Why the recommended time gap between two covishield vaccine doses is 90 days and above?

Covishield: effectiveness of a single dose and recommended gap between two doses: results of scientific clinical trial

• The 'exploratory research' was conducted between 23.April.2020-6.Dec.2020 by University of Oxford, UK [1-2].  

• Two single blind trials in UK, one in Brazil and one double blind trial in South Africa were conducted with individuals 18 years and above who were randomly selected to receive two standard doses of Covishiled or a placebo[3-6].

• Total 17,178 individuals were part of the study and among them 8,597 received covishield vaccine and 8,581 received placebo. 

Fig.1: Covishield vaccine made by Serum Institute of India, Pune, India

• Effectiveness of the vaccine after its administration was estimated with positive COVID test i.e. nucleic acid amplification test (NAAT) and at least one of the symptoms like fever (≥37·8°C), or cough or shortness of breath, or complete loss of smell (anosmia) or complete loss of taste (ageusia). 

• No one had any evidence of previous SARS-CoV-2 infection from NAAT swabs. 

• A single standard dose of covishield had an efficacy of 76·0% against symptomatic COVID-19 in the first 90 days after vaccination, with no significant decrease of protection during this period (Black line in Fig.2 and Table.1). 

• Vaccine efficacy 81·3% at ≥12 weeks vs 55·1% at <6 weeks gap between two standard doses (Red line in Fig.2 & Table.1). 

• Data quoted by the researchers with 95% confidence interval, which means that, the sample method is representative of the population with 95% certainty.

Fig.2.: Effectiveness of Covishield vaccine after single dose (black line) and as a function of gap between two doses (red line) [1]. 

Table.1: Vaccine effectiveness data [1]. Fig.2 was plotted with colour shaded data. 

• A second dose of covishield induces increased "neutralising antibody" which is probably necessary for long-lasting protection. 

• Increased neutralising antibody has been seen with influenza, Ebola, and  malaria vaccines.

• This clinical trial has scientifically proven that 1^st dose of covishield vaccine is effective upto 90 days and 2^nd dose is more effective after 90 days (approx). 

• Similar study is yet to be published for India's indigenous COVID19 vaccine Covaxin, which is developed by Bharat Biotech, Hyderabad. We shall review it once such data is available to public.
  

Reference and Footnotes

[1] Voysey, Merryn, et al. "Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials." The Lancet 397.10277 (2021): 881-891. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext Published:February 19, 2021 DOI:https://doi.org/10.1016/S0140-6736(21)00432-3

[2] The published study is an exploratory research, which is used to investigate problems which are not clearly defined but needs better understanding without providing a conclusive result. 

[3] As per clinical trials protocols, bias towards desired result needs to be minimised and blindfolded experiment, placebo etc are few of them. In single-blind study, only the patients are unaware if they are receiving the real treatment or placebo. In a double-blind study, both patients and doctors are unaware. In a triple-blind study, the patients, doctors and the data scientists are unaware of the fact. 

[4] One standard dose of Covishiled contains 5 × 10¹⁰ viral particles in 0.5 mL volume. 

[5] ChAdOx1 nCoV-19, Covishield, Oxford vaccine, Astrazeneca vaccine are the same vaccine, known by different names in different countries. 

[6] A placebo is used to compare its effects with those of a real drug and it is used to study, patient's psychological response. Sometimes, patients condition becomes better with the use of placebo drug. Examples are, similar looking medicine but without actual chemical. 

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