OFFICIAL REPORTS ON PHARMACOVIGILANCE PROGRAMS - 22 October 2021

CANADA

 As of 15 October 2021, 39,897,633 doses of the Pfizer-BioNTech COVID-19 vaccine, 14,010,806 doses of the Moderna vaccine, and 2,792,104 doses of the AstraZeneca/Covishield vaccine (AstraZeneca vaccine manufactured by the Serum Institute of India) had been administered.

A total of 20,032 individual reports of one or more adverse events following immunization (AEFI) (0.026% of doses administered) were received. Of these reports, 5,161 involved serious adverse events (0.009% of doses administered).  

In all, there were 53,709 reported AEFI, of which 20,032 involved one or more events. The most frequently reported adverse events were non-serious events such as paresthesia, injection-site pain, headache, pruritus, dyspnea, fatigue, urticaria, nausea, etc. 

An analysis of 951 of the 956 cases of myocarditis/pericarditis, with indication of the vaccine administered, is shown below:

Source: Public Health Agency of Canada. Canadian COVID-19 vaccine safety report. Ottawa: Public Health Agency of Canada; October 22, 2021. https://health-infobase.canada.ca/covid-19/vaccine-safety/. Data reproduced by PAHO/WHO.

CHILE

According to Chile's Ministry of Science, Technology, Knowledge, and Innovation, between 24 December 2020 and 14 August 2021, 26,735,775 doses of COVID-19 vaccines were administered in the country: 18,939,998 doses (70.8%) of the CoronaVac vaccine, 6,813,756 doses (25.5%) of the Pfizer-BioNTech vaccine, 472,202 doses (1.8%) of the AstraZeneca vaccine, and 509,819 doses (1.9%) of the Convidencia/CanSino Biologics Inc. vaccine.

During the same period, there were 11,150 reports of AEFI, as described below:

Of the 10,727 reported cases for which the administered vaccine was known, 7,907 (73.7%) were in women and 2,724 (25.4%) in men; in 96 cases, the sex of the individual was unknown (0.9%).

The group registering the highest number of events consisted of adults between the ages of 16 and 39.

Among the most frequently reported clinical manifestations for the three vaccines were: pain at the injection site, headache, fever, malaise, and myalgia.

The following adverse events of special interest were reported for the vaccines indicated below:

Source: National Institute of Health of Chile; 15 October 2021. Available at: https://www.ispch.cl/wpcontent/uploads/2021/10/20211015-Sexto-informe-estad%C3%ADstico-ESAVI-vacunas-COVID_VF.pdf. Data reproduced by PAHO/WHO.

UNITED STATES

• As of the date of this report, two cases of TTS had been reported to VAERS (for the Moderna vaccine) following the administration of more than 388 million doses of mRNA vaccines in the United States. Based on the available information, there does not appear to be an increased risk of TTS following vaccination with mRNA COVID-19 vaccines.
• As of 13 October, more than 15.2 million doses of the J&J/Janssen COVID-19 vaccine had been administered. The Centers for Disease Control and Prevention (CDC) and the Federal Drug Administration (FDA) have identified 47 confirmed reports of people who received this vaccine and subsequently developed TTS. Women under the age of 50 should be alerted to the increased risk of this adverse event, though it is uncommon. This risk has not been observed in relation to the other available COVID-19 vaccines.
• Following administration of more than 15.2 million doses of the J&J/Janssen vaccine, there have been approximately 233 preliminary reports, as of 13 October 2021, of Guillain-Barré syndrome. These reported cases occurred two weeks after the vaccines had been administered, and were mostly in men, many of whom were 50 years old or older.
• As of 13 October, VAERS had received 1,638 reports of myocarditis or pericarditis in people 30 years old or younger who had received a COVID-19 vaccine. Most reported cases involved individuals who had received an mRNA-based vaccine (Pfizer-BioNTech or Moderna), and occurred particularly in male adolescents and young adults.
• Reports of deaths following vaccination with COVID-19 vaccines are rare. In the United States, more than 408 million doses of COVID-19 vaccine were administered between 14 December 2020 and 18 October 2021, during which time VAERS received 8,878 reports of deaths (0.0022%) among people who had received COVID-19 vaccines.

Source: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html.

MEXICO

• On 6 October 2021, Mexico's Secretariat of Health published a report on AEFI that occurred after administration of COVID-19 vaccines. A total of 79,399,446 doses of vaccines were administered in Mexico between 24 December 2020 and 30 September 2021.
• As of 30 September 2021, 29,646 AEFI had been reported; these are disaggregated by vaccine in the following table:

• The highest proportion of serious (59.45%) and non-serious (73.12%) AEFI occurred in women. In terms of the distribution by age group, the non-serious AEFI occurred mostly in the 30- to 39-year-old age group, while serious AEFI occurred mostly in people over 60 years old (38.45%).
• The main signs and symptoms reported for non-serious AEFI were headache, 64.73% (18,784), injection-site pain or tenderness, 46.03% (13,357), and asthenia, 40.37% (11,717); while the most common serious AEFI reported were headache, 45.80% (349), asthenia, 37.80% (288), and dyspnea, 32.28% (246).

Source: https://www.gob.mx/cms/uploads/attachment/file/671870/REPORTE_ESAVI_2021_09.pdf

Publications on potential safety signals identified with the use of COVID-19 vaccines

Cerebral venous sinus thrombosis and other thrombotic events following administration of viral vectorbased COVID-19 vaccines: Systematic review and meta-analysis

On 5 October, a systematic review and meta-analysis of cerebral venous sinus thrombosis and other thrombotic events following administration of COVID-19 viral vector vaccines was published. The objective was to systematically evaluate the scientific literature on the proportion of cases of cerebral venous sinus thrombosis (CVST) among the cases of thrombosis with thrombocytopenia syndrome (TTS), and to evaluate its characteristics and outcomes. A systematic review and meta-analysis of clinical trials, cohort studies, case series, and registry-based studies was conducted, in order to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS; and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic events. Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vectorbased vaccine administration. Twenty-three studies were further included in the quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% CI: 36–66%; P = 61%). TTS was independently associated with a higher likelihood of CVST, when compared to non-TTS patients with thrombotic events after vaccination (OR: 13.8; 95% CI: 2.0-97.3; P = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI: 21–36%) and 38% (95% CI: 27–49%), respectively. Thrombotic complications developed within two weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval: 10 days; 95% CI: 8–12), and affected predominantly women under the age of 45 (69%, 95% CI: 60–77%), even in the absence of pro-thrombotic risk factors.

The authors conclude that approximately half of TTS cases present with CVST, while nearly one-third of TTS patients do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. In addition, the authors urge caution regarding the findings presented, since there is a greater tendency to publish information on cases with severe clinical manifestations.  

Source: Palaiodimou L, Stefanou MI, Katsanos AH, et al. Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis. Neurology. 2021 Oct 5:10.1212/WNL.0000000000012896. doi: 10.1212/WNL.0000000000012896. Preprint Epub. PMID: 34610990. Available at: https://n.neurology.org/content/early/2021/10/05/WNL.0000000000012896.long.

Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study

On 27 September, a cohort study conducted in Israel, with a control group, was published, whose objective was to analyze the presence of Bell's palsy, shingles, Guillain-Barré syndrome (GBS), and other neurological conditions after vaccination against COVID-19 (Pfizer BNT162b2 vaccine). Rates were compared between vaccinated and unvaccinated individuals. Individuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical cohort study, in a health maintenance organization insuring 1.2 million Israeli citizens. Each vaccinated person was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish), and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of Bell's palsy, GBS, herpes zoster, or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review. Of 406,148 individuals vaccinated during the study period, 394,609 (97.2%) were eligible (11,539 were excluded). A total of 233,159 (59.1%) were matched with unvaccinated controls. Mean follow-up was 43 ± 15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR 0.96, CI: 0.54–1.70), one versus zero cases of GBS, 151 versus 141 cases of herpes zoster (RR 1.07, CI: 0.85–1.35), and 605 versus 497 cases of numbness or tingling (RR 1.22, CI: 1.08–1.37), respectively. The authors note that in this study no association was found between vaccination and the clinical presentation of Bell's palsy, herpes-zoster, or GBS. Symptoms of numbness or tingling were more common among vaccinated individuals.  

Source: Shasha D, Bareket R, Sikron FH, et al. Real-world safety data for the Pfizer BNT162b2 SARS-CoV2 vaccine: historical cohort study. Clin Microbiol Infect. 2021 Sep 27:S1198–743X(21)00538–3. doi:

10.1016/j.cmi.2021.09.018. Preprint Epub. PMID: 34592420; PMCID: PMC 8479307. Available at: https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00538-3/fulltext.