Covishield (also marketed as VaxZevria in Europe and UK) is again in the news, with its maker AstraZeneca (AZ) admitting in a UK court that its vaccine can cause thrombosis (blood clot), in rare instances. The British company is facing a lawsuit in the UK for allegedly causing death and serious injury. The company has admitted in court documents that the vaccine “can, in very rare cases, cause TTS (Thrombosis Thrombocytopenia Syndrome)”. During 2020, AZ developed a vaccine against Covid-19, in collaboration with Oxford University and manufactured at the Pune-based Serum Institute of India. This vaccine was a chimpanzee adenovirus-based vaccine, encoding with Spike glycoprotein of SARS-CoV2. There are 15 other vaccines for COVID-19 which are approved or approved for restricted use in emergency in India, several of which are adenovirus-based. Covaxin, another for Covid-19 vaccine developed by Hyderabad-based Bharat Biotech, is based on the inactivated whole virion of SARS-CoV2.
Any medicines, including vaccines, are tested in a small number of patients/humans (these studies are called clinical trials), for confirming that they are safe as well as efficacious, before being approved for human use. However, since the testing is done on a very small set of patients, data is continued to be collected (specifically on any side-effects) after it is approved and used in a larger population. This is called post-marketing surveillance or pharmacovigilance, and is a requirement from regulatory medicine authorities worldwide.
Covishield, like any other medicine/vaccine, has adverse drug reactions (side-effects, in layman’s terminology), such as fatigue, pain at the site, fever, muscular pain, headache etc. However, in some of the patients who have received adenovirus-based vaccine, a rare but life-threatening adverse effect has presented, of severe thrombosis (blood clots) with thromobocytopenia, which was later termed as “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” or “vaccine-induced immune thrombotic thrombocytopenia (VITT).
VITT is a condition in which there is thrombosis (blood clots) in various sites in the body (which can be in the brain as well as other parts), along with low platelet counts. This is characterised usually by:
Severe headache
Leg pain/swelling
Abdominal pain
Shortness of breath
Low platelet counts
Bruising/bleeding/petechiae (small spots of bleeding under the skin)
It must be noted that VITT usually develops after four to 42 days of vaccine administration and, as mentioned before, occurrence of this side-effect is very rare (around 1 in 100,000). This vaccine-induced blood clotting (VITT), though life-threatening, has treatment options recommended by the American Society of Hematology (ASH) and World Health Organization (WHO).
The European Medicine Agency (EMA) had received several reports of thrombosis (approximately 30 case for five million doses), as early as March 2021. Similarly, several cases were also reported in the US (however, US has a slightly different adenovirus vaccine by J&J). Following the initial reports, EMA notified on their website that “the vaccine’s benefits continue to outweigh its risks and the vaccine can continue to be administered while investigation of cases of thromboembolic events is ongoing”. Further to this, after the review of “Procedural steps taken and scientific information after the authorisation” of VaxZervia (of AZ), which is published by EMA, it can be clearly seen that based on the information submitted by AZ, patient information (which comes along with the vaccine) was being updated as well, for inclusion of thrombosis-related information as well as recommendation.
In India, the currently approved product insert of Covishield states: “A very rare and serious combination of thrombosis and thrombocytopenia including thrombosis with thrombocytopenia syndrome (TTS), in some cases accompanied by bleeding, has been observed following vaccination with with ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) during post-authorisation use.” There are more than 200 published scientific articles since 2021 on thrombosis with thrombocytopenia. However, at this moment, there is no published /publicly available information on the number of cases reported in India on the Central Drugs Standard Control Organisation’s website. As to why these side-effects are developed is currently not clear, but scientists (including AZ’s technical team) are still postulating on the mechanism of these side-effects. Regardless, medical researchers and regulatory authorities alike believe that despite the risk of TTS and VITT, the risk-benefit ratio for adenovirus-based vaccines (such as Covishield) remains positive. Long-term side-effects and their impact can be significantly managed by early detection and appropriate treatment. Health authorities worldwide have not raised any serious safety concerns and vaccine remains available and approved for human use.
It should be noted that contrary to popular belief and rumour-mongering on social media, this side-effect (blood clotting with low platelet counts) is not something new which was not previously known or which has recently surfaced. Frequency/occurrence of this (based on the currently available data) is very low (currently about 20 cases per million), though it is acknowledged that reporting of such cases from India and other underdeveloped nations is not as much as from the US and Europe, due to differences in pharmacovigilance systems.
While it is proven that Covishield (and similar vaccines) can cause blood clots, based on available data, research and assessment by the regulatory authorities, the benefit of the vaccine outweighs the risk associated with its use. Collection of the data on side-effects and its evaluation and communication by Indian regulators and public health stakeholders (including ICMR and IMA) remains to be seen, while netizens and social media users are going agog, as they often do, with speculation, memes and jokes.
A Ahmed works in the pharmaceutical industry, and writes on health and poetry
