Seroprevalence of anti-SARS-CoV-2 IgG antibodies in admitted patients at a tertiary referral centre in North India

BackgroundSeroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate true burden of infection in a given population. Serosurveys, though being conducted in different parts of India, are not readily published in entirety and often do not report on the different characteristics of the population studied. In this present study, we aimed to serially estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody over 11 months at one of the largest government hospital in India. MethodIn this cross-sectional study which was conducted between between 9th June 2020 and 27th April 2021, consecutive patients admitted to medicine wards or intensive care units, who were negative for SARS-CoV-2 by RT-PCR or CBNAAT were included. The 2linic-demographic features of the subjects were recorded in pre-formed questionnaires. Anti-SARS-CoV2 antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method. ResultsA total of 916 patients were recruited over 11 months with mean age({+/-}SD) 39.79{+/-}14.9 of years and 55% of population being males. In total 264(28.8%) patients were found to be seropositive. Residency in Delhi and non-smoking status conferred a higher risk for seropositivity. The adjusted odds ratio for seropositivity with regards to no smoking and residence out of Delhi were .31{+/-}.09 (Odds ratio {+/-} S.E) and .65 {+/-} .1 (Odds ratio {+/-} S.E) respectively. No other factors like age, socio-economic status, contact history etc showed significant relationship with seropositivity. ConclusionThe seropositivity rate among hospitalized patients was found to increase with time (from 8.45% to 38%) over a period of 9 months. Residence in Delhi and non-smokers had higher risk for seropositivity on multivariate analysis.

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

The precise molecular mechanisms behind life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant "classical" signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing "Cytokine Release Syndrome" (CRS) showed upregulation of cytokines such IL1 and CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in "classical" patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.

Impact of COVID-19 on the patients' income and work in Delhi, India.

BACKGROUND: Currently, there is no data on the impact of COVID-19 on patients' income and work in India. METHODS: We conducted a cross-sectional study at a tertiary hospital in New Delhi. We included all the patients who were ≥18 years of age and consecutively diagnosed with COVID-19 between the 1st of May 2020 to 31st July 2020. Patients were interviewed by a physician using a semi-structure questionnaire. Data were collected on socio-economic status, occupation, income loss, leaves taken, decrease in work efficiency (self-perceived) and about-facing any stigma/discrimination at the workplace. RESULTS: Out of 245 patients, 190 patients were employed. A total of 126 patients (66.3%) self-reported their work was affected due to COVID-19 disease. A total of 30.5% of patients (n = 58/190) reported deduction in their salary. The median amount of salary loss was INR 10,000 (IQR 9000-25000). Decrease in income and work efficiency (self-perceived) was found to be 37.3% (n = 71) and 12.1% (n = 23), respectively. A total of 47 patients (37.3%) took personal leaves (median number - 17 days (IQR 14-25), and discrimination/stigma related to the COVID-19 at the workplace was faced by 22.6% of patients. CONCLUSION: Income and work of a substantial number of patients was affected due to COVID-19, as there was a decrease in income and work efficiency. Patients also had to take personal leaves and face stigma in the workplace. This will inform the policymakers to formulate strategies to mitigate the impact of COVID-19.

Determination of utility of 3 minute and 6 minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary hospital in North India

IntroductionThere have been 214 million confirmed cases of COVID-19 worldwide with a total death tally of 4.4 million. The current study aims to determine the predictive value of 3 minute and 6-minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary care hospital in North India. MethodsThe study population consisted of adults (age more than 18 years) with a confirmed diagnosis of Covid-19 by RT-PCR on nasopharyngeal specimens. Patients with only mild illness were enrolled. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, vital signs and laboratory parameters were recorded. The 3 and 6 minute walk test was performed daily from admission till discharge or progression of severity of COVID-19 and it was used to calculate BDS and NEWS2 scores. ResultsOur study consisted of 50 patients with 34 (68%) males and the mean (SD) age of the patient population being 28.1 (6.4) years. The most common symptoms were fever, sore throat, and cough. All laboratory parameters were within normal ranges for all the patients. 96% recovered without progression, while only 4% of them progressed to moderate illness. Results of the 3 and 6 minutes walk tests, BDS and NEWS2 scores showed improvement over the course of hospital stay. ConclusionsAlthough the walk tests and the scores improved over time, they failed to predict the disease progression.

The effectiveness of SARS-CoV-2 vaccination in preventing severe illness and death- real-world data from a cohort of patients hospitalized with COVID-19.

BackgroundDue to the unprecedented speed of SARS-CoV-2 vaccine development, their efficacy trials and issuance of emergency use approvals and marketing authorizations, additional scientific questions remain that need to be answered regarding vaccine effectiveness, vaccination regimens and the need for booster doses. While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited, studies on breakthrough infections help us understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. MethodsThis observational cohort study aimed at comparing the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1,464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. ResultsCompleting the course of vaccination protected individuals from developing severe COVID-19 as evidence by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. ConclusionWith a current rate of only 9.5% of the Indian population being fully vaccinated, efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe Government of India started vaccinating its citizens from the 16th of January 2021, after emergency use authorization had been received for the use of two vaccines, BBV152, a COVID-19 vaccine based on the whole-virion SARS-CoV-2 vaccine strain NIV-2020-770, (Covaxin) and the recombinant replication-deficient chimpanzee adenovirus vector encoding the spike protein ChAdOx1 nCoV-19 Corona Virus Vaccine (Covishield). These have been approved by the Indian regulatory authority based on randomized controlled studies. In these studies, was found that the vaccines led to more than 90% reduction in symptomatic COVID-19 disease. However, there is scarce evidence of the efficacy of these vaccines in real-world scenarios. A few studies have looked at vaccinated cohorts such as health care workers in whom the vaccines had an efficacy similar to the RCTs. In a study of patients with SARS-CoV-2 infection admitted to a tertiary care hospital in New Delhi, it was found that mortality in fully vaccinated patients was 12.5% as compared to 31.5% in the unvaccinated cohort. Added-value of this studyThis cohort of hospitalized patients with SARS-CoV-2 infection was studied during the peak of the second wave of COVID-19 in India during which the delta variant of concern was the predominant infecting strain and had 26% patients who were partially vaccinated and 71.4% who were unvaccinated. Only 3% of the patients were fully vaccinated and developed a breakthrough infection. At the time of presentation, 13% of the individuals with breakthrough infection and 48{middle dot}5% in the non-vaccinated group were hypoxic. Inflammatory markers were significantly lower in the completely vaccinated patients with breakthrough infection. The need for use of steroids and anti-viral agents such as remdesivir was also significantly low in the breakthrough infection group. A significantly less proportion of the individuals with breakthrough infection required oxygen supplementation or ventilatory support. Very few deteriorated or progressed to critical illness during their hospital stay. Only 3 individuals (5.7%) out of the 53 who developed breakthrough infection succumbed to illness while case fatality rates were significantly higher in the unvaccinated (22.8%) and partially vaccinated (19.5%) groups. Propensity score weighted multivariate logistic regression analysis revealed lower odds of developing hypoxia, critical illness or death in those who were completely vaccinated. Implications of all the available evidenceThe real-world effectiveness of the vaccines against SARS-CoV-2 seems to be similar to the randomized controlled trials. The vaccines are very effective in reducing the incidence of severe COVID-19, hypoxia, critical illness and death. The reduced need for oxygen supplementation, mechanical ventilation and the requirement of corticosteroids or other expensive medications such as anti-viral drugs could go a long way in redistributing scarce health care resources. All nations must move forward and vaccinate the citizens, as the current evidence suggests that prevention is better than cure.

Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India-A cohort study

BackgroundThe second wave of the COVID-19 pandemic hit India from early April 2021 to June 2021 and more than 400,000 cases per day were reported in the country. We describe the clinical features, demography, treatment trends, baseline laboratory parameters of a cohort of patients admitted at the All India Institute of Medical Sciences, New Delhi with SARS-CoV-2 infection and their association with the outcome. MethodsThis was a retrospective cohort study describing the clinical, laboratory and treatment patterns of consecutive patients admitted with SARS-CoV-2 infection. Multivariate logistic regression models were fitted to identify the clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay and death. FindingsA total of 2080 patients were included in the study. The case fatality rate was 19.5%. Amongst the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 Acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged 45-60 years [OR (95% CI): 1.8 (1.2-2.6)p =0.003] and those aged >60 years [OR (95%CI): 3.4 (2.3-5.2), p<0.001] had a higher odds of death as compared to the 18-44 age group. Vaccination reduced the odds of death by 30% [OR (95% CI): 0.7 (0.5-0.9), p=0.036]. Patients with hyper inflammation at baseline as suggested by leucocytosis [OR (95% CI): 2.1 (1.4-3.10), p <0.001], raised d-dimer >500 mg/dL [OR (95% CI): 3.2 (2.2-4.6), p <0.001] and raised C-reactive peptide >0.5 mg/L [OR (95% CI): 3.8 (1.1-13), p=0.037] had higher odds of death. Patients who were admitted in the second week had lower odds of death and those admitted in the third week had higher odds of death. InterpretationThis is the largest cohort of patients admitted with COVID-19 from India reported to date and has shown that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Strategies should be made to improve vaccination rates and early admission of patients with moderate and severe COVID-19 to improve outcomes. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic has been ravaging the world since December 2019 and the cases in various regions are being reported in waves. We found that the case fatality rates ranging from 1.4% to 28.3% have been reported in the first wave in India. Older age and the presence of comorbidities are known predictors of mortality. There are no reports regarding the effectiveness of vaccination, correlation of mortality with the timing of admission to the health care facility and inflammatory markers in the second wave of the COVID-19 pandemic in India. Added-value of this studyThis study reports the real-world situation where patients get admitted at varying time points of their illness due to the mismatch between the availability of hospital beds and the rising number of COVID-19 patients during the pandemic. It reports the odds of developing severe hypoxia necessitating oxygen therapy and death thus helping identify priority groups for admission. Implications of all the available evidenceThis study found increased odds of requiring oxygen support or death in patients older than 45 years of age, with comorbidities, and those who had hyper-inflammation with raised C-reactive peptide, d-dimer or leukocytosis. Patients who were admitted in the second week of illness had lower odds of death as compared to those admitted in the third week implying that treatment with corticosteroids in the second week of the illness during the inflammatory phase could lead to reduced mortality. These findings would help triage patients and provide guidance for developing admission policy during times where hospital beds are scarce. Vaccination was found to reduce the odds of deterioration or death and should be fast-tracked to prevent further waves of the pandemic.

Post COVID-19 sequelae: A prospective observational study from Northern India

BackgroundLong COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. AimTo describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. MethodThis prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. ResultsOf 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. ConclusionMost often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.

Novel risk factors for Coronavirus disease-associated mucormycosis (CAM): a case control study during the outbreak in India

BackgroundThe epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. MethodsWe performed a case-control study comparing cases diagnosed with CAM and those who had recovered from COVID-19 without developing mucormycosis (controls). Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Results352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases carried conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95%CI 1.1-11), use of systemic steroids (aOR 7.7,95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6,95% CI 1.2-2.2). Zinc therapy, probably due to its utility in immune function, was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. ConclusionJudicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Use of HFNC in COVID-19 patients in non-ICU setting: Experience from a tertiary referral centre of north India and a systematic review of literature

IntroductionThe rapid surge of cases and insufficient numbers of intensive care unit (ICU) beds have forced hospitals to utilise their general wards for administration of non-invasive respiratory support including HFNC(High Flow Nasal Cannula) in severe COVID-19. However, there is a dearth of data on the success of such advanced levels of care outside the ICU setting. Therefore, we conducted an observational study at our centre, and systematically reviewed the literature, to assess the success of HFNC in managing severe COVID-19 cases outside the ICU. MethodsA retrospective cohort study was conducted in a tertiary referral centre where records of all adult COVID-19 patients ([≥]18 years) requiring HFNC support were between September and December 2020 were analysed. HFNC support was adjusted to target SpO2 [≥]90% and respiratory rate [≤]30 per min. The clinical, demographic, laboratory, and treatment details of these patients were retrieved from the medical records and entered in pre-designed proforma. Outcome parameters included duration of oxygen during hospital stay, duration of HFNC therapy, length of hospital stay and death or discharge. HFNC success was denoted when a patient did not require escalation of therapy to NIV or invasive mechanical ventilation, or shifting to the ICU, and was eventually discharged from the hospital without oxygen therapy; otherwise, the outcome was denoted as HFNC failure. Systematic review was also performed on the available literature on the experience with HFNC in COVID-19 patients outside of ICU settings using the MEDLINE, Web of Science and Embase databases. Statistical analyses were performed with the use of STATA software, version 12, OpenMeta[Analyst], and visualization of the risk of bias plot using robvis. ResultsThirty-one patients receiving HFNC in the ward setting, had a median age of 62 (50 - 69) years including 24 (77%) males. Twenty-one (68%) patients successfully tolerated HFNC and were subsequently discharged from the wards, while 10 (32%) patients had to be shifted to ICU for non-invasive or invasive ventilation, implying HFNC failure. Patients with HFNC failure had higher median D-dimer values at baseline (2.2 mcg/ml vs 0.6 mcg/ml, p=0.001) and lower initial SpO2 on room air at admission (70% vs 80%, p=0.026) as compared to those in whom HFNC was successful .A cut-off value of 1.7 mg/L carried a high specificity (90.5%) and moderate sensitivity (80%) for the occurrence of HFNC failure. Radiographic severity scoring as per the BRIXIA score was comparable in both the groups(11 vs 10.5 out of 18, p=0.78). After screening 98 articles, total of seven studies were included for synthesis in the systematic review with a total of 820 patients, with mean age of the studies ranging from 44 to 83 years and including 62% males. After excluding 2 studies from the analysis, the pooled rates of HFNC failure were 36.3% (95% CI 31.1% - 41.5%) with no significant heterogeneity (I2 =0%, p=0.55). ConclusionsOur study demonstrated successful outcomes with use of HFNC in an outside of ICU setting among two-thirds of patients with severe COVID-19 pneumonia. Lower room air SpO2 and higher D-dimer levels at presentation were associated with failure of HFNC therapy leading to ICU transfer for endotracheal intubation or death. Also, the results from the systematic review demonstrated similar rates of successful outcomes concluding that HFNC is a viable option with failure rates similar to those of ICU settings in such patients.

Seroprevalence of COVID-19 in HIV Population

BackgroundSeroprevalence helps us to estimate the exact prevalence of a disease in a population. Although the world has been battling this pandemic for more than a year now, we still do not know about the burden of this disease in people living with HIV/AIDS (PLHA). Seroprevalence data in this population subset is scarce in most parts of the world, including India. The current study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among PLHA. AimTo determine the seroprevalence of SARS-CoV-2 antibodies in PLHA. MethodThis was a cross-sectional study conducted at a tertiary care hospital in North India. We recruited HIV positive patients following at the ART centre of the institute. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the chemiluminescent immunoassay method. ResultsA total of 164 patients were recruited in the study with a mean age ({+/-}SD) of 41.2 ({+/-}15.4) years, of which 55% were male. Positive serology against SARS CoV-2 was detected in 14% patients (95% CI: 9.1-20.3%). ConclusionThe seroprevalence of COVID-19 infection in PLHA was lower than the general population in the same region, which ranged from 23.48% to 28.3% around the study period.

Clinical correlation of lung ultrasound profiles in patients with COVID-19 infection

BackgroundLung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 patients by determining its ability to predict clinical severity and outcomes. MethodsThis was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 (respiratory rate >30/min OR SpO2<90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 related severity and outcomes. FindingsBetween October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio ({rho}= -0.7232, p<0.0001) and SpO2/FiO2 ratio ({rho}= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of [≥]6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones. InterpretationIn patients with COVID-19, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 infection. Author ApprovalAll authors have seen and approved the manuscript Competing interestsThere are no potential competing interests Data availability StatementAll data referred to in the manuscript shall be provided when asked for. DisclaimersThe authors have nothing to disclose Funding statementNo funding source was involved.

Seroprevalence and attainment of herd immunity against SARS CoV-2: A modelling study

ObjectiveThe present study is aims to predict the likelihood of and likely time required to attain herd immunity against COVID-19 in New Delhi due to natural infection. MethodAn ODE based mathematical model was constructed by extending the classical SEIR model to predict the seroprevalence rate in Delhi. We estimated the parameter values for Delhi using available data (reported cases and the seroprevalence rate) and used them for future prediction. We also attempted to capture the changes in the seroprevalence rate with different possibilities of reinfection. ResultsMaximum seroprevalence rate obtained through our model is 31.65% and also a reduction in the seroprevalence rate was observed for the upcoming one month (month of January, 2021) due to the reduced transmission rate. After increasing the transmission rate to the value same as the third wave in New Delhi, we obtained a maximum value of 54.96%. This maximum value significantly decreased with the reduction in the reinfection possibilities. Also, a little impact of the duration of persistence of antibodies, 180 vs 105 days, was observed on the maximum seroprevalence. ConclusionThis modelling study suggests that natural infection alone, as gauged by serial sero-surveys, will not result in attainment of herd immunity in the state of Delhi.

Low Dose Radiation Therapy for COVID-19 Pneumonia: A Pilot Study

BackgroundThe World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no vaccine or specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. MethodsFrom June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of [≥]5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. ResultsAll patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3-7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. ConclusionResults of our study (90% response rate) suggest the feasibility and clinical effectiveness of LDRT in COVID-19 patients having moderate to severe risk disease. This mandates a randomized controlled trial to establish the clinical efficacy of LDRT in COVID-19 pneumonia.

Clinico-pathological features in fatal Covid-19 Infection: A Preliminary Experience of a Tertiary Care Centre in North India using Post-Mortem Minimally Invasive Tissue Biopsies

BackgroundThe Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than 8.5million cases. Covid-19 infection primarily involves the lung with severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single center study we present the histopathological examination of 37 patients who died with complications of Covid-19. MethodsThis was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken by the help of surface landmarking/ultrasonography guidance from lung, heart, liver, and kidneys; after obtaining ethical consent. The biopsy samples were then stained with haematoxylin and eosin stain. Immunohistochemistry (IHC) was performed using CD61 and CD163 in all lung cores. SARS-CoV-2 virus was detected using IHC with primary antibodies in selected samples. Details regarding demographics, clinical parameters, hospital course, treatment details, and laboratory investigations were also collected for clinical correlation. ResultsA total of 37 patients underwent post-mortem minimally invasive tissue sampling. Mean age of the patients was 48.7years and 59.5% of them were males. Respiratory failure was the most common complication seen in 97.3%. Lung histopathology showed acute lung injury and diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% patients and scattered microthrombi were visualised in 21% patients. Immunostaining with CD61 and CD163 highlighted megakaryocytes, and increased macrophages in all samples. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of the renal biopsies but none of them showed evidence of microvascular thrombosis. 71% of the liver tissue cores showed evidence of Kupfer cell hyperplasia. 27.5% had evidence of submassive hepatic necrosis and 14% had features of acute on chronic liver failure. All the heart biopsies showed non-specific features such as hypertrophy with nucleomegaly with no evidence of myocardial necrosis in any of the samples. ConclusionsThe most common finding in this cohort is the diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase of DAD. Microvascular thrombi were rarely identified in the lung, liver and kidney. Substantial hepatocyte necrosis, hepatocyte degeneration, Kupffer cell hypertrophy, micro, and macrovesicular steatosis unrelated to microvascular thrombi suggests that liver might be a primary target of Covid-19. This study highlights the importance of MITS/B in better understanding the pathological changes associated with Covid-19.

Seroprevalence of anti-SARS-CoV-2 IgG antibody in hospitalized patients in a tertiary referral center in North India

BackgroundSeroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India. MethodThis cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method. ResultsA total of 212 hospitalized patients were recruited in the study with mean age ({+/-}SD) of 41.2 ({+/-}15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8% patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity. ConclusionAround, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)

Risk stratification as a tool to rationalize quarantine among health care workers exposed to COVID-19 cases - Evidence from a tertiary healthcare centre in India

BackgroundQuarantine of healthcare workers (HCWs) exposed to COVID -19 confirmed cases is a well-known strategy for limiting the transmission of infection. However, there is need of evidence-based guidelines for quarantine of HCWs in COVID -19. MethodsWe describe our experience of contact tracing and risk stratification of 3853 HCWs who were exposed to confirmed COVID-19 cases in a tertiary health care institution in India. We developed an algorithm, on the basis of risk stratification, to rationalize quarantine among HCWs. Risk stratification was based on the duration of exposure, distance from the patient, and appropriateness of personal protection equipment (PPE) usage. Only high-risk contacts were quarantined for 14 days. They underwent testing for COVID-19 after five days of exposure, while low-risk contacts continued their work with adherence to physical distancing, hand hygiene, and appropriate use of PPE. The low-risk contacts were encouraged to monitor for symptoms and report for COVID-19 screening if fever, cough, or shortness of breath occurred. We followed up all contacts for 14 days from the last exposure and observed for symptoms of COVID-19 and test positivity. Results and interpretationOut of total 3853 contacts, 560 (14.5%) were categorized as high-risk contacts, and 40 of them were detected positive for COVID-19, with a test positivity rate of 7.1% (95% CI = 5.2 - 9.6). Overall, 118 (3.1%) of all contacts tested positive. Our strategy prevented 3215 HCWs from being quarantined and saved 45,010 person-days of health workforce until June 8, 2020, in the institution. We conclude that exposure-based risk stratification and quarantine of HCWs is a viable strategy to prevent unnecessary quarantine, in a healthcare institution. SummaryO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIQuarantine of HCWs is a well-known strategy for community and HCWs to prevent the transmission of COVID-19. C_LIO_LIThough success stories of prompt contact tracing and quarantine to control COVID-19 are available from countries like South Korea, Singapore, and Hong Kong, there is a scarcity of evidence that could guide targeted quarantine of HCWs exposed to COVID -19 in India. C_LI What does this study add?O_LIOnly 14.5% HCWs exposed to COVID-19 cases were stratified "high risk" contacts, and the most common reason for high-risk contacts was non-formal workplace interactions such as having meals together. C_LIO_LIThe overall test positivity rate among the high-risk contacts was 7.1%, while it was higher in symptomatic high-risk contacts as compared to those who were asymptomatic (10.2% vs. 6.3%). C_LI How might this impact on clinical practice?O_LIContact tracing and risk stratification can be used to minimize unnecessary quarantine of COVID-19 exposed health care workers and prevent the depletion of healthcare workers amidst the pandemic to continue the healthcare services optimally. C_LI

SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients : a retrospective observational study

BackgroundDespite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve. AimTo analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients. DesignIt was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi. MethodsPatients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records. Results298 patients were included, majority were males (75{middle dot}8%) with mean age of 39{middle dot}07 years (0{middle dot}6-88 years). The mean duration from symptom onset to first positive RT-PCR was 4{middle dot}7 days (SD 3{middle dot}67), while that of symptom onset to last positive test was 17{middle dot}83 days (SD 6{middle dot}22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8{middle dot}7% and 20{middle dot}6% in the 1st, 2nd, 3rd, 4th & >4 weeks of illness. 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age >= 60 years was associated with prolonged RT-PCR positivity (statistically significant). ConclusionThis study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.

Management of mild COVID-19: Policy implications of initial experience in India

ObjectivesOngoing pandemic due to COVID-19 has spread across countries, surprisingly with variable clinical characteristics and outcomes. This study was aimed at describing clinical characteristics and outcomes of admitted patients with mild COVID-19 illness in the initial phase of pandemic in India. DesignRetrospective (observational) study. SettingCOVID facilities under AIIMS, New Delhi, where, isolation facilities were designed to manage patients with mild illness and dedicated COVID ICUs was created to cater patients with moderate to severe illness. ParticipantsPatients aged 18 years or more, with confirmed illness were eligible for enrolment. Patients who were either asymptomatic or mildly ill at presentation were included. Patients with moderate to severe illness at admission, or incomplete clinical symptomatology records were excluded. MethodsData regarding demographic profile, comorbidities, clinical features, hospital course, treatment, details of results of RT-PCR for SARS-CoV-2 done at baseline and at day 14, chest radiographs (wherever available) as well as laboratory parameters was obtained retrospectively from the hospital records. Main outcome measuresFinal outcome was noted in terms of course of the disease, patients discharged, still admitted (at time of conclusion of study) or death. ResultsOut of 231 cases included, majority were males(78{middle dot}3%) with a mean age of 39{middle dot}8 years. Comorbidities were present in 21{middle dot}2% of patients, diabetes mellitus and hypertension being most common. The most common symptoms were dry cough(81, 35%), fever(64, 27{middle dot}7%), sore throat(36, 15{middle dot}6%), and dyspnoea(24, 10{middle dot}4%); asymptomatic infection was noted in 108(46.8%) patients. Presence of comorbidities was an independent predictor of symptomatic disease (OR- 2{middle dot}66; 95% CI 1{middle dot}08 to 6{middle dot}53, p= 0{middle dot}03). None of the patients progressed to moderate to severe COVID-19. There were no deaths in this cohort. ConclusionsPatients with mild disease at presentation had a stable disease course and therefore such cases can be managed outside hospital setting. A large proportion of patients remained asymptomatic throughout the course of infection and those with comorbidities are more likely to be symptomatic. Trial registrationNot applicable

Diagnostic Evaluation of Non-Interpretable Results Associated with rpoB Gene in Genotype MTBDRplus Ver 2.0 / 결핵및호흡기질환

Background@#Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Noninterpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. @*Methods@#Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culturepositive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. @*Results@#A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). @*Conclusion@#The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

Assessment of core capacities for antimicrobial stewardship practices in indian hospitals: Report from a multicentric initiative of global health security agenda.

Introduction: Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP. We conducted an assessment of the core capacities for AMSP in a network of Indian hospitals, which are part of the Global Health Security Agenda-funded work on capacity building for AMR-HAIs. Subjects and Methods: The Centers for Disease Control and Prevention's core assessment checklist was modified as per inputs received from the Indian network. The assessment tool was filled by twenty hospitals as a self-administered questionnaire. The results were entered into a database. The cumulative score for each question was generated as average percentage. The scores generated by the database were then used for analysis. Results and Conclusion: The hospitals included a mix of public and private sector hospitals. The network average of positive responses for leadership support was 45%, for accountability; the score was 53% and for key support for AMSP, 58%. Policies to support optimal antibiotic use were present in 59% of respondents, policies for procurement were present in 79% and broad interventions to improve antibiotic use were scored as 33%. A score of 52% was generated for prescription-specific interventions to improve antibiotic use. Written policies for antibiotic use for hospitalised patients and outpatients were present on an average in 72% and 48% conditions, respectively. Presence of process measures and outcome measures was scored at 40% and 49%, respectively, and feedback and education got a score of 53% and 40%, respectively. Thus, Indian hospitals can start with low-hanging fruits such as developing prescription policies, restricting the usage of high antibiotics, enforcing education and ultimately providing the much-needed leadership support.