pulmonary disease (COPD) Thyroid dysfunction in COPD results in increased frequency of exacerbation thus lead to poor quality of life. It may further increase cardiovascular disease risk thereby increasing mortality. AIMS AND OBJECTIVES: This study was conducted to evaluate the prevalence of thyroid dysfunction and hence that the quality of life of COPD can be improved. MATERIALS AND METHODS: This is a cross-sectional - prevalence study. The study was conducted over a period of 1 year from August 2015 to July 2016. The study group was consists of male and female COPD patients diagnosed with spirometry and severity was determined according to the global initiative for chronic obstructive lung disease classification criteria. The patients were enrolled in this study from medicine outpatient department (OPD), respiratory OPD and those admitted to indoor wards of Medicine Department. Patients were screened for thyroid dysfunction. RESULTS: Out of 171 patients, thyroid dysfunction was present in 43 patients. All of them were hypothyroid. The prevalence of thyroid dysfunction was 25%. In Stage A it was 20.5%, Stage B 25.7%, Stage C 23.4%, and in Stage D 30.4%. Thyroid dysfunction was associated with more frequent exacerbation. CONCLUSION: Thyroid dysfunction is a common extrapulmonary manifestation in COPD patients. It is associated with frequent exacerbations which affect the quality of life in these patients. Early detection and proper management can improve the quality of life in these patients.

A case control study on HDL associated PON1 enzyme level in Northern Indian type 2 diabetes mellitus patients.

AIM: To evaluate the serum paraoxonase 1 activity and determine its association with duration in type 2 Diabetes mellitus patients. METHODS: A total of 80 cases from type 2 diabetes mellitus and healthy controls were enrolled in the present case control study. Human serum PON1 concentration was measured by ELISA and western blotting and it activity was determined spectrophotometrically using 4-nitrophenyle acetate. Diagnostic accuracy of serum PON1 to identify type 2 Diabetes mellitus was calculated with ROC analysis. RESULT: Serum concentration of LDL, VLDL, TG, A1C, FBS and TC levels showed significantly higher levels in type 2 diabetes patients as compared to healthy controls, however there were no significant differences found in the level of HDL. Serum PON1 concentration and activity monitored in patients with >1 year diabetes showed higher level (75.1 ±â€¯6.8 ng/mL) as compared to patients with >3 years diabetes (65.24 ±â€¯1.6 ng/mL), its level was further decreased in patients with >5 (53.8 ±â€¯2.6 ng/mL) and >7 years (48.1 ±â€¯2.7 ng/mL) of diabetes. PON1 concentration decreased as the duration of diabetes increased. PON1 level was further decreased due to habits like smoking and alcohol consumption. CONCLUSION: Serum PON1 levels decrease in states of high oxidative stress like metabolic syndrome, obesity, uncontrolled diabetes, and dyslipidemia. It can be used as diagnostic marker for diabetes mellitus along with increased TG, LDL, VLDL and FBG.

A Study of Cardiovascular Abnormalities in HIV Positive Patients in a Tertiary Care Hospital in Northern India.

Introduction: Cardiovascular illness is common in patients with HIV infection, particularly in the later course of disease. Cardiovascular abnormalities in people living with HIV disease (PLHIV) often go unrecognized or untreated resulting in increased cardiovascular related morbidity and mortality and reduced quality of life. The prevalence of cardiac involvement in PLHIV has been reported to range between 28 to 73%. However, the incidence of symptomatic heart failure in HIV positive patients is 8-10%. Aims and Objectives: The present study had been undertaken to study the prevalence of cardiovascular manifestation in HIV positive patients in north Indian population and its association with HAART, CD4 count and WHO stages of the disease. Material and Methods: This study was conducted in the department of Medicine, KGMU, Lucknow. A total of 75 HIV positive patients of age >15 years, admitted to the hospital were enrolled, out of which 32 were on ART. The cardiovascular evaluation in the form of chest x-ray, ECG, 2D echocardiography and NT-ProBNP was done and their correlations with CD4 count was studied. Two rheumatic heart disease patients were excluded during analysis. Results: Cardiovascular manifestations were found in around 52.1% of HIV positive patients. Chest x-ray showed cardiomegaly in 8 out of 73 patients. ECG abnormalities were found in 49.3% while 2 D echocardiography was abnormal in 52.1% of the patients. Though NT-Pro BNP was abnormal in 26.7% of the patients, no statistical correlation was found with CD4 counts. Conclusion: The prevalence of cardiovascular abnormalities in our study population was 52.1%. Our study did not show any statistical correlation with CD4 counts but showed correlation with the WHO clinical staging of the disease. We suggest a study with larger sample size to see the exact prevalence of cardiovascular disease in HIV positive patients.