Breakthrough SARS-CoV-2 infections among BBV-152 (COVAXIN®) and AZD1222 (COVISHIELDTM ) recipients: Report from the eastern state of India.

In this study, we attempted to record the breakthrough cases reported through passive and voluntary reporting at various healthcare facilities from different districts of Odisha, their clinical presentation, requirement of hospitalization postinfection, and antibody titer against spike antigen. Nasopharyngeal swab and serum samples alongwith demographic, clinical presentation and requirement of hospitalization postinfection were collected from vaccinated individuals through passive and voluntary reporting to various healthcare facilities of Odisha state to detect the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection and quantitative estimation of antibody titers. A total of 274 samples were found to be positive after 14 days of receiving complete doses of the vaccines. More than 83.2% of the individuals were found to be symptomatic with 9.9% of those required hospitalization. The seropositivity in individuals receiving Covishield (96.7%) was significantly higher than in Covaxin (77.1%). Hospitalized patients were having less median antibody titers than individuals in home isolation. The median age for breakthrough infection among the referred cases was 47.0 years (interquartile range [IQR]: 28.0) with a significantly older age group among Covishield recipients. The median spike receptor binding domain IgG titer values for Covaxin and Covishield recipients were 213.5 AU/ml (IQR: 537.5) and 647.5 AU/ml (IQR: 1645.1), respectively. The results reported here highlight the need for systematic data capture for the breakthrough infections to monitor the emergence of any vaccine escape variants and to plan the next steps in the coronavirus disease-19 (COVID-19) vaccine development by understanding the link between clinical protection and measured immunity against SARS-CoV-2 infection.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Saliva for diagnosis of SARS-CoV-2: First report from India.

There are very few studies in search of an alternate and convenient diagnostic tool which can substitute nasopharyngeal swab (NPS) specimen for detection of SARS-CoV-2. In the study we analyzed, the comparison and agreement between the feasibility of using the saliva in comparison to NPS for diagnosis of SARS-CoV-2. A total number of 74 patients were enrolled for this study. We analyzed and compared the NPS and saliva specimen collected within 48 h after the symptom onset. We carried out real-time quantitative polymerase chain reaction, gene sequencing for the detection and determination SARS-CoV-2 specific genes. Phylogenetic tree was constructed to establish the isolation of viral RNA from saliva. We used the Bland-Altman model to identify the agreement between two specimens. This study showed a lower cycle threshold (CT ) mean value for the detection of SARS-CoV-2 ORF1 gene (mean, 27.07; 95% confidence interval [CI], 25.62 to 28.52) in saliva methods than that of NPS (mean 28.24; 95% CI, 26.62 to 29.85) specimen although the difference is statistically nonsignificant (p > .05). Bland-Altman analysis produced relatively smaller bias and high agreement between these two clinical specimens. Phylogenetic analysis with the RdRp and S gene confirmed the presence of SARS-CoV-2 in the saliva samples. Saliva represented a promising tool in COVID-19 diagnosis and the collection method would reduce the exposure risk of frontline health workers which is one of the major concerns in primary healthcare settings.

IgG antibody response against nucleocapsid and spike protein post-SARS-CoV-2 infection.

OBJECTIVES: Coronavirus disease-19 (COVID-19) pandemic became the greatest public health challenge globally. Study of dynamicity and durability of naturally developed antibodies against SARS-CoV-2 are of great importance from an epidemiological viewpoint. METHODS: In this observational cohort study, we have followed up the 76 individuals who tested positive for SARS-CoV-2 infection by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) for 16 weeks (post-enrolment) to record the periodic changes in titre, concentration, clinical growth and persistence of naturally developed SARS-CoV-2 antibodies. We collected serum samples from these individuals for 16 weeks with a frequency of weekly and fortnightly during each follow-up and tested them in two CLIA-based platforms (Abbott Architect i1000SR and Roche Cobas e411) for testing SARS-CoV-2 antibodies both qualitatively and quantitatively. RESULTS: We recorded the antibody magnitude of these individuals 10 times between September 2020 and February 2021. We found a waning of antibodies against nucleocapsid antigen protein but not a complete disappearance by the end of 16 weeks. Out of 76 cases, 30 cases (39.47%) became seronegative in qualitative assay, although all the sera samples (100%) remained positive when tested in quantitative assay. CONCLUSION: The lower persistence of anti-nucleocapsid SARS-CoV-2 antibody may not be the exact phenomenon as those cases were still seropositive against spike protein and help in neutralising the virus.

Pooled testing for SARS-CoV-2 infection in an automated high-throughput platform.

BACKGROUND: Active detection of SARS-CoV-2 infection through testing is elementary for the control of COVID-19 pandemic. The implementation of large-scale RT-PCR testing has led to a rise in the demand for testing kits whose availability is always a concern. OBJECTIVE: To find out the feasibility of pooled testing in a high-throughput platform. METHODOLOGY: Pooled testing was conducted in Roche cobas 6800 in 2 methods. Firstly, the simple two-stage testing algorithm was conducted for 1410 samples individually and then as pooled samples. Secondly, we evaluated the sensitivity of cobas 6800 for the detection of a single positive sample within a pool of negative samples. RESULTS: Implementing the five-sample Dorfman pooling to test 1410 samples, we identified 42 (2.9%) individual SARS-CoV-2-positive samples and 27 (9.5%) positive pool samples. The pooling strategy precisely identified all the positive samples. All individually negative samples were also accurately determined by pooling. There was 100% sensitivity of detecting positive samples in a pool of negative samples even up to 1:64 dilution. There was a threefold increase in total throughput in one-third of the cost per day. CONCLUSION: A high-throughput platform such as Cobas 6800 can effectively increase the testing capacity by twofold to threefold by adopting the pooled testing strategy for successful management of SARS-CoV-2 and helping in the containment of community transmission.

Scrub typhus seroprevalence from an eastern state of India: findings from the state-wide serosurvey.

BACKGROUND: Scrub typhus is a mite-borne infectious disease caused primarily by the obligate intracellular bacteria Orientia tsutsugamushi, which is transmitted by chigger mites. The objective of this study was to determine the prevalence of scrub typhus among adults in Odisha, an eastern state of India. METHODS: A descriptive cross-sectional study was conducted to analyse 1840 serum samples from five districts (Khordha, Cuttack, Ganjam, Malkangiri and Sundargarh) of Odisha collected during 2020-2021. Both immunoglobulin G (IgG) and IgM antibodies against scrub typhus were tested using commercial enzyme-linked immunosorbent assay kits. Point estimates of the 95% confidence interval and adjusted odds ratio were calculated. RESULTS: Of 1840 participants, the prevalence of IgG positivity was 1034 (56.19%) and that of IgM was 523 (28.42%). The majority of participants were in the 18-45 y age group (53.7%). Cuttack had the highest IgG positivity (64.54%) and Malkangiri had the lowest (29.32%). The highest and lowest positivity for IgM were found in Malkangiri (40.84%) and Cuttack (25.30%), respectively. CONCLUSIONS: With an increasing number of infections detected in the state, scrub typhus is emerging as a public health threat. Increasing awareness among the general public and healthcare professionals through health education campaigns regarding scrub typhus is essential. Early detection of the disease through the establishment of a laboratory surveillance system is required to control the transmission of scrub typhus.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Evidence for intensive LDL-C lowering for acute coronary syndrome: Recommendations from the Lipid Association of India.

Patients with acute coronary syndrome (ACS) have a high risk of subsequent adverse cardiovascular outcomes, particularly within the first 30 days. Although it is well documented that initiation of statin therapy in the setting of ACS improves short- and long-term cardiovascular outcomes, and achievement of lower levels of low density lipoprotein cholesterol (LDL-C) incrementally improves outcomes, many patients with ACS have persistent hypercholesterolemia after discharge from the hospital. This is a missed opportunity that prompted the Lipid Association of India to develop recommendations for earlier initiation of more aggressive LDL-C lowering treatment, particularly for patients of South Asian descent who are well-documented to have earlier onset of more aggressive atherosclerotic cardiovascular disease. The Lipid Association of India recommends individualized aggressive LDL-C goals after ACS, which can be rapidly achieved with high intensity statin therapy and subsequent goal-directed adjunctive treatment with ezetimibe and PCSK9 inhibitors. Improved treatment of hypercholesterolemia achieved within weeks after ACS has the potential to reduce the high rate of morbidity and mortality in these high risk patients.

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Diagnostic accuracy comparison of three fully automated chemiluminescent immunoassay platforms for the detection of SARS-CoV-2 antibodies.

BACKGROUND: Serological test is an essential surveillance tool to track down the extensiveness of SARS-CoV-2 transmission and subsequently to move out from the enforced lockdown stage. OBJECTIVE: The study measures the diagnostic accuracy of three popular chemiluminescent immunoassay (CLIA) based automated platforms for the detection of anti-SARS-CoV-2 antibodies and compares their agreements. STUDY DESIGN: Serum samples of 594 COVID-19 positive patients and 100 samples from pre-COVID cases were tested by three CLIA based automated platforms: Abbott architect i2000SR, Roche cobas e411 and Yhlo iFlash 1800 and their diagnostic accuracy were compared by the area under the curves (AUC) value obtained from receiver operator characteristic (ROC) curves. Cohen's kappa statistic and McNemar's test were used to interpret the agreement between the platforms. RESULTS: All three platforms showed high specificity as claimed by the manufacturer. Sensitivity was calculated as 64.48 % (58.67-70.3) for Abbott, 80.48 % (76.62-84.34) for Roche and 76.94 % (72.65-81.23) for Yhlo. AUC was maximum for Roche (0.929). The Cohen's kappa value was determined in between 0.69-0.89 as the inter-rater agreements. CONCLUSION: The overall statistical analysis demonstrated cobas e411 as the diagnostically most accurate platform among the three.

SARS-CoV-2 IgG antibody responses in rt-PCR-positive cases: first report from India.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. AIM: To understand the relationship between the antibody response to SARS-CoV-2 infection and the demographics and cycle threshold (C t) values of confirmed RT-PCR patients. METHODOLOGY: A total of 384 serum samples were collected from individuals between 4-6 weeks after confirmed SARS-CoV-2 infection and tested for the development of immunoglobulin class G (IgG) against SARS-CoV-2. The C t values, age, gender and symptoms of the patients were correlated with the development of antibodies. RESULTS: IgG positivity was found to be 80.2 % (95 % CI, 76.2-84.2). Positivity increased with a decrease in the C t value, with the highest (87.6 %) positivity observed in individuals with C t values <20. The mean (±sd) C t values for IgG positives and negatives were 23.34 (±6.09) and 26.72 (±7.031), respectively. No significant difference was found for demographic characteristics such as age and sex and symptoms and antibody response. The current study is the first of its kind wherein we have assessed the correlation of the RT-PCR C t with the development of IgG against SARS-CoV-2. CONCLUSION: Although C t values might not have any relation with the development of symptoms, they are associated with the antibody response among SARS-CoV-2-infected individuals.

COVID-19 in children in Odisha state, India: a retrospective review.

We retrospectively analysed the swab samples tested for COVID-19 from 7 March 2020 to 17 August 2021 at the Indian Council of Medical Research-Regional Medical Research Centre, Bhubaneswar, Odisha. 553 763 nasopharyngeal swabs were collected from individuals suspected with COVID-19 in Odisha state. 75 190 (13.6%) samples were positive by reverse transcription-PCR. There were 5988 (8%) cases in children and young people under 18 years old. Odisha reported 996 153 COVID-19 cases which resulted in 6985 deaths in adults and 36 in children and young people under 18 years old.