A case control investigation of COVID-19 associated Mucormycosis in India (preprint)

Background: Increased occurrence of mucormycosis in India during the second wave of the COVID-19 pandemic in early 2021 in India subsequently prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of Covid-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with it.Methods: Eleven study sites were involved across India and archived records since 1st January till 30th September, 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. Results: Admitted CAM-case number reached highest point in May 2021 after a month of peak admission for COVID-19. Odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95%CI: 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95%CI: 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95%CI: 1.02, 1.11) and use of methyl prednisolone (aOR: 2.71, 95%CI: 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95%CI: 0.08, 0.41). Genomic sequencing of archived respiratory samples showed similar presence of Delta and Delta derivates in both cases and controls.Conclusions: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients bear the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to prevention efforts.  

Vaccination saves lives: How do patients with chronic diseases and severe COVID-19 fare? Analysis from India’s National Clinical registry for COVID-19 (preprint)

Objectives This study aims to describe the demographic and clinical profile and ascertain the determinants of outcome among hospitalised COVID-19 adult patients enrolled in the National Clinical Registry for COVID-19 (NCRC). Methods NCRC is an on-going data collection platform operational in 42 hospitals across India. Data of hospitalized COVID-19 patients enrolled in NCRC between 1 st September 2020 to 26 th October 2021 were examined. Results Analysis of 29,509 hospitalised, adult COVID-19 patients [mean (SD) age: 51.1 (16.2) year; male: 18752 (63.6%)] showed that 15678 (53.1%) had at least one comorbidity. Among 25715 (87.1%) symptomatic patients, fever was the commonest symptom (72.3%) followed by shortness of breath (48.9%) and dry cough (45.5%). In-hospital mortality was 14.5% (n=3957). Adjusted odds of dying were significantly higher in age-group ≥60 years, males, with diabetes, chronic kidney diseases, chronic liver disease, malignancy, and tuberculosis, presenting with dyspnea and neurological symptoms. WHO ordinal scale 4 or above at admission carried the highest odds of dying [5.6 (95% CI: 4.6, 7.0)]. Patients receiving one [OR: 0.5 (95% CI: 0.4, 0.7)] or two doses of anti-SARS CoV-2 vaccine [OR: 0.4 (95% CI: 0.3, 0.7)] were protected from in-hospital mortality. Conclusions WHO ordinal scale at admission is the most important independent predictor for in-hospital death in COVID-19 patients. Anti-SARS-CoV2 vaccination provides significant protection against mortality.

Analysis of predictors and outcomes of COVID-19 patients requiring ICU admission from COVID 19 (preprint)

BackgroundSevere Corona virus disease (COVID-19) is associated with high mortality. Although single centre intensive care units (ICU) have reported clinical characteristics and outcomes, no large scale multicentric study from India has been published. The present retrospective, multi-centre study was aimed to describe the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian council of Medical Research (ICMR), India.MethodsProspectively collected data from multiple participating institutions was entered in the electronic National Clinical Registry of COVID 19. We enrolled patients aged>18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative RT PCR, death within 24 hours of ICU admission, or patients with incomplete data in the registry Their demographic characteristics, laboratory variables, ICU severity indices, treatment strategies and outcomes were analysed.ResultsA total of 5865 patients, with mean age 56±15 years, with 3840/5865 (65.4%) men, were enrolled in the ICMR registry.. Overall mortality was 2535/5865 (43.5%). Non-survivors were older than survivors (58.2±15.4 years vs 53.6 ±14.7 years; P=0.001). Non-survivors had multiple comorbidities (n=1951, 52.9%) with hypertension (47.2%) and diabetes (45.6%) being the most common, higher creatinine (1.6 ± P=0.001, high D-dimer (1.56 vs 1.37, P=0.001), higher CT severity index (16.8±5.2 vs 13.5 ±5.47 ) compared to  survivors. Non survivors had longer hospital and ICU stay (P=0.001). On multivariate regression analysis, high NLR (HR 1.017, 95% CI 1.005- 1.029, P=0.001), high CRP (HR 1.008, 95% CI 1.006- 1.010, P=0.001), high D dimer ((HR 1.089, 95% CI 1.065- 1.113, P=0.001) were associated with mechanical ventilation while younger age, (HR 0.974, CI 0.965-0.983, p=0.001), high D dimer (HR-1.014, CI 1.001-1.027, P=0.035) and use of prophylactic LMWH (HR 0.647, CI 0.527-0.794, p=0.001) were independently associated with mortality. ConclusionIn this large retrospective study of 5865 critically ill COVID 19 patients admitted to ICU, overall mortality was 2535/5865 (43.5%). Age, high D dimer, CT Severity score and use of prophylactic LMWH were independently associated with mortality. 

Delta Variant SARS-CoV-2 infections in pediatric cases during the second wave in India (preprint)

The aim of this study was to identify the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n=583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021.Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Analysis of the COVID-19 Testing Parameters and Progression of the Pandemic at the District Level- Findings from the Icmr- Hundred Million Test (HMT) Database During the First Wave in India (preprint)

Background: India has the second highest number of COVID-19 cases. We evaluated the progression of the pandemic across the lockdowns and phased reopening during the first wave in India at the district level.Methods: More than 100 million COVID-19 test results along with other parameters available in the Indian Council of Medical Research (ICMR) database during March-October, 2020, was used for the analysis. District was chosen as the unit of analysis, as it is the smallest unit of administration in India. The districts were stratified as high, moderate, and low case load districts, and data analysis was done for each phase of lockdown.Findings: Of the 110.5 million tests included in the analysis, 54.79 million tests were performed using molecular methods, 53.58 million by rapid antigen tests (RATs) and 2.13 million by the indigenous TruNat platform. Only 7.95 million (7.16%) tests were among symptomatic individuals. The positivity proportion among symptomatic individuals (22.6%) was significantly higher than asymptomatic individuals (8.6%). The tests conducted, and positivity proportions were significantly higher in high caseload districts and 58% of these tests were by molecular methods as opposed to only one-third in low case load districts. The proportion of ‘symptomatic contacts’ being tested increased significantly around the peak.Interpretation: Laboratory parameters, along with other demographic information, can help us better understand the spread of the pandemic in a country. Such information can be crucial to formulate and implement public health policies in any future waves of the pandemic.Funding: Indian Council of Medical Research (ICMR)Declaration of Interest: We declare no competing interestsEthical Approval: Approval from the ICMR Central Ethics Committee on Human Research (Ref. No.NCDIR/BEU/ICMR-CECHR/75/2020) was obtained for this study and no patient identifierswere accessed during analysis or reporting.

RNA-extraction-free diagnostic method to detect SARS-CoV-2: an assessment from two States, India (preprint)

With increasing demand for large numbers of testing during COVID-19 pandemic, came alternative protocols with shortened turn-around time. We evaluated the performance of such an approach wherein 1138 consecutive clinic attendees were enrolled; 584 and 554 respectively from two independent study sites in the cities of Pune and Kolkata. Paired nasopharyngeal and oropharyngeal swabs were tested by using both reference and index methods in blinded fashion. Prior to conducting RT-PCR, swabs collected in viral transport medium (VTM) were processed for RNA extraction (reference method) and swabs collected in dry tube without VTM were incubated in Tris-EDTA-Proteinase K buffer for 30 minutes and heat inactivated at 98{degrees}C for 6 minutes (index method). Overall sensitivity and specificity of the index method were 78.9% (95% CI 71% to 86%) and 99 % (95% CI 98% to 99.6%) respectively. Agreement between the index and reference method was 96.8 % (k = 0.83, SE=0.030). The reference method exhibited enhanced detection of viral genes (E, N and RdRP) with lower Ct values compared to the index method. The index method can be used for detecting SARS-CoV-2 infection with appropriately chosen primer-probe set and heat treatment approach in pressing time; low sensitivity constrains its potential wider use.

Serendipitous COVID-19 Vaccine-Mix in Uttar Pradesh, India: Safety and Immunogenicity Assessment of a Heterologous Regime (preprint)

Immunization program against COVID-19 in India started with two vaccines; AstraZenecas ChAdOx1-nCov-19 (termed Covishield in India) and inactivated whole virion BBV152 (Covaxin); homologous prime-boost approach was followed. However, eighteen individuals, under the national program, inadvertently received Covishield as the first jab and Covaxin as the second. We compared the safety and immunogenicity profile of them against that of individuals receiving either Covishield or Covaxin (n=40 in each group). Lower and similar adverse events following immunization in all three groups underlined the safety of the combination vaccine-regime. Immunogenicity profile against Alpha, Beta and Delta variants in heterologous group was superior; IgG antibody and neutralising antibody response of the participants was also significantly higher compared to that in the homologous groups. The findings suggest that immunization with a combination of an adenovirus vector platform-based vaccine followed by an inactivated whole virus vaccine was not only safe but also elicited better immunogenicity.

Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152 (preprint)

The recent emergence of the SARS-CoV-2 Variant of Concern B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152 a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individuals full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID- 19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.

Association Between Ambient Air Pollutants and Meteorological Factors With SARS-CoV-2 Transmission and Mortality in India: an Exploratory Study (preprint)

Background: The Coronavirus disease 2019 (COVID-19) pandemic poses a serious public health concern worldwide. Certain regions of the globe were severely affected in terms of prevalence and mortality than other. Although the cause for this pattern is not clearly understood, lessons learned from previous epidemics and emerging evidences suggest the major role of ecological factors like ambient air pollutants (AAP) and meteorological parameters in increased COVID-19 incidence. The present study aimed to understand the impact of these factors on SARS-CoV-2 transmission and their associated mortality in major cities of India.Methods: This study used secondary AAP, meteorological and COVID-19 data from official websites for the period January-November 2020, which were divided into Pre-lockdown (January-March 2020), Phase I (April to June 2020) and Phase II (July to November 2020). After comprehensive screening, five major cities that includes 48 CPCB monitoring stations collecting daily data of ambient temperature, particulate matter PM2.5 and 10 were analysed. Spearman and Kendall’s rank correlation test was performed to understand the association between SARS-CoV-2 transmission and AAP and, meteorological variables. Similarly, case fatality rate (CFR) was determined to compute the correlation between AAP and COVID-19 related morality.Results: The level of air pollutants in major cities were significantly reduced during Phase I compared to Pre-lock down and increased upon Phase II in all the cities. During the Phase II in Delhi, the strong significant positive correlation was observed between the AAP and SARS-CoV-2 transmission. However, in Bengaluru, Hyderabad, Kolkata and Mumbai AAP levels were moderate and no correlation was noticed. The relation between AT and SARS-CoV-2 transmission was inconclusive as both positive and negative correlation observed. In addition, Delhi and Kolkata showed a positive association between long-term exposure to the AAP and COVID-19 CFR.  Conclusion: Our findings support the hypothesis that the particulate matter upon exceeding the satisfactory level serves as an important cofactor in increasing the risk of SARS-CoV-2 transmission and related mortality. These findings would help public health experts to understand the SARS-CoV-2 transmission against ecological variables in India and provides supporting evidence to healthcare policymakers and government agencies for formulating strategies to combat the COVID-19.

Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial (preprint)

BackgroundWe report the clinical efficacy against COVID-19 infection of BBV152, a whole-virion inactivated SARS-CoV-2 vaccine formulated with a Toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG). MethodsWe did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18-98 years) randomised 1:1 using a computer-generated randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory-confirmed symptomatic COVID-19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in sub-groups for age (18-< 60 years and [≥] 60 years) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots. FindingsBetween November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0{middle dot}77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77{middle dot}8% (95% CI: 65{middle dot}2-86{middle dot}4). Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93{middle dot}4% (57{middle dot}1-99{middle dot}8). Efficacy against asymptomatic COVID-19 was 63{middle dot}6% (29{middle dot}0-82{middle dot}4). BBV152 conferred 65{middle dot}2% (95% CI: 33{middle dot}1-83{middle dot}0) protection against the SARS-CoV-2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported. InterpretationBBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID-19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines. FundingThis work was supported and funded by Bharat Biotech International Limited and partly co-funded by the Indian Council of Medical Research. Clinicaltrials.gov: NCT04641481

Neutralization of Delta variant with sera of Covishield vaccinees and COVID-19 recovered vaccinated individuals (preprint)

The recent emergence of B.1.617 lineage has created grave public health problem in India. The lineage further mutated to generate sub-lineages B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3. Apparently, the Delta variant has slowly dominated the other variants including B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3. With this, World Health Organization has described this sub-lineage as variant of concern. The high transmissibility associated with Delta variant has led to second wave of pandemic in India which affected millions of people. Besides this, variant of concerns has been reported to show lower neutralization to several approved vaccines. This has led to breakthrough infections after completion of vaccination regimen. There is limited information available on the duration of protective immune response post-infection, vaccination or breakthrough infection with SARS-CoV-2. In this study, we have evaluated immune response in sera of the Covishield vaccinated individuals belonging to category: I. one dose vaccinated, II. two doses vaccinated, III. COVID-19 recovered plus one dose vaccinated, IV. COVID-19 recovered plus two doses vaccinated and V. breakthrough COVID-19 cases. The findings of the study demonstrated that the breakthrough cases and the COVID-19 recovered individuals with one or two dose of vaccine had relatively higher protection against Delta variant in comparison to the participants who were administered either one or two doses of Covishield. Prior vaccination results in less severe disease against subsequent infection provide evidence that both humoral and cellular immune response play an important role in protection.

Neutralization against B.1.351 and B.1.617.2 with sera of COVID-19 recovered cases and vaccinees of BBV152 (preprint)

Recently, multiple SARS-CoV-2 variants have been detected across the globe.The recent emergence of B.1.617 lineage has created serious public health problem in India. The high transmissibility was observed with this lineage which has led to daily increase in the number of SARS-CoV-2 infections. Apparently, the sub-lineage B.1.617.2 has slowly dominated the other variants including B1617.1, B.617.3 and B.1.1.7. With this, World Health Organization has described B.1.617.2 as variant of concern. Besides this, variant of concern B.1.351 has been also reported from India, known to showreducedefficacyfor many approved vaccines. With the increasing threat of the SARS-CoV-2 variants, it is imperative to assess the efficacy of the currently available vaccines against these variants. Here, we have evaluated the neutralization potential of sera collected from COVID-19 recovered cases (n=20) and vaccinees with two doses of BBV152 (n=17) against B.1.351 and B.1.617.2 compared to the prototype B.1 (D614G) variant.The finding of the study demonstrated a reduction in neutralization titers with sera of COVID-19 recovered cases(3.3-fold and 4.6-fold) and BBV152 vaccinees (3. 0 and 2.7 fold) against B.1.351 and B.1.617.2 respectively. Although, there is reduction in neutralization titer, the whole-virion inactivated SARS-CoV-2 vaccine (BBV152) demonstrates protective response against VOC B.1351 and B.1.617.2.

Isolation of SARS-CoV-2 B.1.1.28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model (preprint)

Background: Considering the potential threat from emerging SARS-CoV-2 variants and the rising COVID-19 cases, SARS-CoV-2 genomic surveillance is ongoing in India. We report herewith the isolation of the P.2 variant (B.1.1.28.2) from international travelers and further its pathogenicity evaluation and comparison with D614G variant (B.1) in hamster model. Methods: Virus isolation was performed in Vero CCL81 cells and genomic characterization by next generation sequencing. The pathogenicity of the isolate was assessed in Syrian hamster model and compared with B.1 variant. Results: B.1.1.28.2 variant was isolated from nasal/throat swabs of international travelers returned to India from United Kingdom and Brazil. The B.1.1.28.2 variant induced body weight loss, viral replication in the respiratory tract, lung lesions and caused severe lung pathology in infected Syrian hamster model in comparison, with B.1 variant infected hamsters. The sera from B.1.1.28.2 infected hamsters efficiently neutralized the D614G variant virus whereas 6-fold reduction in the neutralization was seen in case of D614G variant infected hamsters sera with the B.1.1.28.2 variant. Conclusions: B.1.1.28.2 lineage variant could be successfully isolated and characterization could be performed. Pathogenicity of the isolate was demonstrated in Syrian hamster model and in comparison, with B.1 variant was found more pathogenic. The findings of increased disease severity and neutralization reduction is of great concern and point towards the need for screening the vaccines for efficacy.

Neutralization potential of Covishield vaccinated individuals against B.1.617.1 (preprint)

Covishield comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to responsible for surge of the cases in India. The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naive subjects (n=43) and COVID-19 recovered subjects (n=18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p<0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.

INDIA'S PRAGMATIC VACCINATION STRATEGY AGAINST COVID-19: A MATHEMATICAL MODELLING BASED ANALYSIS (preprint)

ObjectivesTo investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India. DesignMathematical modelling. SettingsIndian epidemic of COVID-19 and vulnerable population. Data sourcesCountry specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain. ModelAn age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed. InterventionsComparison of different vaccine strategies by targeting priority groups such as key workers including health care professionals, individuals with comorbidities (24 - 60 year), and all above 60. Main outcome measuresIncidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented. ResultsThe priority groups together account for about 18% of Indias population. An infection preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (CrI) 16.7 - 25.4), and cumulative mortality by 29.7% (95% CrI 25.8-33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4 - 13.0), and cumulative mortality by 32.9% (95% CrI 28.6 - 37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are > 60, and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely-populated rural areas, those with comorbidities should be prioritised after keyworkers. ConclusionsAn appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogenity. Smart vaccination, based on public health considerations, rather than mass vaccination, appears prudent. O_TEXTBOXStrengths and limitation of this study O_LIThe model in this study is informed by age-dependent risk factors for SARS-CoV-2 infection among contacts, and is stratified by co-morbidities (diabetes and/or hypertension), and vaccination status. C_LIO_LIData on mortality and large-scale contact tracing from within India, and the recent national sero-survey results were used, which constituted a major strength of this investigation. C_LIO_LIDistinguishing between infection and symptomatic disease preventing vaccines, the model was simulated under a range of scenarios for the basic reproduction number (R0). C_LIO_LIShould they have been available, real life country-specific data on excess risks of deaths due to comorbidities would have added strength to the presented model. C_LIO_LIKey priority group-specific data on social mixing and potential associated transmission was not available, and remained as a limitation. C_LI C_TEXTBOX

SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant (preprint)

Background: The recent emergence of new SARS-CoV-2 lineage B.1.617 in India has been associated with a surge in the number of daily infections. This variant has combination of specific mutations L452R, E484Q and P681R reported to possibly enhance the transmissibility with likelihood of escaping the immunity. We investigated the viral load and pathogenic potential of B.1.617.1 in Syrian golden hamsters. Methods: Two groups of Syrian golden hamsters (9 each) were inoculated intranasally with SARS CoV-2 isolates, B.1 (D614G) and B.1.617.1 respectively. The animals were monitored daily for the clinical signs and body weight. The necropsy of three hamsters each was performed on 3, 5- and 7-days post-infection (DPI). Throat swab (TS), nasal wash (NW) and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2 specific Real-time RT-PCR. Results: The hamsters infected with B.1.617.1 demonstrated increased body weight loss compared to B.1 variant. The highest viral load was observed in nasal turbinate and lung specimens of animals infected with B.1.167.1 on 3 DPI. Neutralizing antibody (NAb) and IgG response in hamsters of both the groups were observed from 5 and 7 DPI respectively. However, higher neutralizing antibody titers were observed against B.1.167.1. Gross pathology showed pronounced lung lesions and hemorrhage with B.1.671 compared to B.1. Conclusions: B.1617.1 and B.1 variant varied greatly in their infectiousness, pathogenesis in hamster model. This study demonstrates higher pathogenicity in hamsters evident with reduced body weight, higher viral load in lungs and pronounced lung lesions as compared to B.1 variant.

Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine (preprint)

The emergence of new SARS-CoV-2 variants has been a serious threat to the public health system and vaccination program. The variant of concerns have been the under investigation for their neutralizing potential against the currently available COVID-19 vaccines. Here, we have determined the neutralization efficacy of B.1.1.28.2 variant with the convalescent sera of individuals with natural infection and BBV152 vaccination. The two-dose vaccine regimen significantly boosted the IgG titer and neutralizing efficacy against both B.1.1.28.2 and D614G variants compared to that seen with natural infection. The study demonstrated 1.92 and 1.09 fold reductions in the neutralizing titer against B.1.1.28.2 variant in comparison with prototype D614G variant with sera of vaccine recipients and natural infection respectively.

Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India (preprint)

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of variants of concern (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to selected monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation is warranted for accessing both ACE2 binding and the effectiveness of commonly elicited neutralizing mAbs for the strains of lineage B.1.617. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.