CME INDIA Presentation by Admin.

Much awaited COVAT study is now online.

The COVAT Study will complete by September-October 2021. This is the interim result after first dose of COVISHIELD and COVAXIN. It clearly indicates how both these vaccines behaved in antibody response and adverse effect profile. At present, no definite conclusions can be put forward about superiority of any said vaccines. But some emerging data are very interesting to note.

The COVAT Study

What is this Study?

Antibody Response after First-dose of ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) amongst Health Care Workers in India: Preliminary Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study.

Principal Investigators

• Dr Awadhesh Kumar Singh, MD, DM (Kolkata);
• Dr Sanjeev Ratnakar Phatak, MD (Ahmedabad);
• Dr Nagendra Kumar Singh (NK Singh), Dhanbad;
• Dr Arvind Gupta, MD, (Jaipur);
• Dr Arvind Sharma, MD (Jaipur);
• Dr Kingshuk Bhattacharjee, PhD (Kolkata);
• Dr Ritu Singh, MD(Kolkata);

PAN INDIA Study (Includes 22 cities)

Drs. Akash Kumar Singh (Vadodara), Amit Gupta (Noida), Anuj Maheshwari (Lucknow), Arvind Kumar Ojha (Kolkata), Bhavtharini (Erode), B. Harish Kumar (Mysore), J K Sharma (New Delhi), Jayant Panda (Cuttack), Kavya Chand Yalamudi (Guntur), Kiran Shah (Vadodara), M Gowri Sankar (Coimbatore), Manohar KN (Bangalore), Meena Chhabra (New Delhi), Pratap Jethwani (Rajkot), M Shunmugavelu (Trichy), Rajiv Kovil (Mumbai), Sunil Gupta (Nagpur), Subhash Kumar (Patna), Somnath (Hyderabad) and Urman Dhruv(Ahmedabad) are involved in this study as regional co-ordinators.

Why study was planned?

• The Indian national vaccination program started from January 16, 2021 after the approval of two candidate vaccines namely CovishieldTM (ChAdOx1-nCOV or AZD1222, acquired from Oxford University and AstraZeneca, manufactured by Serum Institute of India, Pune) and CovaxinTM (BBV-152, manufactured by Bharat Biotech, Hyderabad
• There is still a paucity of information as to how much and how long, these novel vaccines can elicit an immune response, both at cellular as well as the molecular level.
• It is well-known that a humoral immune response to an acquired infection or vaccination, results in two major immune changes in human.
• The antibodies produced by the antibody secreting cells (ASC) provide a rapid, protective immunity and, the generation of long-lived memory B cells become capable of mounting recall responses whenever re-exposed.
• Available evidence suggests that these immunological memories in the form of antibodies and memory B cells are durable for over 8 months post-SARS-CoV-2 infection although the exact duration of immune protection after the infection or vaccination is currently unknown.
• The antibody kinetics after vaccination with Covishield and Covaxin is less well known. Phase 1/2 studies that have evaluated the kinetics of both short-term binding (against all epitopes such as spike protein, receptor-binding domain and nucleocapsid protein) and neutralizing antibodies have demonstrated a significant rapid increase with both Covishield and Covaxin in vaccinated SARS-CoV-2 naïve as well as SARS-CoV-2 recovered individuals
• There is still limited knowledge about antibody repertoire over the time and its variation and correlation to age, sex, body mass index (BMI), and in presence of comorbidities including its duration and treatment, especially in Indians.
• It is also not yet known whether the antibody kinetics differ between the two vaccines approved in India, after the first and second dose, and thereafter over time.
• The antibody repertoire between the two vaccines in SARS-CoV-2 naïve and SARSCoV-2 recovered individuals is not entirely known in Indians.

COVAT assessed the Gap in Knowledge

• This study assessed the humoral immune response after the first dose of two vaccines ChAdOx1-nCOV.(CovishieldTM) and BBV-152 (CovaxinTM) in Indian health care workers (HCW).
• This is the first ongoing study of unique significance.
• It is a Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study.
• It is being conducted amongst health care workers (HCW, with or without past history of SARS-CoV-2 infection.
• SARS-CoV-2 anti-spike binding antibody is being assessed quantitatively at four timepoints between 21 days or more after the first dose to 6 months after the second dose.
• Primary aim is to analyze antibody response following each dose of both vaccines and its correlation to age, sex, body mass index (BMI) and comorbidities.
• The current publication reports the preliminary results of anti-spike antibody response after the first dose.

What are the preliminary findings?

• 552 subjects received first dose of either of the two vaccines
• The mean age of the participants: 44.8 ± 13.2 years, with 58.9% males and 41.1% females.
• While 23.7% had one or more comorbidities (10.3% T2DM, 17.9% HTN, 4.7% dyslipidemia and 2.3% IHD), the study had no participant having T1DM, CKD or cancer in the study cohort.
• Amongst participants, 10.9% had past history of confirmed SARS-CoV-2 who took the first dose of either of the vaccine
• A total of 552 participants’ data has been analyzed.
• Out of these 456 and 96 received first dose of Covishield and Covaxin respectively.
• Overall, 79.3% had seropositivity and were responders (defined as anti-spike antibody titre ≥15AU/ml measured at day 21 to day before second dose) for antispike antibody.
• Amongst the 552 HCW (325 Male, 227 Female), 456 and 96 received first dose of Covishield and Covaxin respectively.
• Overall, 79.3% showed seropositivity after the first dose. Responder rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (86.8 vs. 43.8%; 61.5 vs. 6 AU/ml; both p<0.001).
• Presence of any comorbidities was associated with a lower responder rate, compared to those without (72.5% vs. 81.5% respectively, p=0.027).
• No association was found between age and antibody response in the overall and Covaxin cohort, however a greater responder rate was elicited in the age ≤60 years for the Covishield cohort when compared to age > 60 years (88.3% vs. 79.2% respectively, p=0.036).
• Notably, past history of SARS-CoV-2 infection resulted in a significantly greater antibody responder rate compared to SARS-CoV-2 naïve individuals in overall cohort (96.7% vs. 77.2%, p<0.001)
• Multiple logistic regression analysis (to identify the independent predictors for non-responder rate based on development of SARS-CoV-2 Anti-spike antibody) suggests that amongst all the variables analyzed, three variables such as- presence of comorbidities, past history of SARS-CoV-2 infection and vaccine type were independent predictors of antibody response rate.
• No differential antibody responder rate was observed with regard to gender, body mass index (BMI), blood groups, presence of T2DM, dyslipidemia and IHD including its duration and management strategies.
• Very Important findings in regard to Post-vaccination adverse events and post-vaccination SARS-CoV-2 infection emerged. In the overall post-vaccination cohort, the Covishield arm had a higher proportion of patients having any side-effects as compared to Covaxin arm (46.7% vs. 31.2%, p=0.006). Notably, in the propensity-matched cohort, any side-effects post vaccination was also higher in the Covishield compared to the Covaxin arm (50.0 % vs. 30.2%, p=0.008).

CME INDIA Learning Points from COVAT Study (Interim Results)

• While both vaccines elicited immune response, seropositivity rates to anti-spike antibody were significantly higher in Covishield recipient compared to Covaxin after the first dose.
• Past history of SARS-CoV-2 infection had a significantly higher responder rate and median anti-spike antibody titre compared to the SARS-CoV-2 naïve individuals, after the first dose of either of the two vaccines.
• Any adverse side effects post-vaccination was significantly higher in Covishield recipient compared to the Covaxin; however, these adverse events were mild to moderate in nature.
• Whether the differential finding between two vaccines is related to a lesser number of participants in Covaxin arm compared to the Covishield or due to the difference in characteristics of participants or related to differential immunogenic response due to the difference in loading dose of antigen in vaccine – is not exactly known – and need further studies.
• Ongoing COVAT study will further advance knowledge on anti-spike antibody kinetics after the second dose of two vaccines until 6-month post-vaccination.
• Amongst the captured co-morbidities, only history of HTN was associated with a significantly lower response rate compared to those without (65.7% vs. 82.3%, p=0.001), and it was mainly driven by lower responder rate in Covishield arm.
• As this study is not studying the T-cell response, we do not know about the exact protection we get post vaccination.

Reference:

https://www.medrxiv.org/content/10.1101/2021.04.07.21255078v1 Preprint doi: https://doi.org/10.1101/2021.04.07.21255078; this version posted on April 13, 2021

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