OFFICIAL REPORTS ON PHARMACOVIGILANCE PROGRAMS - 20 December 2021
ARGENTINA (Special report on vaccine safety surveillance in children and adolescents)
- From 28 July 2021 when the adolescent vaccination campaign began, through 12 October 2021 when the vaccination campaign for 3- to 11-year-olds started, and until 31 October 2021, a total of 4,728,885 doses of COVID-19 vaccines were administered in this population group.
- Among the 2,796,720 doses of vaccine administered to adolescents, there were 484 reports of AEFI (17.3 reports per 100,000 doses administered); and among the 1,932,165 doses of vaccine administered to children ages 3 to 11, 153 AEFI were reported (7.9 reports per 100,000 doses administered). For children under the age of 11, the Sinopharm vaccine was used.
- The rate of reports of serious AEFI was 1.2 per 100,000 doses administered for the Sinopharm vaccine, 2.7/100,000 for the Moderna vaccine, and 1.1/100,000 for the Pfizer vaccine.
- The most common adverse events reported for the Sinopharm vaccine were mild and moderate allergic reactions, local reactions without fever, and flu-like symptoms. For the Moderna vaccine, the most common events reported were local reactions without fever, and flu-like symptoms followed by one or more of the following: headache, myalgia, arthralgia, asthenia, and chills. For the Pfizer vaccine, the most frequent adverse events reported were local reactions without fever, followed by one or more of the following: headache, myalgia, arthralgia, asthenia, and chills.
- One reported case of myocarditis following vaccination with the Pfizer vaccine, from which the patient recovered fully, is currently under investigation.
Source: Argentina Ministry of Health. Special report on vaccine safety surveillance in children and adolescents. Argentina, November 2021, available at: https://www.argentina.gob.ar/coronavirus/vacuna/equipos-salud/informesseguridad
BRAZIL (State of Santa Catarina)
- Between 18 January and 30 September 2021, 8,790,520 doses of COVID-19 vaccines were administered in the state of Santa Catarina, consisting of 3,852,286 doses of the AstraZeneca vaccine, 2,397,194 doses of Sinovac/Butantan, 2,284,348 doses of Pfizer-BioNTech, and 256,692 doses of the Janssen vaccine.
- In the same period, there were 10,251 reports of AEFI, representing 0.1% of total doses administered. According to the classification of severity, 9,638 (94%) were non-serious events and 613 (6%) were serious events. Of total events reported, 6,373 were associated with the AstraZeneca/Fiocruz vaccine, 2,528 with the Sinovac/Butantan vaccine, 1,093 with the Pfizer vaccine, and 257 with the Janssen vaccine.
- Most non-serious events involved symptoms such as fever, myalgia, injection-site pain, redness, and edema.
- A total of 242 suspected AEFI-related deaths that occurred within 30 days following vaccination were identified. Of these, the majority (75.2%) occurred in the over-65-year-old population; 227 of the deaths (93.8%) were determined to have no causal relation to the vaccine, two (0.8%) were considered to be causally related to COVID19 vaccines, and 13 (5.4%) are still under investigation.
- The two deaths that were determined to be causally related to the vaccine were associated with the AstraZeneca vaccine, and were classified as thrombosis with thrombocytopenia syndrome (TTS).
Source: Secretary of State of Santa Catarina, Brazil. Boletim de Monitoramento de Eventos Adversos Pós-Vacinação contra a Covid-19 em Santa Catarina. Published 10 November 2021. Available at: https://www.saude.sc.gov.br/index.php/noticias-geral/13079-nota-secretaria-de-estado-da-saude-divulga-boletim-demonitoramento-de-eventos-adversos-pos-vacinacao-contra-a-covid-19-em-santa-catarina
- As of 26 November 2021, 42,033,351 doses of the Pfizer-BioNTech COVID-19 vaccine, 14,709,597 doses of the Moderna vaccine, and 2,798,295 doses of the AstraZeneca/Covishield vaccine (AstraZeneca vaccine manufactured by the Serum Institute of India) had been administered.
- There were 27,798 individual reports of one or more AEFI (0.046% of doses administered). Of these, 6,492 reports involved serious events (0.011% of doses administered).
- Considering all reports, there were 72,292 reported adverse events following immunization (AEFI), with 27,798 reports involving one or more events. The majority of non-serious adverse events consisted of paresthesia, injection-site pain, headache, pruritis, dyspnea, fatigue, urticaria, nausea, etc.
Source: Public Health Agency of Canada. Canadian COVID-19 vaccine safety report. Source: Public Health Agency of Canada; 3 December 2021. Available at: https://health-infobase.canada.ca/covid-19/vaccine-safety/. Data reproduced by PAHO/WHO.
- Vaccination against COVID-19 began in Mexico on 24 December 2020, and as of 29 October 2021, 81,842,426 doses of vaccines had been administered.
- As of 29 October 2021, 31,095 AEFI had been reported by the states’ health services; of these, 97.38% (30,279) were non-serious events and 2.62% (816) were serious events.
- The highest proportion of AEFI, both serious (59.80%) and non-serious (72.50%), occurred in women. The nonserious AEFI occurred primarily in the 30- to 39-year-old age group, while the serious AEFI were mostly in the over-60-year-old age group.
- The most frequently reported non-serious AEFI signs and symptoms were headache, 64.78% (19,616), pain or tenderness at the injection site, 45.71% (13,841), and myalgia, 40.11% (12,145); while the most common serious AEFI were headache, 46.32% (378), asthenia and fatigue, 37.87% (309), and dyspnea, 31.50% (257).
Source: Reporte ESAVI COVID-19 octubre 2021, Dirección de Vigilancia Epidemiológica de Enfermedades Transmisibles. Mexico City. Available at:
- According to the 37th AEFI surveillance report of Paraguay’s Ministry of Health, 6,060,060 doses of COVID-19 vaccines were administered to 3,344,594 people between 22 February and 26 November.
- In that same period, a total of 2,534 AEFI were reported, representing 0.04% of doses administered. A total of 413 reported cases were considered serious, representing 0.007% of doses administered.
- Among reported AEFI, 71.6% (1,815) occurred in women; 68.4% (1,734) were in the 25- to 49-year-old age group.
- Among the reported AEFI, 48.2% (1,221) were in people who received the AstraZeneca vaccine, 14.7% (372) the Sputnik V vaccine, 17.3% (437) the Pfizer/BioNTech vaccine, 7.2% (182) the CoronaVac vaccine, 6.2% (157) the Covaxin vaccine, 4.5% (113) the Moderna vaccine, and 2.1% (52) the Sinopharm vaccine.
Source: 37º Boletín informativo – Vigilancia de ESAVI relacionada a la vacunación contra COVID-19, 26 de noviembre de 2021. Available at: https://pai.mspbs.gov.py/esavis-2021/.
Consolidated reports of adverse events, by vaccine, in countries of the Region of the Americas, December 2021
As of 10 December 2021, 1.378.223.759 doses of COVID-19 vaccines had been administered in the Region of the Americas. The following table presents information provided by the countries regarding number of doses of vaccines administered, by manufacturer and number of associated AEFI:
Consolidated reports of adverse events, by vaccine, in countries of the Region of the Americas, December 2021
Source: Doses obtained from the Dashboard of COVID-19 Vaccination in the Americas.
(https://ais.paho.org/imm/IM_DosisAdmin-Vacunacion.asp. Accessed 10 December 2021.)
- Cases: VigiBase data as of 8 December 2021 and public sources from the countries (Argentina epidemiological bulletin, 31 August; Brazil, as of 25 October, from the epidemiological bulletin, not including the state of São Paulo; Canada country website, 3 December 2021; Colombia, doses per vaccine reported by the country; Mexico, data as of 29 October 2021).
- Countries using the indicated vaccines (countries included in the data presented in the table are in bold):
AstraZeneca: Anguilla, Antigua and Barbuda, Argentina, Bahamas, Barbados, Belize, Bolivia, Brazil, Canada, Chile, Colombia, Costa Rica, Dominica, Dominican Republic, Ecuador, El Salvador, Grenada, Guadalupe, Guatemala, Guyana, Honduras, Jamaica, Montserrat, Mexico, Nicaragua, Panama, Paraguay, Peru, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Virgin Islands, Trinidad and Tobago, and Uruguay.
Bharat Biotech: Paraguay
CanSino: Chile, Mexico
Gamaleya: Argentina, Bolivia, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Saint Vincent and the Grenadines, Venezuela
Janssen: Bolivia, Brazil, Colombia, Haiti, Mexico, USA
Moderna: Argentina, Canada, Colombia, Guadeloupe, Guatemala, Haiti, Honduras, Mexico, Panama, Paraguay, USA
Publications on potential signs of problems with the safety of COVID-19 vaccines
Myocarditis following administration of COVID-19 mRNA vaccines: A case series and incidence rate determination
A cohort study was published on 3 November, its purpose was to analyze the incidence rate of myocarditis and pericarditis in the vaccinated population compared to the incidence rate in the general population. A series of retrospective cases was conducted using the COVID-19 vaccine registry of the Mayo Clinic in the United States. The myocarditis incidence rate and temporal relation to the COVID-19 mRNA vaccine were calculated, compared to the occurrence of myocarditis in a comparable population between 2016 and 2020. Clinical characteristics and outcomes of affected patients were collected. While 21 people were identified, only 7 patients ultimately met the inclusion criteria for vaccine-associated myocarditis. The overall incidence rate ratio (IRR) of COVID-19-related myocarditis was 4.18 (95% CI 1.63, 8.98), which was solely attributable to an increase in IRR among adult men (IRR 6.69, 95% CI 2.35, 15.52) compared to women (IRR 1.41, 95% CI 0.03, 8.45). All cases occurred within two weeks of administration of one dose of a COVID-19 mRNA vaccine, and most occurred within 3 days (range 1–13 days) following the second dose (6/7 patients, 86%). Overall, cases were mild, and all patients survived. The authors conclude that myocarditis is a rare adverse event associated with COVID-19 mRNA vaccines, and that its incidence rate in adult men is significantly higher than in the base population. At present, recurrence of myocarditis following subsequent doses of mRNA vaccines is unknown.
Source: Perez Y, Levy ER, Joshi AY, et al. Myocarditis Following COVID-19 mRNA Vaccine: A Case Series and Incidence Rate Determination. Clin Infect Dis. 3 November 2021 Nov 3;ciab926. doi: 10.1093/cid/ciab926. Online ahead of print, available at: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab926/6420408
A systematic review of cases of central nervous system (CNS) demyelination following COVID-19 vaccination
A systematic review was published on 9 November with the aim of reviewing published cases of CNS demyelination associated with COVID-19 vaccination. The review was conducted in the PubMed, SCOPUS, EMBASE, Google Scholar, Ovid, and medRxiv databases, as of 30 September 2021, of published articles and preprints of cases of CNS demyelination associated with COVID-19 vaccines. Descriptive findings of reported cases were reviewed and stratified by demographic and clinical characteristics, diagnostic assessment, management, and overall outcome. Thirty-two cases were identified, with women accounting for the majority of cases (68.8%), and with a median age of 44 years. Eleven reported cases were in individuals who had received the Pfizer vaccine, eight who received the AstraZeneca vaccine, six the Moderna, five the Sinovac/Sinopharm, and one who received the Sputnik vaccine followed by the Johnson & Johnson vaccine. Most cases (71.8%) occurred after the first dose of vaccine, with neurological symptoms manifesting after a median of nine days. The most common presentations were transverse myelitis (12/32), and multiple sclerosis-like imaging (initial diagnosis or relapse) in another 12/32 cases, followed by disorders similar to acute disseminated encephalomyelitis (5/32) and to neuromyelitis optica spectrum disorder (3/32). In 17/32 (53.1%) of cases, a history of immune-mediated disease was reported. Demyelinating syndromes were most often reported in association with mRNA vaccines (17/32), followed by viral vector vaccines (10/32) and inactivated vaccines (5/32). Most multiple sclerosis-like episodes reported (9/12) were triggered by mRNA-based vaccines, while transverse myelitis occurred following vaccination with viral-vector and mRNA vaccines. Treatment included high doses of methylprednisolone, plasma exchange, intravenous immunoglobulin, or a combination of these, with favorable outcomes in most cases and marked or complete improvement (25/32), with stabilization or partial recovery in the remaining cases. The authors, through this systematic review, identified few cases of CNS demyelination following any of the currently approved COVID-19 vaccines. The clinical presentation was heterogeneous, mainly after the first dose; however, half of the published cases included a history of immune-mediated disease. Most cases had a favorable outcome. Long-term post-marketing surveillance is suggested for these cases, in order to assess causation and ensure the safety of COVID19 vaccines.
Source: Ismail II, Salama S. A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2021 Nov 9;362:577765. doi: 10.1016/j.jneuroim.2021.577765. Online ahead of print. PMID: 34839149; PMCID: PMC 8577051. Available at: https://www.jamda.com/article/S1525-8610(20)30371-6/fulltext
Immunogenicity and Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis
On 26 October, a systematic review and meta-analysis was published, with the aim of assessing the immune response after vaccination against COVID-19 of the population with cancer compared to the population without cancer. A search was conducted of the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from 1 March 2020 to 12 August 2021. Primary end-points were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T cell response, and documented SARS-CoV-2 infection after COVID19 immunization. Overall effects were pooled using random-effects models. This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval, 41–62) and 73% (95% CI, 64–81) of patients with cancer developed anti-S IgG above the threshold level after partial and complete immunization, respectively. Patients with hematologic malignancies had a significantly lower seroconversion rate than those with solid tumors after complete immunization (65% vs. 94%; P < 0.0001). Compared with controls, patients with cancer with an incomplete vaccination schedule had a 55% reduced likelihood of achieving anti-S IgG titers above the threshold level (RR 0.45; 95% CI 0.35– 0.58), whereas a 31% reduced likelihood of seroconversion was documented among those with a complete vaccination schedule (RR 0.69, 95% CI 0.56–0.84). Moreover, when compared with non-cancer controls, oncological patients had a tendency towards increased documented SARS-CoV-2 infection after partial (RR 3.21; 95% CI 0.35–29.04) and complete COVID-19 immunization (RR 2.04; 95% CI 0.38–11.10). Patients with cancer had an impaired immune response to COVID-19 vaccination compared with controls. Strategies that endorse the completion of vaccination schedules are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients’ immune response.
Source: Becerril-Gaitan A, Vaca-Cartagena BF, Ferrigno AS, et al. Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis. Eur J Cancer. 2021 Oct 26:S0959– 8049(21)01168–0. doi:10.1016/j.jinf.2020.02.028. Online ahead of print. PMID: 34794855; PMCID: PMC8548030. Available at: https://www.ejcancer.com/article/S0959-8049(21)01168-0/fulltext
Association between vaccination with the BNT162b2 mRNA COVID-19 vaccine and Bell's palsy: a population-based study
On 4 November, a cohort study was published examining the association between the BNT162b2 mRNA COVID-19 vaccine and Bell's palsy. Using the database of the largest healthcare provider in Israel, the authors retrieved data from different periods in 2018-2021. Observed cases of Bell's palsy occurring within 21 days after the first vaccine dose and within 30 days after the second vaccine dose were compared to the expected cases, based on the experience of the population in 2019. Standardized incidence ratios (SIRs) and attributable risks (ARs) were computed.
Overall, 132 cases of Bell's palsy were reported among 2,594,990 individuals after vaccination with a first dose, and
152 cases among 2,434,674 individuals after receiving a second dose. The age and sex weighted SIRs were 1.36 (1.14-1.61) and 1.16 (0.99-1.36) after the first and second vaccine dose, respectively. SIRs tended to be higher in older age groups after the first and second vaccine doses. The estimates were more pronounced in older females after the first vaccine dose; SIR=1.71 (1.10-2.54) at ages 45-64, and 2.51 (1.65-3.68) at age ≥65 years. The highest AR was 4.46 per 100,000 individuals vaccinated, detected in females aged ≥65 years. In patients with a previous history of Bell's palsy, only 4 cases of Bell's palsy were reported in 7,567 individuals vaccinated and 10 cases in 7,045 individuals vaccinated after the first and the second dose, respectively. The age- and sex-weighted SIRs were 1.15 (0.36-2.76) and 2.15 (1.09-3.83) after the first and second vaccine dose, respectively. The authors conclude that this study suggests that the BNT162b2 mRNA COVID-19 vaccine might be associated with increased risk of Bell's palsy. The small estimated attributable risks suggest that the impact on public health is relatively minor. The benefits of vaccinations explicitly outweigh the possible link to Bell's palsy, which has high recovery rate if timely treated with corticosteroids.
Source: Shibli R, Barnett O, Abu-Full Z, et al. Association between vaccination with the BNT162b2 mRNA COVID-19 vaccine and Bell's palsy: a population-based study. Lancet Reg Health Eur. 2021 Dec;11:100236. doi: 10.1016/j.lanepe.2021.100236. Epub 2021 November 4. PMID: 34751262; PMCID: PMC8566165. Available at: https://www.sciencedirect.com/science/article/pii/S2666776221002222?via%3Dihub
Thrombotic Events after COVID-19 Vaccination in the Over-50s: Results from a Population-Based Study in Italy
On 10 November, a cohort study was published to evaluate post-vaccination thrombotic events in patients over 50 years of age. The study mentions that several European countries suspended or changed recommendations for the use of Vaxzevria (AstraZeneca) for suspected adverse effects due to atypical blood-clotting. This research aimed to identify the number of expected thrombotic events in the Italian population over the age of 50 that received the Vaxzevria vaccine between 22 January and 12 April 2021. The venous thromboembolism (VT) and immune thrombocytopenia (IT) event rates were estimated from a population-based cohort. The overall VT rate was 1.15 (95% CI 0.93–1.42) per 1,000 person-years, and the ITP rate was 2.7 (95% CI 0.7–11) per 100,000 person-years. These figures translate into 83 VT events and 2 ITP events, in the 15 days following the first administration of Vaxzevria. The number of thrombotic events reported from the Italian Medicines Agency does not appear to have increased beyond that expected in individuals over 50 years of age. The authors conclude that these findings contribute to the ongoing discussion about vaccine safety, particularly for adenovirus-based vaccines, where the occurrence of coagulationrelated disorder constitutes a significant concern.
Source: Baldi I, Azzolina D, Francavilla A, et al. Thrombotic Events after COVID-19 Vaccination in the Over-50s:
Results from a Population-Based Study in Italy Vaccines (Basel). 2021 Nov 10;9(11):1307. doi:
10.3390/vaccines9111307. PMID: 34835237; PMCID: PMC8620372. Available at: https://www.mdpi.com/2076393X/9/11/1307
Risk-benefit analysis of the AstraZeneca COVID-19 vaccine in Australia using a Bayesian network modelling framework
On 4 November, a study was conducted using a Bayesian model, which provided a risk-benefit analysis of the AstraZeneca vaccine. This study was based on the fact that thrombosis with thrombocytopenia syndrome (TTS) has been associated with the AstraZeneca (AZ) COVID-19 vaccine (Vaxzevria). Australia has reported low TTS incidence of < 3/100,000 after the first dose, with a case fatality rate (CFR) of 5%–6%. Risk-benefit analysis of vaccination has been challenging because of rapidly evolving data, changing levels of transmission, and variation in rates of TTS, COVID-19, and CFR between different age groups. The aim of the authors was to optimize risk–benefit analysis by developing a model that enables inputs to be updated rapidly as evidence evolves. A Bayesian network was used to integrate local and international data, government reports, published literature, and expert opinion. The model estimates probabilities of outcomes under different scenarios of age, sex, low/medium/high transmission (0.05%/0.45%/5.76% of population infected over 6 months), SARS-CoV-2 variant, vaccine dose, and vaccine effectiveness. The authors used the model to compare estimated deaths from AZ vaccine-associated TTS with (i) COVID-19 deaths prevented under different scenarios; and (ii) deaths from COVID-19-related atypical severe blood clots (cerebral venous sinus thrombosis and portal vein thrombosis). For a million people aged ≥ 70 years where 70% received a first dose and 35% received two doses, the model estimated < 1 death from TTS, 25 deaths prevented under low transmission, and > 3,000 deaths prevented under high transmission. Risks versus benefits varied significantly between age groups and transmission levels. Under high transmission, deaths prevented by AZ vaccine far exceed deaths from TTS (by 8 to > 4,500 times depending on age). Probability of dying from COVIDrelated atypical severe blood clots was 58–126 times higher (depending on age and sex) than dying from TTS. The authors mention that this is the first example of the use of Bayesian networks for risk–benefit analysis for a COVID19 vaccine. The model can be rapidly updated to incorporate new data, adapted for other countries, extended to other outcomes (e.g., severe disease), or used for other vaccines.
Source: Lau CL, Mayfield HJ, Sinclair JE, et al. Risk-benefit analysis of the AstraZeneca COVID-19 vaccine in Australia using a Bayesian network modelling framework. Vaccine. 2021 Nov 4:S0264–410X(21)01428–6. doi: 10.1016/j.vaccine.2021.10.079. Online ahead of print. PMID: 34810000; PMCID: PMC8566665. Available at: https://www.sciencedirect.com/science/article/pii/S0264410X21014286?via%3Dihub