OFFICIAL REPORTS ON PHARMACOVIGILANCE PROGRAMS - 4 October 2021

CANADA 

As of 24 September 2021, 38,472,075 doses of the COVID-19 vaccine of Pfizer-BioNTech, 13,592,652 doses of the Moderna vaccine, and 2,787,374 doses of the AstraZeneca/Covishield vaccine (AstraZeneca vaccine manufactured by the Serum Institute of India) had been administered. 

A total of 17,124 individual reports of one or more adverse events (0.031% of doses administered) were received. Of these, 4,505 reports involved serious events (0.008% of doses administered).  

There were 46,000 reports of adverse events following immunization (AEFI), of which 17,124 involved one or more events. The most frequently reported adverse events were injection-site reactions, paresthesia, headache, pruritis, dyspnia, fatigue, nausea, etc.

An analysis of 808 of the 812 cases of myocarditis/pericarditis, with indication of the vaccine administered, is shown below:

Source: Public Health Agency of Canada. Canadian COVID-19 vaccination safety report. Ottawa: Public Health Agency of Canada; 4 October 2021. https://health-infobase.canada.ca/covid-19/vaccine-safety/. Data reproduced by PAHO/WHO.

CARIBBEAN PUBLIC HEALTH AGENCY (CARPHA)

The Caribbean Regulatory System (CRS), through the Caribbean Public Health Agency (CARPHA), in the latest update published on its website, indicates that as of 24 September 2021 approximately 4,507,347 doses of COVID19 vaccines, included in the WHO Emergency Use Listing (EUL), had been administered  in the CARPHA member countries (Anguilla, Antigua and Barbuda, Aruba, Bahamas, Barbados, Belize, Bermuda, Bonaire, St. Eustatius,

Saba, British Virgin Islands, Cayman Islands, Curacao, Dominica, Grenada, Guyana, Haiti, Jamaica, Montserrat, Saint Kitts and Nevis, Saint Lucia, Saint Martin, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, and Turks and Caicos Islands). As of the same date, 38 reports of AEFI had been received through an online reporting form since August 2021, the date on which the form was instituted. Of  these reported cases, 13 were serious, including one death.

These reports are being verified and/or investigated by local authorities.

Source: CARPHA_COVID-19_ Vaccine_Update_038_September_27, 2021.pdf

COVID-19 vaccination for pregnant women, and pregnancy outcomes 

On 1 October, one of the largest ever observational cohort studies of pregnant women was published. Its objective was to study the association between prenatal Pfizer-BioNTech COVID-19 vaccination, pregnancy course, and outcomes. A retrospective cohort study was performed, including all women who delivered between January and June 2021 at Soroka University Medical Center, in Israel. Excluded were women diagnosed with COVID-19 in the past, multiple gestations, or unknown vaccination status. Pregnancy, delivery, and newborn complications were compared between women who had received one- or two-dose vaccines during pregnancy and unvaccinated women. A total of 4,399 women participated in this study, of whom 913 (20.8%) were vaccinated during pregnancy. All vaccinations occurred during the second or third trimester. As compared to the unvaccinated women, the vaccinated women were older, more likely to conceive following fertility treatments and to have sufficient prenatal care, and were of higher socioeconomic position. In both crude and multivariable analyses, no differences were found between groups, in terms of pregnancy, delivery, and newborn complications, including gestational age at delivery, incidence of small for gestational age, and newborn respiratory complications. The authors conclude that prenatal maternal COVID-19 vaccination with the Pfizer-BioNTech vaccine has no adverse effects on pregnancy course and outcomes. 

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421099/pdf/main.pdf

Declining mortality from cerebral venous sinus thrombosis with thrombocytopenia (CVST) after SARS-CoV-2 vaccination

On 18 September, an observational study was published evaluating whether the mortality of patients with cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) has decreased over time.

The EudraVigilance database, of the European Medicines Agency, was used to identify cases of CVST with concomitant thrombocytopenia that occurred within 28 days of vaccination against SARS-CoV-2. Vaccines were grouped based on vaccine type (adenoviral or mRNA). Cases with CVST onset up to 28 March were compared with cases after 28 March 2021 – the day when the 

thrombocytopenia were identified, of which 266 (99%) occurred after adenoviral vector SARS-CoV-2 vaccination (ChAdOx1 nCoV-19, n = 243; Ad26.COV2.S, n = 23). The reported mortality among adenoviral cases with onset up to 28 March 2021 was 47/99 (47%, 95% CI 37%–58%), compared with 36/167 (22%, 95% CI 16%– 29%) in cases with onset after 28 March (p = <0.001). None of the four cases of CVST with thrombocytopenia that occurred following mRNA vaccination died. The authors conclude that the reported mortality of CVST with thrombocytopenia following vaccination with adenoviral vector-based SARS-CoV-2 vaccines has significantly decreased over time, which may indicate a beneficial effect of earlier recognition and/or improved treatment on outcome after VIIT. 

Source: https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.15113

Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicenter cohort study

On 25 September, a multicenter cohort study of cerebral venous thrombosis following COVID-19 vaccination, perhaps the largest such study to date, was published. The authors were able, for the first time, to make a direct comparison between 70 patients with VIIT-associated cerebral venous thrombosis and 25 patients who developed cerebral venous thrombosis without evidence of VITT following vaccination, as well as with historical data from a large cohort of patients with cerebral venous thrombosis. The results show, for what appears to be the first time, that when compared to patients without VITT, patients with VITT-associated cerebral venous thrombosis were younger, had fewer risk factors for venous thrombosis, and were more likely to have received the ChAdOx1 vaccine. The group with VITT-associated CVT had more extensive venous thrombosis, and higher rates of thrombosed veins or sinuses. Compared with non-VITT patients, those with VITT-associated cerebral venous thrombosis had more extensive venous thrombosis and higher rates of multiple infarcts, multiple intracerebral hemorrhages, and extracranial thrombosis. Their outcomes, at the end of hospital admission, were worse, with higher rates of death and dependency.  Although the treatment response of patients with VITT-associated cerebral venous thrombosis is difficult to assess in a purely observational study, nonheparin anticoagulants and intravenous immune globulin were associated with better outcomes. The initial criteria for VITT, based on low platelet count and high D-dimers, appeared to overlook two patients who had typical characteristics for this condition, leading the authors to suggest new, more appropriate diagnostic criteria.

VITT is specifically associated with adenovirus vector COVID-19 vaccines. Urgent work is needed to determine the trigger for this reaction, in hopes that future vaccines can be designed to prevent it. Physicians should be aware of the clinical, laboratory, and radiological markers of this condition, since without timely treatment the prognosis is poor. 

Source: Perry RJ, Tamborska A, Singh B et al. Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicenter cohort study. (2021) The Lancet, 398 (10306), 1147–1156. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01608-1/fulltext

Myocarditis and pericarditis after vaccination for COVID-19

On 4 August, an observational study was published that included forty hospitals in Washington, Oregon, Montana, and Los Angeles County, California, that were part of the Providence health care system in the United States, all of which used the same electronic medical record (EMR) system. The aim of the study was to identify vaccinated patients who were seen in the emergency room and were diagnosed with myocarditis, myopericarditis, or pericarditis. All patients with documented COVID-19 vaccinations administered inside the system or recorded in state registries at any time through 25 May 2021, a total of 2,000,287 people, were identified. Vaccinated patients who subsequently had emergency department or inpatient encounters, with diagnoses of myocarditis/myopericarditis (20 cases) or pericarditis (37 cases), were ascertained from EMRs. 

Monthly baseline rates of first-time hospital diagnoses between January 2019 and January 2021 (pre-vaccine period) and February through May 2021 (vaccine period) were compared. The mean monthly number of cases of myocarditis or myopericarditis during the pre-vaccine period was 16.9 (95% CI, 15.3-18.6) vs 27.3 (95% CI, 22.4-32.9) during the vaccine period (p <.001). The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-

51.9) and 78.8 (95% CI, 70.3-87.9), respectively (p < .001).

Two distinct self-limited syndromes, myocarditis and pericarditis, were observed after COVID-19 vaccination. Myocarditis developed rapidly in younger patients, mostly after the second vaccination. Pericarditis affected older patients later, after either the first or second dose.

Some vaccines are associated with myocarditis, including mRNA vaccines, and the Centers for Disease Control and Prevention (CDC) recently reported a possible association between COVID-19 mRNA vaccines and myocarditis, primarily in younger male individuals within a few days after the second vaccination, at an incidence of about 4.8 cases per million. This study shows a similar pattern, although at higher incidence, suggesting underreporting of vaccine-related adverse events. Additionally, pericarditis may be more common than myocarditis among older patients.

Study limitations include cases missed in outside care settings, and missed diagnoses of myocarditis or pericarditis (which would underestimate the incidence), as well as inaccurate EMR vaccination information. Temporal association does not prove causation, although the short span between vaccination and myocarditis onset, and the elevated incidence of myocarditis and pericarditis in the study hospitals, lend support to a possible relationship.

Source: Diaz GA, Parsons GT, Gering SK, et al. Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA.

2021;326(12):1210–1212. doi:10.1001/jama.2021.13443. https://jamanetwork.com/journals/jama/fullarticle/2782900