OFFICIAL REPORTS ON PHARMACOVIGILANCE PROGRAMS - 8 November 2021
BRAZIL (State of Rio Grande do Sul)
- In the period from 18 January to 18 September 2021, a total of 13,053,922 doses of COVID-19 vaccines were administered in the State of Rio Grande do Sul: 6,126,758 doses of Covishield (Oxford/AstraZeneca/Fiocruz), 4,125,951 doses of CoronaVac (Sinovac/Butantan), 2,500,115 doses of Comirnaty (Pfizer/Wyeth), and 301,098 doses of the Janssen-Cilag (Ad26.COV2-S [recombinant]) vaccine.
- From 18 January to 18 September 2021, there were 13,020 reports of suspected adverse events following immunization (AEFI) (0.1% of doses administered). Of these, 2,016 involved immunization errors, 1,074 reported a diagnosis of COVID-19, and 9,930 were confirmed AEFI.
- The number of reports, by producing laboratory, were: 7,009 for Covishield (Oxford/AstraZeneca/Fiocruz), 2,222 for CoronaVac (Sinovac/Butantan), 542 for Comirnaty (Pfizer/Wyeth), and 157 for the Janssen-Cilag vaccine. Incidence per 100,000 doses administered was as follows: 114.4 for Covishield, 53.9 for CoronaVac, 21.7 for Comirnaty, and 52.1 for Janssen-Cilag.
- A higher number of reported adverse events were in women (7,358) than in men (2,572).
- Among the 9,930 individuals who reported at least one adverse event, a total of 27,762 events (signs and symptoms) were reported.
- In terms of the severity of the adverse events, 27,058 (97.5%) were classified as non-serious, and 704 (2.5%) as serious.
- Among the non-serious adverse events, the most common ones associated with the Covishield (AstraZeneca/Fiocruz) vaccine were fever, headache, myalgia, chills, and nausea; for CoronaVac (Sinovac/Butantan), headache, myalgia, diarrhea, fever, and sore throat; for Comirnaty (Pfizer/Wyeth), headache, myalgia, fever, cough, and nausea; and for the Janssen-Cilag vaccine, the most common adverse events were fever, headache, myalgia, fatigue, and chills.
- The highest incidence of reported serious events temporally associated with vaccination for the Covishield (AstraZeneca/Fiocruz) vaccine were headache, fever, dyspnea, death, and Guillain-Barré syndrome; for CoronaVac (Sinovac/Butantan), death, dyspnea, cerebrovascular accidents (CVA), acute myocardial infarction (AMI), and fever; for Comirnaty (Pfizer/Wyeth), headache, vomiting, myelitis, and fever; and for the Janssen-Cilag vaccine, headache, neurological disorders, dysarthria, dysphagia, and acute disseminated encephalomyelitis.
- A total of 120 thromboembolic events were reported. These included 83 cases (1.35/100,000 doses administered) after vaccination with the Covishield (AstraZeneca/Fiocruz) vaccine, 28 (0.28/100,000 doses) with CoronaVac (Sinovac/Butantan), 6 (0.24/100,000 doses) with Comirnaty (Pfizer/Wyeth), and 3 (1.00/100,000 doses) after vaccination with the Janssen-Cilag vaccine. Among the cases clinically classified as thromboembolic events were 45 cases of cerebrovascular accidents, 3 cases of acute myocardial infarction, 2 cases of pulmonary thromboembolism, 9 cases of thrombophlebitis, and 61 cases of thrombosis, including deep vein thrombosis, limb arterial thrombosis, mesenteric venous thrombosis, cerebral thrombosis, embolism and thrombosis of unspecified veins, embolism and other aortic thrombosis, and unspecified thrombosis.
- There were 190 reported deaths, of which 186 are still under investigation. Of the four deaths investigated for which causality was determined, one remains unclassifiable due to lack of supplementary data, one was temporally associated with vaccination, and two, which were inconsistent or coincident with vaccination, were determined not have a causal relationship with the vaccines, due to pre-existing or emerging conditions.
As of 5 November 2021, 40,654,538 doses of the Pfizer-BioNTech COVID-19 vaccine, 14,254,199 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 22,280 individual reports of one or more AEFI (0.038% of doses administered) were received. Of these, 5,699 reports involved serious AEFI (0.010% of doses administered).
In all, 59,370 adverse events following immunization were reported (22,280 reports involving one or more events). Most of the adverse events were non-serious, and included paresthesia, injection-site reactions, headache, pruritus, fatigue, dyspnia, urticaria, erythema, etc.
Source: Public Health Agency of Canada. Canadian COVID-19 vaccine safety report. Ottawa: Public Health Agency of Canada. November 5, 2021. https://health-infobase.canada.ca/covid-19/vaccine-safety/. Data reproduced by PAHO/WHO.
- In the October bulletin of INVIMA, which covers the reporting period for adverse events following immunization (AEFI) from 17 February to 15 October 2021, there were 23,625 reports of AEFI, out of a total 44,350,661 doses of vaccines administered, representing a reporting rate of 53 per 100,000 doses administered.
- The distribution of reports, by vaccine manufacturer, as of 15 October 2021 was: 13,284 reports for the Pfizer vaccine (95.3 per 100,000 doses administered), 5,223 for SinoVac (33.4 per 100,000 doses administered), 2,385 for AstraZeneca (36.2 per 100,000 doses administered), 1,648 for Janssen (18.7 per 100,000 doses administered), 1,041 for Moderna (5.5 per 100,000 doses administered), and 44 reports for which the vaccine manufacturer was not identified.
- The distribution of events, by sex, was 71% in women and 29% in men. Of reported events, 22,675 (96%) were classified as non-serious and 950 (4%) as serious.
- The most frequently reported signs and symptoms were headache (25.1%), injection-site pain (11.1%), dizziness (9.2%), muscle pain (9.0%), fever (8.4%), and malaise (8%).
- As of 10 November 2021, following the administration of more than 401 million doses of mRNA vaccines (PfizerBioNTech and Moderna) in the United States, only two cases of thrombosis with thrombocytopenia syndrome (TTS), associated with the Moderna vaccine, had been reported to VAERS. Given the available information, there does not appear to be an increased risk of TTS following vaccination with mRNA COVID-19 vaccines.
- As of 27 October, more than 15.5 million doses of the J&J/Janssen COVID-19 vaccine had been administered. The Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) have identified 48 confirmed reports of people who received the J&J/Janssen vaccine and subsequently developed TTS. Women under the age of 50 should be alerted to the rare but increased risk of this adverse event. There are other COVID-19 vaccine options available for which this risk has not been seen.
- Following the administration of more than 15.5 million doses of the Janssen vaccine, approximately 244 preliminary reports of Guillain-Barré syndrome had been identified, as of 27 October 2021. These cases have mostly been reported approximately two weeks after vaccination and primarily in men, many ages 50 and older.
- As of 27 October, VAERS had received 1,784 reports of myocarditis or pericarditis among people 30 years of age or younger who had received a COVID-19 vaccine. Most cases have been reported after mRNA COVID-19 vaccination (Pfizer-BioNTech or Moderna), particularly in male adolescents and young adults.
- Reports of deaths following vaccination with COVID-19 vaccines are rare. More than 423 million doses of COVID19 vaccines were administered in the United States between 14 December 2020 and 1 November 2021. During this time, VAERS received 9,367 reports of death (0.0022%) among people who received a COVID-19 vaccine.
- On 29 October, the thirty-fourth AEFI surveillance report of the Paraguayan Ministry of Health indicated that, during the period from 22 March to 29 October, 5,289,784 doses of COVID-19 vaccines had been administered to 2,919,120 people.
- Between 22 February 29 October 2021, there were 2,325 reports of AEFI (0.05% of total doses administered). Of these, 379 cases were considered serious.
- Among the AEFI reported, 71.7% (1,667) were in women; 68.7% (1,610) were in people between the ages of 25 and 49. Additionally, among all AEFI reported, 49.3% (1,149) were for people who received the AstraZeneca vaccine, followed by 15.1% (352) for the Sputnik V vaccine, 14.1% (330) for the Pfizer/BioNTech vaccine, 7.8% (182) for CoronaVac, 6.7% (156) for COVAXIN, 4.6% (108) for Moderna, and 2.1% (49) for the Sinopharm vaccine.
Publications on potential safety signals identified with the use of COVID-19 vaccines
Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis
A systematic review and meta-analysis of anaphylactic and nonanaphylactic reactions following SARS-CoV-2 vaccines in the general adult population was published on 16 October. Its objective was to estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and to describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment, and clinical course of confirmed cases. The authors searched electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) for English-language entries from 1 December 2020 to 31 May 2021. Of the 1,734 articles identified, 26 were included in the systematic review (8 case reports, 5 cohort studies, 4 case series, 2 randomized controlled trials, and one randomized cross-sectional study), while 14 articles were included in the meta-analysis (one cohort study, 2 case series, one randomized controlled trial, and one randomized cross-sectional study). Studies involving 26,337,421 vaccine recipients (Pfizer-BioNTech [n = 14,505,399] and Moderna [n = 11,831,488]) were analyzed. The overall pooled prevalence estimate of anaphylactic reactions to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. Previous history of anaphylaxis and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis, and cholinergic urticaria were also found to be important. The authors conclude that the prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low, while nonanaphylactic reactions occur at a higher rate; cutaneous reactions, however, are largely self-limited. Neither anaphylactic nor nonanaphylactic reactions should discourage vaccination.
Source: Alhumaid S, Al Mutair A, Al Alawi Z, et al. Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis. Allergy Asthma Clin Immunol. 2021 Oct 16;17(1):109. doi: 10.1186/s13223–021-00613–7. PMID: 34656181; PMCID: PMC8520206. Available at: https://aacijournal.biomedcentral.com/articles/10.1186/s13223-021-00613-7.
Systemic autoimmune myopathies: A prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2
On 19 October, an online pre-print cohort study, with a control group, was published, with the objective of evaluating immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities, and therapy on immune response. This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised individuals as a control group (CTRL). All participants received two doses of the CoronaVac-Sinovac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titer (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR-confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Patients and CTRL were of comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed, at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT (7.9 [95%CI 4.7–13.2] vs 24.7 [95%CI 30.0–30.5] UA/ml, P<0.001) and frequency of NAb (51.4% vs 77.2%, P<0.001). Median neutralizing activity was comparable in both groups (57.2% [interquartile range (IQR) 43.4–83.4] vs 63.0% [IQR 40.3–80.7], P=0.808). Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs, or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild, with similar frequencies in patients and CTRL (P>0.05). The authors conclude that, based on this study, CoronaVac-Sinovac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. They further identified that immunosuppression is associated with diminished NAb positivity.
Source: Shinjo SK, by Souza FHC, Borges IBP, et al. Systemic autoimmune myopathies: A prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2. Rheumatology (Oxford). 2021 Oct 19:keab773. doi: 10.1093/rheumatology/keab773. Pre-print e-pub. PMID: 34664616. Available at: https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab773/6402018.
Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in a subgroup of healthy adults in Chile
On 19 September, an online pre-print article was published, reporting safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 in a phase 3 clinical trial of the inactivated COVID-19 vaccine CoronaVac. Volunteers randomly received two doses of CoronaVac or placebo, separated by two weeks; 434 volunteers were enrolled, 397 aged 18-59 years, and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-RBD IgG were 86.67% in the 18-59 age group and 70.37% in the ≥60 age group, two and four weeks after the second dose. A significant increase in circulating neutralizing antibodies was detected two and four weeks after the second dose. The cellular evaluation was performed on 47 volunteers. The authors detected a significant induction of T-cell responses characterized by the secretion of IFN-gamma upon stimulation with Mega Pools of peptides from SARS-CoV-2. The authors conclude that immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T-cells, and promotes the secretion of IFN-gamma upon stimulation with SARS-CoV-2 antigens.
Source: Bueno SM, Abarca K, González PA, et al. Safety and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine in a Subgroup of Healthy Adults in Chile. Clin Infect Dis. 2021 Sep 19:ciab823. doi: 10.1093/cid/ciab823. Pre-print epub. PMID: 34537835. Available at: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab823/6372423.
Reactogenicity to a third dose of mRNA vaccine (BNT162b2) in immunocompromised individuals and people over 60 years of age – a nationwide survey in Israel
On 24 September, an online pre-print retrospective cohort study, without a control group, was published. The objective of the study was to evaluate reactogenicity of the BNT162b2 vaccine, after administering a third dose to immunocompromised individuals and people 60 years old or older (approved in Israel on 13 July 2021). A retrospective cohort, using electronic surveys sent to booster vaccine recipients, between 20 July and 10 August 2021, was analyzed. A total of 17,820 people participated in the survey, with a response rate of 30.2%; 3,195 (17.9%) were immunocompromised. Fatigue, myalgia, and fever were the most frequent systemic side effects reported (19.6%, 9.2%, and 8.1%, respectively among immunocompromised; 21.3%, 9.9%, and 9.2%, respectively among seniors). 67.3% of immunocompromised and 62% of seniors reported experiencing a better or a similar response to the third dose, compared to the second. The authors conclude that local and systemic reactions after a third vaccination with SARSCoV-2 vaccine BNT162b, reported by immunocompromised and seniors, were similar to those observed following previous vaccines and mostly self-resolved. These findings may aid in promoting confidence among vaccine providers and recipients.
Source: Shapiro Ben David S, Shamir-Stein N, Baruch Gez S, et al. Reactogenicity of a third BNT162b2 mRNA COVID19 vaccine among immunocompromised individuals and seniors - A nationwide survey. Clin Immunol. 2021 Sep 24;232:108860. doi: 10.1016/j.clim.2021.108860. Pre-print e-pub. PMID: 34571262; PMCID: PMC8461972. Available at: https://www.sciencedirect.com/science/article/pii/S1521661621001972?via%3Dihub.