CoviShield™ COVID-19 Vaccine Clinical Trials, Dosage, Indication, Side Effects
AstraZeneca CoviShield™ COVID-19 (AZD1222) (C19VAZ) vaccine is made from the ChAdOx1 virus, a weakened version of a common cold virus (adenovirus). In addition, genetic material has been added to the ChAdOx1 construct, which is used to make proteins from the SARS-CoV-2 coronavirus called Spike glycoprotein (S). Drug regulators in India granted emergency approval for the coronavirus vaccine co-developed by AstraZeneca Plc and the University of Oxford on January 1, 2021. This vaccine is the same formulation as the Vaxzevria vaccine, the Serum Institute of India (SII) version of the ChAdOx1 vaccine.
On February 15, 2021, the World Health Organization (WHO) recommended the SII's COVISHIELD. On March 19, 2021, the WHO confirmed that Covishield has a favorable benefit-risk profile with tremendous potential to prevent infections and reduce deaths worldwide. On April 23, 2021, the Centre for Cellular and Molecular Biology announced that CoviShield might protect people from various SARS-CoV-2 mutations. On June 15, 2021, AstraZeneca announced that the Real-world data from PHE demonstrated two doses of COVID-19 Vaccine AstraZeneca are 92% effective against hospitalization due to the Delta variant and showed no deaths among those vaccinated. In addition, the vaccine also showed high effectiveness against the Alpha variant (B.1.1.7), with an 86% reduction in hospitalizations and no deaths reported. According to a study conducted by India's ICMR-National Institute of Virology in April 2022, Covishield-generated neutralizing antibodies against the Delta variant began to wane after six months.
The NEJM published a Correspondence based on data from Scotland on October 20, 2021, that found the ChAdOx1 nCoV-19 vaccine (CoviShield, AstraZeneca) offered substantial protection against death from COVID-19 caused by the delta variant. In addition, the Oxford-AstraZeneca vaccine was 91% effective in preventing deaths in people who have been double vaccinated but have tested positive for coronavirus in the community. The NEJM published an ORIGINAL ARTICLE on December 16, 2021, concluding the AZD1222 vaccine was safe and efficacious in preventing symptomatic and severe COVID-19 across diverse populations, including older adults in the significant phase 3 clinical trial. In addition, on April 16, 2022, a non-peer-reviewed study demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai, India.
Published by MDPI in the journal Vaccines on December 14, 2022, a study titled "Heterologous Booster Dose with CorbeVax® Following Primary Vaccination with COVISHIELD Enhances Protection against SARS-CoV-2" showed that both homologous (Covishield priming Covishield boosting) and heterologous boosters (Covishield priming Corbevax boosting) induce strong SARS-CoV-2 S1/S2 spike IgG antibody responses. The data shows that more individuals had higher antibody titers in individuals receiving a heterologous booster than a homologous booster. The RBD-specific antibody response was much more significant when Corbevax was administered as a heterologous booster after two doses of Covishield, probably due to the protein nature of the vaccine. The study also demonstrates increased CD4 T lymphocyte responses sustaining up to 90 days and beyond in individuals receiving Corbevax as a heterologous booster.
A non-peer-reviewed study published on January 5, 2023, found Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population. On January 23, 2023, the Lancet Regional Health South East published a study that concluded homologous and heterologous boosting with COVISHIELD or COVAXIN® in COVISHIELD or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD after COVAXIN® prime offers the best immune response among the evaluated combinations. A study published on September 14, 2023, provides detailed evidence on the magnitude and quality of CoviShield and Covaxin vaccine-induced responses in subjects with pre-existing SARS-CoV-2 immunity. On October 16, 2023, a study conducted by doctors of Veer Surendra Sai Institute of Medical Sciences and Research (Vimsar) measured the antibody levels both before and after the booster shot. The results showed the antibody levels significantly increased after the booster shot, with a mean fold increase of more than 30.
India publishes a FAQsQ. Registered Trials listing of the CoviShield - Oxford/AstraZeneca vaccine (AZD1222).
Serum Institute of India (SSI) Pvt. Ltd. is now the world's largest vaccine manufacturer by the number of doses produced and sold globally (more than 1.5 billion doses). Media reported on November 9, 2022, that SSI has supplied over 1.9 billion doses of Covishield vaccines globally. The Poonawalla Bio-Tech Park at Manjari in Pune is a State-of-the-Art facility designed to meet the highest standards set by many regulatory agencies, including the MHRA, the U.S. FDA, Europe, Japan, Australia, etc.
CoviShield Availability
The WHO Listed CoviShield in 2021, and it remains one of the 12 COVID-19 vaccines granted an EUL by the WHO. On April 12, 2023, PTI reported that SII's CEO, Adar Poonawalla, confirmed that Covishield manufacturing had restarted. As of April 2023, about 49 countries in Africa, the Caribbean, and South America have approved CoviSheld. However, the U.S. Food and Drug Administration (FDA) had not authorized the Covishield vaccine since December 2023.
CovoVax™ Vaccine
COVOVAX™ is a SARS-CoV-2 rS Protein recombinant COVID-19 vaccine developed with Novavax Inc. One dose (0.5 mL) contains five micrograms of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M1. Adjuvant Matrix-M1 containing per 0.5 mL dose: Fraction-A (42.5 micrograms) and Fraction-C (7.5 micrograms) of Quillaja saponaria Molina extract. The SARS-CoV-2 recombinant spike protein is produced by recombinant DNA technology using a baculovirus expression system in an insect cell line derived from Sf9 cells of the Spodoptera frugiperda species.
On September 13, 2022, Novavax, Inc., and SII announced that the South African Health Products Regulatory Authority had granted complete product registration with conditions for Novavax's protein-based vaccine, NVX-CoV2373, under the brand name Covovax™. On November 22, 2022, Reuters reported Gavi's spokesperson said Serum Institute had a 300 million dose commitment for Covovax, with options for 750 million more doses if needed.
CoviShield SARS-CoV-2 Variant Sublineages
As of December 2022, the U.S. NIH OpenData Portal reports the SARS-CoV-2 variant impact on COVID-19 vaccine effectiveness. On December 23, 2021, AstraZeneca announced Vaxzevria (ChAdOx1-S [Recombinant]) (Covishield) significantly boosted levels of antibodies against the Omicron SARS-CoV-2 variant (B.1.1.529) following a third dose booster, according to data from a new laboratory study. The neutralizing antibody levels against Omicron following a third dose boost of Vaxzevria were similar to levels achieved after two doses against the Delta variant. Data from a non-peer-reviewed laboratory study published on December 20, 2021, supported AstraZeneca's Vaxzevria's effect against Omicron, with individuals vaccinated with two doses of Vaxzevria retaining neutralizing activity against Omicron. However, a decrease was seen compared to the original strain.
U.K.'s Health Security Agency (UKHSA) confirmed on December 10, 2021, that two doses of the CoviShield vaccine were less effective at stopping the new variant than Delta. However, a third dose protected around 75% of people in the small study.
CoviShield History
The WHO granted Emergency Use Listing to the AstraZeneca - Oxford COVID-19 vaccine 'COVISHIELD' ChAdOx1-S [recombinant] manufactured by Serum Institute of India on February 15, 2021. WHO's EUL assesses the quality, safety, and efficacy of COVID-19 vaccines. It is a prerequisite for COVAX Facility vaccine supply, enabling countries to expedite their regulatory approval to import and administer COVID-19 vaccines. As of mid-July 2022, the Times of India reported that 200 crore vaccines had been distributed 18 months after the vaccinations began on January 16, 2021.
CoviShield is Listed by the Caribbean Regulatory System, the WHO, the Africa Regulatory Taskforce, and Europe.
Covishield Dosing
Based on the recommendations by the National Expert Group on Vaccine Administration for COVID-19, the dosing schedule of the Covishield vaccine under India's National Covid-19 Vaccination Strategy is to administer the second dose at 12-16 week intervals (i.e., after 84 days) after administering the first dose.
Covishield Women
Pregnant women "can and should" be vaccinated against COVID-19, the India Union Health Ministry announced. "The Health Ministry has guidelines for giving the vaccine to pregnant women. Therefore, vaccination is useful for them and should be given," said Dr. Balram Bhargava, Director-General of the Indian Council for Medical Research, on June 25, 2021. In September 2022, the U.S. NIH reported a link between COVID-19 vaccination and a temporary increase in menstrual cycle length.
Covishield Children
The Lancet published the findings from a peer-reviewed study on June 11, 2022, 'ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6–17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial.'
CoviShield Side Effects
On May 3, 2022, the journal BMC Infectious Diseases published - Determinants of Associated Events following AZD1222 (Covishield) vaccination in a high-risk population in Nepal. After the second dose, only 31.2% (95% CI 27.2–35.2) reported adverse events, the overwhelming majority of which were mild (95.7%) and required a lower frequency of medication (7.5% vs. 26.0%).
A rare new type of adverse event called Thrombosis with Thrombocytopenia Syndrome, involving unusual and severe blood clotting events associated with low platelet counts, has been reported after vaccination with the COVID-19 Vaccine Covishield. The Annual of Internation Medicine published Original Research on February 1, 2022, that concluded this exploratory retrospective cohort study among frontline personnel in Denmark found the receipt of the AZD1222 (CoviShield) vaccine was associated with a small excess risk for deep venous thrombosis. In addition, on January 20, 2022, the EMA published safety updates for the AstraZeneca vaccine, which reported no new safety signals were identified, and no conclusions on any ongoing signals were reached. Therefore, EMA confirms that the benefits of CoviShield / Vaxzevria continue to outweigh its risks, given the risk of COVID-19 illness and related complications, including hospitalization and death.
On May 7, 2022, there were two case reports: Superficial venous thrombosis, a possible consequence of the ChAdOx1 nCoV-19 vaccine. However, the vaccine's benefits in breaking the chain of COVID-19 spread are certainly more significant than the risk of thromboses.
CoviShield Ingredients
CoviShield ingredients can be found on the University of Oxford website. Updated FAQs are also posted at this link.
CoviShield Vaccine Price
According to local media in India, Prakash Kumar Singh, Director of Government and Regulatory Affairs at SSI, offered the Health Ministry Covisheld doses worth Rs 410 crore free of cost on December 28, 2022.
CoviShield Travel
The European Commission proposed extending the E.U. Digital COVID Certificate until June 30, 2023. CoviShield is included in various country authorizations.
Covisheld and BCG Vaccination
Original Research published on October 4, 2022: Evidence for the heterologous benefits of prior BCG vaccination on COVISHIELD™ vaccine-induced immune responses in SARS-CoV-2, seronegative young Indian adults. BCG revaccination enhances the magnitude of COVISHIELD-induced spike-specific immune responses.
CoviShield News
December 23, 2022 - Local media reported Dr. D Nageshwar Reddy, Chairman, AIG Hospitals stated, "We knew from our previous studies that mixed vaccines produce better immune response; therefore when the Govt approved Corbevax to be given as a heterologous booster to individuals already vaccinated with COVISHEILD, we aimed to determine how a different vaccine platform (protein-based) will impact the immune response, especially in context of the Omicron variant."
June 30, 2022—Taylor Francis Online published a Review: Expert review on global real-world vaccine effectiveness against SARS-CoV-2: Protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of Asian and relevant international data and insights from SEA experts.
March 22, 2022 - Wiley Online published Original Research: Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals. Conclusions - Both dosing schedules resulted in high antibody and T-cell responses post-vaccination. However, those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured six weeks post the second dose compared to 12 weeks post the second dose.
January 4, 2022 - The U.S. FDA confirmed it found an additional three lots of AstraZeneca COVID-19 vaccine drug substance manufactured at the Emergent facility in Baltimore, Maryland, to be acceptable for use for potential export.
November 25, 2021 - The Lancet published the results from a late-stage study - two doses of ChAdOx1 were 63·1% effective against SARS-CoV-2 infection, caused mainly by the delta variant, and prevented moderate-to-severe COVID-19 in 81·5% of cases.
November 12, 2021 - Saudi Arabia recognized Covishield as an approved Covid vaccine for entry into the country.
July 28, 2021 - Covishield vaccine gives 93% protection against COVID-19 and reduces the mortality rate by 98%, according to a study by the Armed Forces Medical College based in India.
April 16, 2021 - The WHO published a statement: 'Global Advisory Committee on Vaccine Safety review of the latest evidence of rare adverse blood coagulation events with AstraZeneca COVID-19 Vaccine (Vaxzevria and Covishield).
The India Ministry of Health and Family Welfare announced on March 22, 2021, 'Given the emerging scientific evidence, the interval between two doses of COVISHIELD has been revisited by National Technical Advisory Group on Immunization and subsequently by National Expert Group on Vaccine Administration for COVID-19 in its 20th meeting. During this meeting, the recommendation has been revised to provide a 2nd dose of COVISHIELD at 4-8 weeks intervals after the 1st dose instead of an earlier practiced interval of 4-6 weeks.'
CoviShield Clinical Trials
November 12, 2020 - The Serum Institute of India and Indian Council of Medical Research announce the completion of enrollment for phase 3 clinical trials for COVISHIELD in India.
November 21, 2021 - The Lancet reported: A phase 2/3, participant-blind, observer-blind, randomized, controlled study to assess the safety and immunogenicity of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine) in adults in India.
Recent Covishield clinical trials are searchable at Investigating a Vaccine Against COVID-19 - Full Text View.
