Reinfection or reactivation: Genome‐based two distinct SNP profile of SARS‐CoV2 repositivity in an Indian case (original) (raw)
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Frontiers in Medicine, 2021
Background: SARS-CoV-2 infection may not provide long lasting post-infection immunity. While hundreds of reinfections have reported only a few have been confirmed. Whole genome sequencing (WGS) of the viral isolates from the different episodes is mandatory to establish reinfection.Methods: Nasopharyngeal (NP), oropharyngeal (OP) and whole blood (WB) samples were collected from paired samples of four individuals who were suspected of SARS-CoV-2 reinfection based on distinct clinical episodes and RT-PCR tests. Details from their case record files and investigations were documented. RNA was extracted from the NP and OP samples and subjected to WGS, and the nucleotide and amino acid sequences were subjected to genome and protein-based functional annotation analyses. Serial serology was performed for Anti-N IgG, Anti- S1 RBD IgG, and sVNT (surrogate virus neutralizing test).Findings: Three patients were more symptomatic with lower Ct values and longer duration of illness. Seroconversion ...
2021
Background: In recent months, multiple cases of confirmed SARS-CoV-2 reinfection have been reported. However, accurate epidemiological and virological data, including genomic analysis where possible, are required to differentiate cases of prolonged viral RNA shedding (i.e. intermittent detection) from true reinfection. The objective of this review was to systematically identify and summarise all cases of SARS-CoV-2 reinfection confirmed by comparative genomic analysis. Methods: A protocol based on Cochrane rapid review methodology was employed. Databases and pre-print servers were searched until 9/11/2020. Results: Ten studies, representing 17 patients, were identified (mean age = 40; 71% male). The time interval between primary infection and reinfection ranged from 13 to 142 days (median: 60). Comparative whole genome sequencing confirmed reinfection in 14 patients (the primary and secondary infections were caused by different viruses). A further three cases had strong, but not confirmed evidence of reinfection, as only partial genomes were retrieved on primary infection. Across 12 studies that reported the number of single nucleotide polymorphisms (SNPs) comparing the first and second genomes, between 8 and 24 SNPs were discovered. With an average SARS-CoV-2 mutation acquisition rate of 1-2 per month, in all cases it is likely that the secondary infection was caused by a different SARS-CoV-2 virus, rather than prolonged shedding of viral RNA from the primary infection.
Genomic analysis of SARS-CoV-2 breakthrough infections from Varanasi, India
2021
Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2. However, there are growing laboratory reports that the newer variants of concerns (VOCs e.g. Alpha, Beta, Delta etc) may evade vaccine induced defense. In addition to that, there are few ground reports on health workers having breakthrough infections. In order to understand VOC driven breakthrough infection we investigated 14 individuals who tested positive for SARS-CoV-2 after being administered a single or double dose of Covishield (ChAdOx1, Serum Institute of India) from the city of Varanasi, which is located in the Indian state of Uttar Pradesh. Genomic analysis revealed that 78.6% (11/14) of the patients were infected with the B.1.617.2 (Delta) variant. Notably, the frequency (37%) of this variant in the region was significantly lower (p<0.01), suggesting that the vaccinated people were asymmetrically infected with the Delta variant. Most of the patients tested displayed mild sy...
Virus Genes, 2021
In view of the rapidly progressing COVID-19 pandemic, our aim was to isolate and characterize SARS-CoV-2 from Indian patients. SARS-CoV-2 was isolated from nasopharyngeal swabs collected from the two members of a family without any history of (H/O) travel abroad. Both the virus isolates (8003 and 8004) showed CPE on day 3 post-inoculation, viral antigens by immunofluorescence assay and produced distinct, clear and uniform plaques. Infectious virus titers were 5 × 10 6 and 4 × 10 6 Pfu/ml by plaque assay and 10 7.5 and 10 7 by CPE-based TCID50/ml, respectively. Phylogenetic analysis grouped our isolates with the Italian strains. On comparison with Wuhan strain, 3 unique mutations were identified in nsp3 (A1812D), exonuclease (P1821S) of Orf1ab and spike protein (Q677H) regions, respectively. Both the viruses grouped with Italian strains of SARS-CoV-2 suggesting possible source being the virus imported from Italy. These fully characterized virus isolates will be useful in developing neutralization/virological assays for the evaluation of vaccines/antivirals.
SARS-CoV-2 variants of concern are emerging in India
Nature Medicine
SARS-CoV-2 variants of concern are emerging in India To the Editor-The current outbreak of COVID-19 in India, which started in early March 2021, has created a new world record even beyond the outbreaks in the UK, the United States and Brazil. Prior to March 2021, less than 0.7% of the Indian population was infected with COVID-19. This current second wave took only 2 months to infect an additional ~0.36% of the population, and India is now recording over 0.4 million new cases per day (as of 23 April 2021). The true number is probably even higher, with some estimates putting the number of daily new cases at over 1 million, more than five times the officially recorded number 1. The sudden surge in COVID-19 cases in India coincides with high prevalence of more-transmissible variants, associated with diagnostic test failures and antibody escape 2. These coronavirus SARS-CoV-2 variants of concern-B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (501Y.V3; also known as P.1)-were observed during the sudden surge in COVID-19 cases in the UK, South Africa and Brazil, respectively, with subsequent local transmission across the world 2,3 (Fig. 1a). In India, the frequency of 501Y.V1 is higher than that of 501Y.V2 and 501Y.V.3 (Fig. 1b). The recently designated variant of concern B.1.617 and variant of interest B.1.618 have also been gaining attention in India 3 (Fig. 1a-c). Variant B.1.617.1 shows co-occurrence of three key mutations in sequence encoding the viral spike protein: L452R, E484Q and P681R. L452R raised concerns in the United States as part of the California variants B.1.427 and B.1.429 and conferred resistance to the neutralizing monoclonal antibodies X593 and P2B-2F6 4. E484Q shares antibody-escape features similar to those of mutation E484K, seen in variants 501Y.V2, 501Y.V3 and B.1.618 2. P681R may enhance processing by host proteases by extending the polybasic 'RRAR' motif, which results in a greater viral load and the potential for increased transmission. Another similar variant of concern, B.1.617.2, with mutations L452R, T478K and P681R, is highly prevalent in the state of Gujrat in India 3. There was enrichment for the mutation T478K or T478R when SARS-CoV-2 was subjected to weak neutralizing antibodies, which indicates this mutation may lead to antibody escape. Variant B.1.618, which has the E484K correspondence
Genomic characterization and Epidemiology of an emerging SARS-CoV-2 variant in Delhi, India
2021
Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached a population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and partial reduction of immunity elicited by prior infection (median estimates; ×1.5-fold, 20% reduction). Seropositivity of an employee and family cohort increased from 42% to 86% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi.One-Sentence SummaryDelhi experienced an overwhelming surge of COVID-19 cases and fatalities peaking in May 2021 as the highly transmissible and immune evasiv...
Cureus, 2023
Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global health crisis, with various variants emerging over time. In India, particularly in Maharashtra, a resurgence of cases and distinct transmission patterns have been observed. This study aimed to identify and characterize the circulating SARS-CoV-2 variants during the early second wave in Maharashtra, India. Materials and methods Nasopharyngeal swabs were collected from 24 RT-PCR-positive coronavirus disease of 2019 (COVID-19) cases across four districts of Maharashtra. Whole genome sequencing (WGS) was performed using the ARTIC amplicon sequencing protocol, and the data were analyzed. Results A total of 189 amino-acid mutations were identified across the 24 samples. Compared to the Indian genomes, 44 amino-acid mutations were unique to 24 genomes. Clade 20A was the most prevalent (66.66%), followed by 20B and 21B. The lineage B.1.36 (45.83%) was the most common, followed by B.1.617.1 (16.67%). The D614G mutation was the most frequent spike mutation (95.83%). Four samples from the Amravati district clustered distinctly under Clade 21B with spike mutations E154K in the N-terminal domain (NTD), L452R and E484Q in the receptor-binding domain (RBD) and P681R in proximity to the furin cleavage site. The temporal distribution of samples revealed the presence of Clade 21B in Maharashtra since the 31st of January 2021. Conclusion The study provides valuable insights into the circulating SARS-CoV-2 variants during the early second wave in Maharashtra, highlighting specific clades and mutations. The unique clustering patterns and the high prevalence of immune-escape mutations emphasize the need for continuous monitoring and genomic surveillance.
2021
SummaryBackgroundThe current global pandemic of Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 led to the investigation with clinical, biochemical, immunological and genomic characterization from the patients to understand the pathophysiology of viral infection.MethodsSamples were collected from six asymptomatic and six symptomatic SARS-CoV-2 confirmed hospitalized patients in Bhubaneswar, Odisha, India. Clinical details, biochemical parameters, treatment regime were collected from hospital, viral load was determined by RT-PCR, levels of cytokines and circulating antibodies in plasma were assessed by Bioplex and isotyping respectively. In addition, the whole genome sequencing of viral strains and mutational analysis were carried out.FindingsAnalysis of the biochemical parameters highlighted the increased levels of C-Reactive protein (CRP), lactate dehydrogenase (LDH), serum SGPT, serum SGOT and ferritin in symptomatic patients indicating that patients with higher levels o...
SARS-CoV-2 re-infection: development of an epidemiological definition from India
Epidemiology and Infection, 2021
The current investigation was conducted with the objective to develop an epidemiological case definition of possible severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) re-infection and assess its magnitude in India. The epidemiological case definition for SARS-CoV-2 re-infection was developed from literature review of data on viral kinetics. For achieving second objective, the individuals who satisfied the developed case definition for SARS-CoV-2 re-infection were contacted telephonically. Taking available evidence into consideration, re-infection with SARS-CoV-2 in our study was defined as any individual who tested positive for SARS-CoV-2 on two separate occasions by either molecular tests or rapid antigen test at an interval of at least 102 days with one negative molecular test in between. In this archive based, telephonic survey, 58 out of 1300 individuals (4.5%) fulfilled the above-mentioned definition; 38 individuals could be contacted with healthcare workers (HCWs) a...
Journal of Pure and Applied Microbiology, 2021
SARS-CoV-2 variants rapid emergence has posed critical challenge of higher transmission and immune escape causing serious threats to control the pandemic. The present study was carried out in confirmed cases of SARS-CoV-2 patients to elucidate the prevalence of SARS-CoV-2 variant strain. We performed RT-PCR using extracted RNA from the nasopharyngeal swabs of suspected Covid-19 patients. Confirmed positive cases with CT<25 were subjected to whole-genome sequencing to track the prevalence of the virus in the Malwa region of Punjab. The presence of B.1, B.1.1.7, B.1.351, B.1.617.1, B.1.617.2, AY.1 and other unidentified variants of SARS-CoV-2 was found in the studied population. Among all the variants, B.1.1.7 (UK variant) and B.1.617.2 (delta-Indian variant) was found to be the most dominant variant in the population and was found majorly in Patiala followed by Ludhiana, SBS Nagar, Mansa and Sangrur. In addition to this, sequencing results also observed that the dominant trait was...