Statement of the COVID-19 subcommittee of the WHO Global Advisory Committee on Vaccine Safety (GACVS) on safety signals related to the Johnson &…

As of 18 May 2021, there were163,312,429confirmed casesof COVID-19, including3,386,825deaths, reported to WHO. Vaccination remains a critical tool to help prevent further illness and death and to control the pandemic.

The Johnson & Johnson (J&J)/Janssen vaccine was listed for emergency use by WHO on 12 March 2021. The vaccine has been authorized for use in Europe, the United States and other countries, with the widest experience to date in the United States, where more than 8 million doses of the J&J vaccine had been administered as of 7 May.

The GACVS COVID-19 subcommittee met virtually on 11 May 2021 to review available information and data on thromboembolic events (blood clots) and thrombocytopenia (low platelets) after vaccination with the adenoviral vectored J&J vaccine. This condition is referred to as thrombosis with thrombocytopenia syndrome (TTS). Current evidence suggests a plausible causal association between the J&J COVID-19 vaccine and TTS. Clinically, the features of TTS following vaccination with this vaccine appear similar to those observed following another adenoviral vectored vaccine, the AstraZeneca COVID-19 vaccine. TTS does not appear to be associated with the mRNA COVID-19 vaccines. The exact mechanism by which this rare condition occurs is not fully understood. (1) To date, the only possible risks factors identified are age and gender (with more cases reported in women).

The subcommittee reviewed detailed surveillance data from the United States, which included stimulated passive surveillance and a small active surveillance cohort.

Based on a careful scientific review of the available information, the subcommittee came to the following conclusions and recommendations:

- The benefits of the J&J COVID-19 vaccine continue to outweigh the risks of TTS. As the only single dose COVID-19 vaccine approved for use to date, the vaccine may be an important tool for accessing difficult-to-reach populations, thus playing a key role in preventing infections and reducing deaths across the world.

- Very rare thromboembolic events, in combination with thrombocytopenia, have been reported following vaccination with the J&J vaccine in the United States. As of 7 May 2021, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) had reviewed 28 reports of TTS out of a total of more than 8 million vaccinations; TTS was reported in persons between 18-59 years of age (median age of 40 years) and occurring after 3-15 days (a median of 9 days).(2) To date, the US FDA and CDC have not identified any cases of TTS after use of over 240 million doses of mRNA vaccines.

- Reports of TTS following vaccination with the J&J vaccine have a similar clinical picture to those reported following vaccination with the AstraZeneca COVID-19 vaccine. On 16 April 2021 the GACVS COVID-19 subcommittee issued an updated statement on blood coagulation events and the AstraZeneca COVID-19 vaccine. (3)

- Although most cases of TTS have typically involved thrombosis in unusual locations, including cerebral venous sinuses, portal vein, splenic vein and other rare venous and arterial thrombosis, cases including thrombosis in more common locations, such as deep vein thrombosis and pulmonary embolism, have been identified in the United States.

- When setting their immunization policies, the risk of TTS from use of the J&J vaccine should be assessed against the benefits. Countries should perform such a benefit-risk analysis taking into account local epidemiology (including incidence and mortality from COVID-19 disease), age groups targeted for vaccination, and the availability of alternative vaccines.

- Adequate education should be provided to health-care professionals and persons being vaccinated to recognize the signs and symptoms of all serious adverse events after vaccinations with all COVID-19 vaccines, so that people may seek and receive prompt and relevant medical care and treatment.Early identification of TTS is important in order to initiate appropriate treatment.

- Clinicians should be alert to any new, severe, persistent headaches or other significant symptoms, such as severe abdominal pain and shortness of breath, with an onset between 4 to 20 days after adenovirus vectored COVID-19 vaccination. At a minimum, countries should encourage clinicians to measure platelet levels and conduct appropriate investigation of thrombosis. Clinicians should also be aware that although heparin is generally used to treat blood clots, administration of heparin in TTS may be dangerous and alternative treatments such as immunoglobulins and non-heparin anticoagulants should be considered.

- The GACVS subcommittee recommends that countries continue to monitor the safety of all COVID-19 vaccines and promote reporting of suspected adverse events. In particular, any blood clots following receipt of any COVID-19 vaccine should be reported.

- The GACVS subcommittee acknowledges that TTS has occurred with two adenoviral-vectored vaccines. Ongoing assessment for and review of TTS cases, as well as related research, should include all vaccines using adenoviral vector platforms.

The GACVS COVID-19 subcommittee will continue to review the safety data from all COVID-19 vaccines and update any advice as necessary. Open, transparent, and evidence-based communication about the potential benefits and risks to recipients and the community is essential to maintain trust. WHO is carefully monitoring the rollout of all COVID-19 vaccines and will continue to work closely with countries to manage potential risks, and to use science and data to drive the response and update recommendations.

The WHO COVID-19 vaccine safety surveillance manual provides guidance to countries on the safety monitoring and adverse events data sharing for the new COVID-19 vaccines, and can be accessedhere.

(1) Updated recommendations from the US Advisory Committee on Immunization Practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients United States, April 2021: https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e4.htm#contribAff

(2) Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination US Advisory Committee on Immunization Practices (ACIP), 12 May 2021: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf.

(3) Global Advisory Committee on Vaccine Safety (GACVS) review of latest evidence of rare adverse blood coagulation events with AstraZeneca COVID-19 Vaccine (Vaxzevria and Covishield) 16 April 2021: (https://www.who.int/news/item/16-04-2021-global-advisory-committee-on-vaccine-safety-(gacvs)-review-of-latest-evidence-of-rare-adverse-blood-coagulation-events-with-astrazeneca-covid-19-vaccine-(vaxzevria-and-covishield.

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Statement of the COVID-19 subcommittee of the WHO Global Advisory Committee on Vaccine Safety (GACVS) on safety signals related to the Johnson &...