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   Table of Contents - Current issue
Coverpage
January & February 2021
Volume 153 | Issue 1 & 2
Page Nos. 1-240

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EDITORIAL  

The quest continues for perfect COVID-19 vaccine Highly accessed article p. 1
Rajesh Bhatia
DOI:10.4103/ijmr.IJMR_4165_20  PMID:33361644
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REVIEW ARTICLES Top

Cardiovascular manifestations of COVID-19: An evidence-based narrative review p. 7
Yash Paul Sharma, Sourabh Agstam, Ashutosh Yadav, Anunay Gupta, Ankur Gupta
DOI:10.4103/ijmr.IJMR_2450_20  PMID:33281125
The recent outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization on March 11, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily involves the respiratory system with viral pneumonia as a predominant manifestation. In addition, SARS-CoV-2 has various cardiovascular manifestations which increase morbidity and mortality in COVID-19. Patients with underlying cardiovascular diseases and conventional cardiovascular risk factors are predisposed for COVID-19 with worse prognosis. The possible mechanisms of cardiovascular injury are endothelial dysfunction, diffuse microangiopathy with thrombosis and increased angiotensin II levels. Hyperinflammation in the myocardium can result in acute coronary syndrome, myocarditis, heart failure, cardiac arrhythmias and sudden death. The high level of cardiac troponins and natriuretic peptides in the early course of COVID-19 reflects an acute myocardial injury. The complex association between COVID-19 and cardiovascular manifestations requires an in-depth understanding for appropriate management of these patients. Till the time a specific antiviral drug is available for COVID-19, treatment remains symptomatic. This review provides information on the cardiovascular risk factors and cardiovascular manifestations of COVID-19.
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An overview of preclinical animal models for SARS-CoV-2 pathogenicity p. 17
Itti Munshi, Aditya Khandvilkar, Shrinivas M Chavan, Geetanjali Sachdeva, Smita D Mahale, Uddhav K Chaudhari
DOI:10.4103/ijmr.IJMR_3215_20  
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of fatalities globally since its origin in November 2019. The SARS-CoV-2 shares 79 and 50 per cent genome similarity with its predecessors, severe SARS-CoV and Middle East respiratory syndrome (MERS) coronavirus, all belonging to the same genus, Betacoronavirus. This relatively new virus has stymied the effective control of COVID-19 pandemic and caused huge social and economic impact worldwide. The FDA-approved drugs were re-purposed to reduce the number of fatalities caused by SARS-CoV-2. However, controversy surrounds about the efficacy of these re-purposed antiviral drugs against SARS-CoV-2.This necessitates the identification of new drug targets for SARS-CoV-2. Hence, the development of pre-clinical animal model is warranted. Such animal models may help us gain better understanding of the pathophysiology of SARS-CoV-2 infection and will be effective tools for the evaluation and licensure of therapeutic strategies against SARS-CoV-2. This review provides a summary of the attempts made till to develop a suitable animal model to understand pathophysiology and effectiveness of therapeutic agents against SARS-CoV-2.
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Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India p. 26
M Vishnu Vardhana Rao, Atul Juneja, Mohua Maulik, Tulsi Adhikari, Saurabh Sharma, Jyotsna Gupta, Yashmin Panchal, Neha Yadav
DOI:10.4103/ijmr.IJMR_2556_20  PMID:33146154
Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.
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Use of convalescent plasma for COVID-19 in India: A review & practical guidelines p. 64
Niranjan Shiwaji Khaire, Nishant Jindal, Lakshmi Narayana Yaddanapudi, Suchet Sachdev, Rekha Hans, Naresh Sachdeva, Mini P Singh, Anup Agarwal, Aparna Mukherjee, Gunjan Kumar, Ratti Ram Sharma, Vikas Suri, Goverdhan Dutt Puri, Pankaj Malhotra
DOI:10.4103/ijmr.IJMR_3092_20  PMID:33533733
Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.
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Computed tomography chest in COVID-19: When & why? p. 86
Mandeep Garg, Nidhi Prabhakar, Ashu Seith Bhalla, Aparna Irodi, Inderpaul Sehgal, Uma Debi, Vikas Suri, Ritesh Agarwal, Laxmi Narayana Yaddanapudi, Govardhan Dutt Puri, Manavjit Singh Sandhu
DOI:10.4103/ijmr.IJMR_3669_20  PMID:33402610
Computed tomography (CT) of the chest plays an important role in the diagnosis and management of coronavirus disease 2019 (COVID-19), but it should not be used indiscriminately. This review provides indications of CT chest in COVID-19 suspect, positive and recovered patients based on the current scientific evidence and our personal experience. CT chest is not indicated as a routine screening modality due to its poor sensitivity and specificity. However, it is useful in a small subset of COVID-19 suspects who test negative on reverse transcription-polymerase chain reaction (RT-PCR) with normal/indeterminate chest X-ray (CXR) but have moderate-to-severe respiratory symptoms and high index of clinical suspicion. CT chest is not indicated in every RT-PCR–positive patient and should be done only in specific clinical scenarios, where it is expected to significantly contribute in the clinical management such as COVID-19 patients showing unexplained clinical deterioration and/or where other concurrent lung pathology or pulmonary thromboembolism needs exclusion. Serial CXR and point-of-care ultrasound are usually sufficient to evaluate the progression of COVID-19 pneumonia. CT chest is also indicated in COVID-19–positive patients with associated co-morbidities (age >65 yr, diabetes, hypertension, obesity, cardiovascular disease, chronic respiratory disease, immune-compromise, etc.) who, despite having mild symptoms and normal/indeterminate CXR, record oxygen saturation of <93 per cent at rest while breathing room air or de-saturate on six-minute walk test. Finally, CT chest plays a crucial role to rule out lung fibrosis in patients recovered from COVID-19 infection who present with hypoxia/impaired lung function on follow up. In conclusion, though CT chest is an indispensable diagnostic tool in COVID-19, it should be used judiciously and only when specifically indicated.
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SYSTEMATIC REVIEW Top

Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates Highly accessed article p. 93
Labanya Mukhopadhyay, Pragya D Yadav, Nivedita Gupta, Sreelekshmy Mohandas, Deepak Y Patil, Anita Shete-Aich, Samiran Panda, Balram Bhargava
DOI:10.4103/ijmr.IJMR_4431_20  PMID:33361645
Background & objectives: The COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission, with a few vaccines having progressed to advanced stages of clinical trials. The aim of this systematic review was to compare immunogenicity and protective efficacy of various SARS-CoV-2 vaccine candidates tested in non-human primate (NHP) models. Methods: Literature on effect of SARS-CoV-2 vaccines in NHP models reported on PubMed and preprint platforms (medRxiv and bioRxiv) till October 22, 2020, was searched with the following terms: coronavirus vaccine, COVID-19 vaccine, SARS-CoV-2 vaccine, nonhuman primate, and rhesus macaque. Results: Our search yielded 19 studies, which reported immune response elicited by 18 vaccine candidates in NHP. All the vaccines induced detectable neutralizing antibody (NAb) titres in the serum of vaccinated animals, with some showing effective viral clearance from various organs. The vaccinated animals also showed nil to mild histopathological changes in their lungs compared to placebo groups in the trials that performed necropsy. Interpretation & conclusions: Our findings highlighted onset of quick immunogenicity and protective efficacy of mRNA-1273, followed by Ad26.CoV2.S, NVX-CoV2373, BNT162b2, RBD and BBV152 vaccine candidates in preclinical trials as compared to the others. NHP data also showed correlation with clinical trial data available for a few vaccines. Preclinical trials of COVID-19 vaccine candidates in NHPs yielded promising results, with some candidates faring better than others.
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ORIGINAL ARTICLES Top

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India p. 115
Shiv Lal Soni, Kamal Kajal, LN Yaddanapudi, Pankaj Malhotra, Goverdhan Dutt Puri, Ashish Bhalla, Mini P Singh, Inderpaul Singh Sehgal, Vipin Koushal, Neelam Varma, Manisha Biswal, P.V.M. Lakshmi, Sadhna Sharma, Vikas Suri, Z Deepy, Sant Ram, Jaivinder Yadav, Navin Pandey, Prashant Sharma, Nabhajit Malik, Kapil Goyal, Aseem Mehra, Swapnajeet Sahoo, Ritin Mohindra, Jijo Francis, Mudit Bhargava, Karan Singla, Preena Babu, Amiy Verma, Niranjan Shiwaji Khaire, RR Guru
DOI:10.4103/ijmr.IJMR_2311_20  PMID:33208558
Background & objectives: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India. Methods: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines. Results: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO2<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed. Interpretation & conclusions: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.
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Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India p. 126
Ankesh Gupta, Surbhi Khurana, Rojaleen Das, Deepankar Srigyan, Amit Singh, Ankit Mittal, Parul Singh, Manish Soneja, Arvind Kumar, Akhil Kant Singh, Kapil Dev Soni, Suneeta Meena, Richa Aggarwal, Neha Sharad, Anivita Aggarwal, Harshith Kadnur, Netto George, Komal Singh, Devashish Desai, Praveen Trilangi, Adil Rashid Khan, Vandana V Kiro, Shivdas Naik, Bharthi Arunan, Shivam Goel, Diksha Patidar, Amit Lathwal, Lalit Dar, Anjan Trikha, Ravindra Mohan Pandey, Rajesh Malhotra, Randeep Guleria, Purva Mathur, Naveet Wig
DOI:10.4103/ijmr.IJMR_3305_20  PMID:33146157
Background & objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR). Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests. Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days. Interpretation & conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.
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Drug repurposing for identification of potential inhibitors against SARS-CoV-2 spike receptor-binding domain: An in silico approach p. 132
Santosh Kumar Behera, Namita Mahapatra, Chandra Sekhar Tripathy, Sanghamitra Pati
DOI:10.4103/ijmr.IJMR_1132_20  PMID:33281124
Background & objectives: The world is currently under the threat of coronavirus disease 2019 (COVID-19) infection, caused by SARS-CoV-2. The objective of the present investigation was to repurpose the drugs with potential antiviral activity against receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein among 56 commercially available drugs. Therefore, an integrative computational approach, using molecular docking, quantum chemical calculation and molecular dynamics, was performed to unzip the effective drug-target interactions between RBD and 56 commercially available drugs. Methods: The present in silico approach was based on information of drugs and experimentally derived crystal structure of RBD of SARS-CoV-2 S protein. Molecular docking analysis was performed for RBD against all 56 reported drugs using AutoDock 4.2 tool to screen the drugs with better potential antiviral activity which were further analysed by other computational tools for repurposing potential drug or drugs for COVID-19 therapeutics. Results: Drugs such as chalcone, grazoprevir, enzaplatovir, dolutegravir, daclatasvir, tideglusib, presatovir, remdesivir and simeprevir were predicted to be potentially effective antiviral drugs against RBD and could have good COVID-19 therapeutic efficacy. Simeprevir displayed the highest binding affinity and reactivity against RBD with the values of −8.52 kcal/mol (binding energy) and 9.254 kcal/mol (band energy gap) among all the 56 drugs under investigation. Interpretation & conclusions: In the current investigation, simeprevir was identified as the potential antiviral drug based on the in silico findings in comparison to remdesivir, favipiravir and other 53 drugs. Further, laboratory and clinical investigations are needed to be carried out which will aid in the development of quick therapeutics designed for COVID-19.
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Performance evaluation of Truenat™ Beta CoV & Truenat™ SARS-CoV-2 point-of-care assays for coronavirus disease 2019 p. 144
Shantala Gowdara Basawarajappa, Ambica Rangaiah, Shashiraja Padukone, Pragya D Yadav, Nivedita Gupta, Sathyanarayan Muthur Shankar
DOI:DOI: 10.4103/ijmr.IJMR_2363_20  PMID:33146156
Background & objectives: The rapid diagnosis of coronavirus disease 2019 (COVID-19) is a significant step towards the containment of the virus. The surge of COVID-19 cases in India and across the globe necessitates a rapid and sensitive molecular assay. Rapid point-of-care (PoC) assays (Truenat Beta CoV and Truenat SARS-CoV-2 assays) for the diagnosis of COVID-19 have been developed which are expected to shorten the turnaround time of reporting of results and also can be used for field investigations of COVID-19. The objectives of the study were to validate the performance of Truenat Beta CoV and Truenat SARS-CoV-2 PoC assays for the detection of SARS-CoV-2 infected cases with reference to analytical sensitivity, precision/inter-machine variation, clinical sensitivity and clinical specificity. Methods: The rapid PoC screening and confirmatory assays were prospectively validated at the State Level Virus Research and Diagnostic Laboratory at Bangalore Medical College and Research Institute, Bengaluru, under technical supervision by the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune. Real-time reverse transcription-polymerase chain reaction (rRT-PCR)was considered as the reference standard against which the rapid assays were validated for all samples tested based on analytical sensitivity, precision/inter-machine variation, clinical sensitivity and clinical specificity. Results: Truenat Beta CoV and Truenat SARS-CoV-2 assays showed concordant results when compared with the reference standard rRT-PCR. These PoC assays exhibited 100 per cent sensitivity, specificity, positive predictive value and negative predictive value. Interpretation & conclusions: Truenat Beta CoV and Truenat SARS-CoV-2 assays showed concordance with the reference standard assay and may be recommended for screening and confirmation of SARS-CoV-2 in the field settings.
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Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial p. 151
Alok Thakar, Smriti Panda, Pirabu Sakthivel, Megha Brijwal, Shivram Dhakad, Avinash Choudekar, Anupam Kanodia, Sushma Bhatnagar, Anant Mohan, Subir K Maulik, Lalit Dar
DOI:10.4103/ijmr.IJMR_3665_20  PMID:33473017
Background & objectives: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing viral load and preventing clinical progression in early COVID-19 infection. Methods: This randomized clinical trial was done with a sample size of 60. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed asymptomatic patients or those with mild COVID-19 illness [National Early Warning Score (NEWS) ≤4] were included. Patients were randomized in a 1:1 manner. Control arm (standard supportive treatment, n=30) was compared with intervention arm (n=30) of standard treatment plus CQN eye drops (0.03%) repurposed as nasal drops administered six times daily (0.5 ml/dose) for 10 days. Outcome measures were adverse events and adherence; clinical progression and outcomes were measured by NEWS; sequential RT-PCR cycle threshold (Ct) values were also noted on days 0, 3, 7 and 10. Results: Nasal CQN was associated with local irritation in seven and non-compliance in one of 30 patients. Eleven patients were excluded due to enrolment error (2 – recovered; 9 – false-positive referral), and 49 patients were analyzed as per modified intention-to-treat analysis. Clinical recovery was noted as similar with 100 per cent asymptomatic by day seven in both arms. Virological outcomes also indicated similarly improving Ct values in both arms, and similar proportion of patients transitioning to non-infectivity by day 10 (controls - 19/25; nasal CQN - 15/24). Nine false-positive patients with enrolment error and day 0 RT-PCR negative were initially uninfected but had continuing COVID-19 exposure and treatment as per randomization. Patients receiving nasal CQN (n=5) demonstrated stable Ct values from day 0 to 10, while patients with no nasal CQN (n=4) demonstrated significant dip in Ct value indicating to infection (Ct<35) and infectivity (Ct<33). Interpretation & conclusions: The present study suggests to the potential of topical nasal CQN in the prevention of COVID-19 infection if administered before the infection is established. No significant differences in clinical or virological outcome were however, demonstrated in patients with mild but established illness.
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SARS-CoV-2 detection in sewage samples: Standardization of method & preliminary observations p. 159
Deepa Kailash Sharma, Uma Prajwal Nalavade, Kamlesh Kalgutkar, Nivedita Gupta, Jagadish Mohanrao Deshpande
DOI:10.4103/ijmr.IJMR_3541_20  PMID:33318343
Background & objectives: Since its first recognition in Wuhan, China, in December 2019, the SARS-CoV-2 has spread rapidly across the world. Though SARS-CoV-2 spreads mainly via the droplets of respiratory secretions, it was also detected in stool samples of patients, indicating active infection of the gastrointestinal tract. Presence of SARS-CoV-2 RNA in sewage samples was reported in February 2020, raising the possibility of using environmental water surveillance to monitor SARS-CoV-2 activity in infected areas. The aim of this study was to standardize the methodology for detection of SARS-CoV-2 from sewage and explore the feasibility of establishing supplementary surveillance for COVID-19. Methods: Sewage specimens were collected from six sites in Mumbai, India, using the grab sample method and processed using polyethylene glycol (PEG)-dextran phase separation method for virus concentration. Real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the presence of SARS-CoV-2 RNA. Results: A total of 20 sewage samples collected from six different wards in Mumbai city, before the spread of SARS-CoV-2 infections and during May 11-22, 2020, were processed using the phase separation method. The WHO two-phase PEG-dextran method was modified during standardization. SARS-CoV-2 was found to concentrate in the middle phase only. All samples collected before March 16, 2020 were SARS-CoV-2 negative. Viral RNA was detected in sewage samples collected during the ongoing COVID-19 pandemic in all the six wards. Interpretation & conclusions: PEG-dextran phase separation method was effectively used to concentrate SARS-CoV-2 from domestic waste waters to detection levels. It would be feasible to initiate sewage surveillance for SARS-CoV-2 to generate data about the viral transmission in various epidemiologic settings.
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Phylogenetic classification of the whole-genome sequences of SARS-CoV-2 from India & evolutionary trends p. 166
Varsha Potdar, Veena Vipat, Ashwini Ramdasi, Santosh Jadhav, Jayashri Pawar-Patil, Atul Walimbe, Sucheta S Patil, Manohar L Choudhury, Jayanthi Shastri, Sachee Agrawal, Shailesh Pawar, Kavita Lole, Priya Abraham, Sarah Cherian, ICMR-NIV NIC Team
DOI:10.4103/ijmr.IJMR_3418_20  
Background & objectives: Several phylogenetic classification systems have been devised to trace the viral lineages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV-2 strains circulating in India. Methods: The whole genomes of 330 SARS-CoV-2 samples were sequenced using next-generation sequencing (NGS). Phylogenetic and sequence analysis of a total of 3014 Indian SARS-CoV-2 sequences from 20 different States/Union Territories (January to September 2020) from the Global Initiative on Sharing All Influenza Data (GISAID) database was performed to observe the clustering of Nextstrain and Phylogenetic Assignment of Named Global Outbreak LINeages (Pangolin) lineages with the GISAID clades. The identification of mutational sites under selection pressure was performed using Mixed Effects Model of Evolution and Single-Likelihood Ancestor Counting methods available in the Datamonkey server. Results: Temporal data of the Indian SARS-CoV-2 genomes revealed that except for Uttarakhand, West Bengal and Haryana that showed the circulation of GISAID clade O even after July 2020, the rest of the States showed a complete switch to GR/GH clades. Pangolin lineages B.1.1.8 and B.1.113 identified within GR and GH clades, respectively, were noted to be indigenous evolutions. Sites identified to be under positive selection pressure within these clades were found to occur majorly in the non-structural proteins coded by ORF1a and ORF1b. Interpretation & conclusions: This study interpreted the geographical and temporal dominance of SARS-CoV-2 strains in India over a period of nine months based on the GISAID classification. An integration of the GISAID, Nextstrain and Pangolin classifications is also provided. The emergence of new lineages B.1.1.8 and B.1.113 was indicative of host-specific evolution of the SARS-CoV-2 strains in India. The hotspot mutations such as those driven by positive selection need to be further characterized.
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Modelling the spread of SARS-CoV-2 pandemic - Impact of lockdowns & interventions Highly accessed article p. 175
Manindra Agrawal, Madhuri Kanitkar, M Vidyasagar
DOI:10.4103/ijmr.IJMR_4051_20  PMID:33146155
Background & objectives: To handle the current COVID-19 pandemic in India, multiple strategies have been applied and implemented to slow down the virus transmission. These included clinical management of active cases, rapid development of treatment strategies, vaccines computational modelling and statistical tools to name a few. This article presents a mathematical model for a time series prediction and analyzes the impact of the lockdown. Methods: Several existing mathematical models were not able to account for asymptomatic patients, with limited testing capability at onset and no data on serosurveillance. In this study, a new model was used which was developed on lines of susceptible-asymptomatic-infected-recovered (SAIR) to assess the impact of the lockdown and make predictions on its future course. Four parameters were used, namely β, γ, η and ε. β measures the likelihood of the susceptible person getting infected, and γ denotes recovery rate of patients. The ratio β/γ is denoted by R0 (basic reproduction number). Results: The disease spread was reduced due to initial lockdown. An increase in γ reflects healthcare and hospital services, medications and protocols put in place. In Delhi, the predictions from the model were corroborated with July and September serosurveys, which showed antibodies in 23.5 and 33 per cent population, respectively. Interpretation & conclusions: The SAIR model has helped understand the disease better. If the model is correct, we may have reached herd immunity with about 380 million people already infected. However, personal protective measures remain crucial. If there was no lockdown, the number of active infections would have peaked at close to 14.7 million, resulted in more than 2.6 million deaths, and the peak would have arrived by June 2020. The number of deaths with the current trends may be less than 0.2 million.
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CORRESPONDENCES Top

Prediction of potential small interfering RNA molecules for silencing of the spike gene of SARS-CoV-2 p. 182
Kingshuk Panda, Kalichamy Alagarasu, Sarah S Cherian, Deepti Parashar
DOI:10.4103/ijmr.IJMR_2855_20  PMID:33273154
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SARS-CoV-2 & influenza A virus co-infection in an elderly patient with pneumonia p. 190
Ashok Munivenkatappa, Pragya D Yadav, K Swetha, Manjunatha Jayaswamy, Dimpal A Nyayanit, Rima Rakeshkumar Sahay, TJ Basavaraj
DOI:10.4103/ijmr.IJMR_2711_20  PMID:33433500
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Inactivation of SARS-CoV-2 by gamma irradiation p. 196
Rajlaxmi Jain, Prasad Sarkale, Deepak Mali, Anita M Shete, Deepak Y Patil, Triparna Majumdar, Annasaheb Suryawanshi, Savita Patil, Sreelekshmy Mohandas, Pragya D Yadav
DOI:10.4103/ijmr.IJMR_2789_20  PMID:33243957
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Impact of the COVID-19 pandemic on clinical ophthalmology p. 199
Bharat Gurnani, Kirandeep Kaur
DOI:10.4103/ijmr.IJMR_3883_20  PMID:33473015
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Authors’ response p. 200
Parul Chawla Gupta, Praveen Kumar M, Jagat Ram
DOI:10.4103/0971-5916.307214  PMID:33473016
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Modelling the spread of SARS-CoV-2 pandemic - Is this even close to a supermodel? p. 201
Somdatta Sinha
DOI:10.4103/ijmr.IJMR_4525_20  PMID:33510053
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Authors' response p. 204
Manindra Agrawal, Madhuri Kanitkar, M Vidyasagar
DOI:10.4103/0971-5916.307699  
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POLICY Top

Seroprevalence of antibodies to SARS-CoV-2 in healthcare workers & implications of infection control practice in India p. 207
Ritu Gupta, Tanima Dwivedi, Smeeta Gajendra, Biswajeet Sahoo, Sanjeev Kumar Gupta, H Vikas, Angel Rajan Singh, Anant Mohan, Sushma Bhatnagar, Sheetal Singh, Laxmitej Wundavalli, Randeep Guleria
DOI:10.4103/ijmr.IJMR_3911_20  PMID:33642348
Background & objectives: Healthcare workers (HCWs) are considered to be at a high risk of contracting COVID-19 infection. Besides, control of nosocomial infections transmitted from HCWs to the patients is also a cause of concern. This study was undertaken to investigate the seroprevalence of antibodies against the SARS-CoV-2 virus among the hospital staff of a tertiary care health facility in north India. Methods: The HCWs were tested for SARS-CoV-2 serology (IgG+IgM) using chemiluminescence immunoassay between June 22 and July 24, 2020. Venous blood (2 ml) was collected and tested for SARS-CoV-2 IgG and IgM antibodies. Results: Of the 3739 HCWs tested, 487 (13%) were positive for total SARS-CoV-2 antibodies. The highest seroprevalence was observed in administrative staff (19.6%) and least in physicians (5.4%). The staff who used public (20%) and hospital transportation (16.9%) showed higher seroprevalence compared to staff using personal transportation (12.4%). No difference was observed between HCWs posted in COVID versus non-COVID areas. All seropositive symptomatic HCWs in our study (53.6%) had mild symptoms, and the remaining 46.4 per cent were asymptomatic. The antibody positivity rate progressively increased from 7.0 per cent in the first week to 18.6 per cent in the fourth week during the study. Interpretation & conclusions: The presence of antibodies to SARS-CoV-2 in a significant number of asymptomatic HCWs, association with the use of public transport, relatively lower seroprevalence compared with the non-HCWs and rising trend during the period of the study highlight the need for serosurveillance, creating awareness for infection control practices including social distancing and study of infection dynamics in the community for effective control of an infectious pandemic.
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PROGRAMME Top

COVID-19 & HIV/AIDS pandemics: Parallels & lessons p. 214
Natasha Dawa, Jai Prakash Narain
DOI:10.4103/ijmr.IJMR_2598_20  PMID:33243956
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Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis p. 219
Atiya R Faruqui, Denis Xavier, Sandhya K Kamat, Sujith J Chandy, Bikash Medhi, Raakhi K Tripathi, Yashashri C Shetty, John Michael Raj, Sandeep Kaushal, S Balakrishnan, Shubham Atal, Santanu K Tripathi, Dinesh K Badyal, Harihar Dikshit, Sukalyan Saha Roy, Niyati Trivedi, Suparna Chatterjee, Chetna Desai, CD Tripathi, Nirmala N Rege, Pooja Gupta, R Raveendran, Rajni Kaul, Nilima A Kshirsagar
DOI:10.4103/ijmr.IJMR_2294_20  
Background & objectives: Hydroxychloroquine (HCQ), reported to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in in vitro studies, has been recommended for prophylaxis of COVID-19 in healthcare workers (HCWs). The objective of this study was to assess short-term adverse events (AEs) of HCQ in HCWs. Methods: This cross-sectional study among consenting HCWs taking prophylaxis and working in hospitals with COVID-19 patients used online forms to collect details of HCWs, comorbidities, prophylactic drugs used and AEs after the first dose of HCQ. Verification of dose and AEs was done by personal contact. Multivariate logistic regression analysis was done to determine the effect of age, gender and dose of HCQ on AE. Results: Of the 1303 HCWs included, 98.4 per cent (n=1282) took HCQ and 66 per cent (n=861) took 800 mg as first day's dose. Among the 19.9 per cent (n=259) reporting AEs, 1.5 per cent (n=20) took treatment for AE, none were hospitalized and three discontinued HCQ. Gastrointestinal AEs were the most common (172, 13.2%), with less in older [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.89], with more in females (OR 2.46, 95% CI 1.78-3.38) and in those taking a total dose of 800 mg on day one compared to a lower dose. Hypoglycaemia (1.1%, n=14), cardiovascular events (0.7%, n=9) and other AEs were minimal. Interpretation & conclusions: HCQ prophylaxis first dose was well tolerated among HCWs as evidenced by a low discontinuation. For adverse effects, a small number required treatment, and none required hospitalization. The study had limitations of convenience sampling and lack of laboratory and electrocardiography confirmation of AEs.
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Feasibility, efficiency & effectiveness of pooled sample testing strategy (pooled NAAT) for molecular testing of COVID-19 p. 227
Shantanu Prakash, Om Prakash, Hricha Mishra, Danish N Khan, Suruchi Shukla, Ajay Pandey, Kiran Rade, Nivedita Gupta, M.L.B. Bhatt, Amita Jain
DOI:10.4103/ijmr.IJMR_2333_20  
Background & objectives: During the current COVID-19 pandemic, a large number of clinical samples were tested by real-time PCR. Pooling the clinical samples before testing can be a good cost-saving and rapid alternative for screening large populations. The aim of this study was to compare the performance characteristics, feasibility and effectiveness of pooling nasal swab and throat swab samples for screening and diagnosis of SARS-CoV-2. Methods: The pool testing was applied on a set of samples coming from low COVID-19 positivity areas. A total of 2410 samples were tested in pools of five samples each. A total of five pools of five samples each were generated and tested for E gene. Results: Of the total of 482 pools (2410 samples) 24 pools flagged positive. Later on pool de-convolution, a total of 26 samples were detected as positive for COVID-19, leading to positivity of about one per cent in the test population. For the diagnosis of individual samples, the pooling strategies resulted in cost savings of 75 per cent (5 samples per pool). Interpretation & conclusions: It was observed that testing samples for COVID-19 by reverse transcription (RT)- PCR after pooling could be a cost-effective method which would save both in manpower and cost especially for resource-poor countries and at a time when test kits were short in supply.
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PRACTICE Top

Face mask - An essential armour in the fight of India against COVID-19 p. 233
Samiran Panda, Harkiran Kaur, Lalit Dandona, Balram Bhargava
DOI:10.4103/ijmr.IJMR_4486_20  PMID:33533732
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Focussing on ‘mental hygiene’ along with ‘hand hygiene’ in the times of COVID-19 p. 238
Mahadev Singh Sen, Nishtha Chawla, Rajesh Sagar
DOI:10.4103/ijmr.IJMR_2960_20  PMID:33273153
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