Surveillance of adverse events associated with 145 000 doses of COVID-19 vaccines in a Brazilian municipality.

There is a lack of real-world surveillance studies on reports of adverse events associated with COVID-19 vaccination, as well as comparative analyses of adverse events from vaccines with different platforms. This observational, descriptive, retrospective study based on secondary data describes the adverse events following immunization (AEFIs) related to the first 145 000 doses of COVID-19 vaccines delivered in Aracaju municipality, Sergipe state, northeast Brazil. Records of AEFIs were collected using the e-SUS Notifica database for January 19 to April 30, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for AEFIs and the type of COVID-19 vaccine, either CoronaVac (Sinovac-Butantan) or Oxford-AstraZeneca (Fiocruz). A total of 474 AEFIs (32.7 events/10 000 doses) from 254 individuals were reported and analyzed, and all of them were classified as non-serious. There was an association between the use of the CoronaVac vaccine and headache (OR = 2.1; 95% CI: 1.4-3.2), pain at the injection site (OR = 9.6; 95% CI: 3.9-23.8), lethargy (OR = 5.2; 95% CI: 1.8-14.8), fatigue (OR = 10.1; 95% CI: 2.4-42.3), diarrhea (OR = 4.4; 95% CI: 1.5-12.5) and cold-like symptoms (OR = 8.0; 95% CI: 1.9-34.0). However, the proportion of individuals reporting fever was higher among those who received the Oxford-AstraZeneca vaccine (OR = 3.1; 95% CI 1.5-6.4). This population-based observational study strengthens the evidence for the safety and tolerability of the CoronaVac and Oxford-AstraZeneca vaccines used against COVID-19.

Mass vaccination is the most cost-effective measure to control and prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The available vaccines have 50–95% effectiveness in preventing severe outcomes from coronavirus disease 2019 (COVID-19) and have been shown to be safe in clinical trials (1–5). Despite adverse events following immunization (AEFIs) being well documented in vaccine trials, post-approval surveillance of these is critical to improve safety and maintain public confidence in a vaccination program (6). There is a lack of real-world surveillance studies of AEFIs associated with COVID-19 vaccination, as well as a lack of comparative analyses of adverse events from vaccines using different platforms.

This observational, descriptive, retrospective study based on secondary data describes the AEFIs related to the first 145 000 doses of COVID-19 vaccines delivered in Aracaju municipality, Sergipe state, northeast Brazil. Aracaju is one of the poorest regions in the country, has an area of 182.2 km2, and has an estimated population of 657 053 inhabitants. On March 14, 2020, the first case of COVID-19 was identified in a female patient who had traveled to Spain; on April 2, 2020, the first death from the disease was officially confirmed. At the time of writing this manuscript in 2022, SARS-CoV-2 had infected 150 303 individuals and resulted in 2558 deaths. In Brazil, CoronaVac (a Sinovac–Butantan product) was the first vaccine approved for use against COVID-19 and was delivered primarily to elderly people, health care workers and members of Indigenous communities, all of whom were considered priority groups for immunization at the beginning of the vaccination campaign. In Aracaju, the first doses of the vaccine were administered on January 19, 2021. In early February 2021, the first doses of the Oxford–AstraZeneca vaccine (produced in Brazil by Fiocruz) were administered.

Records of AEFIs were collected using the e-SUS Notifica database for January 19 to April 30, 2021. The e-SUS Notifica database was launched in Brazil on March 27, 2020, and it has been used as a passive surveillance system by public and private health professionals to notify AEFIs occurring within 30 days of vaccination. If an adverse event occurs, the patient is followed up until it resolves. For this study, information about age, sex, type of COVID-19 vaccine, and AEFIs was extracted. Adverse events were classified as serious or non-serious. Serious adverse events included death, life-threatening illness, hospitalization or prolongation of hospitalization, and permanent disability. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for associations between AEFIs and the type of COVID-19 vaccine (CoronaVac vs. Oxford–AstraZeneca). In the case of zero events, a continuity correction of 0.5 was used. Analyses were performed using JASP software version 0.13 (JASP, Amsterdam, the Netherlands).

Between January 19 and April 30, 2021, 145 133 doses of COVID-19 vaccine were administered: 85 587 were CoronaVac and 59 546 were Oxford–AstraZeneca. A total of 474 AEFIs were reported (32.7 events/10 000 doses) from 254 individuals (mean age: 41 years; standard deviation: 9.8; 208/254 [81.9%] female) and analyzed, and all of them were classified as non-serious events. Of the 254 individuals with AEFIs, 221 (87%) received CoronaVac and 33 (13%) received Oxford–AstraZeneca. The most common AEFIs were headache (7.7 events/10 000 doses), pain at the injection site (5.1/10 000 doses), myalgia or arthralgia (3.3/10 000 doses), nausea or vomiting (2.6/10 000 doses), and fever (2.4/10 000 doses). We found an association between the use of CoronaVac and headache (OR = 2.1; 95% CI: 1.4–3.2; P < 0.001), pain at the injection site (OR = 9.6; 95% CI: 3.9–23.8; P < 0.001), lethargy (OR = 5.2; 95% CI: 1.8–14.8; P = 0.002), fatigue (OR = 10.1; 95% CI: 2.4–42.3; P = 0.002), diarrhea (OR = 4.4; 95% CI: 1.5–12.5; P = 0.006) and cold-like symptoms (OR = 8.0; 95% CI: 1.9–34.0; P = 0.005). However, the proportion of individuals reporting fever was higher among those who received the Oxford–AstraZeneca vaccine (OR = 3.1; 95% CI: 1.5–6.4; P = 0.002) (Table 1).

TABLE 1.

Association between adverse events following immunization and type of COVID-19 vaccine, Brazil, 2021

Type of adverse event following immunization	Type of COVID-19 vaccine						OR (95% CI)	P value
	Both types (N = 145 133 doses)		CoronaVac (Sinovac–Butantan) (n = 85 587 doses)		Oxford–AstraZeneca (Fiocruz) (n = 59 546 doses)
	n	No. of events/10 000 doses	n	No. of events/10 000 doses	n	No. of events/10 000 doses
Headache	112	7.7	84	9.8	28	4.7	2.1 (1.4–3.2)	< 0.001
Pain at injection site	74	5.1	69	8.1	5	0.8	9.6 (3.9–23.8)	< 0.001
Myalgia or arthralgia	48	3.3	27	3.2	21	3.5	1.1 (0.6–2.0)	0.702
Nausea or vomiting	38	2.6	26	3.0	12	2.0	1.5 (0.8–3.0)	0.240
Fever	35	2.4	11	1.3	24	4.0	3.1 (1.5–6.4)	0.002
Drowsiness or lethargy	34	2.3	30	3.5	4	0.7	5.2 (1.8–14.8)	0.002
Fatigue	31	2.1	29	3.4	2	0.3	10.1 (2.4–42.3)	0.002
Diarrhea	29	2.0	25	2.9	4	0.7	4.4 (1.5–12.5)	0.006
Cold-like symptoms	25	1.7	23	2.7	2	0.3	8.0 (1.9–34.0)	0.005
Abdominal pain	20	1.4	16	1.9	4	0.7	2.8 (0.9–8.3)	0.067
Local reaction (erythema, induration, swelling)	16	1.1	10	1.2	6	1.0	1.2 (0.4–3.2)	0.774
Dizziness	9	0.6	8	0.9	1	0.2	5.6 (0.7–44.5)	0.106
Shortness of breath	2	0.1	2	0.2	0	0.0	3.5 (0.2–72.5)	0.421
Lymphadenopathy	1	0.1	1	0.1	0	0.0	2.1 (0.1–51.2)	0.652

CI: confidence interval; OR: odds ratio.

In this real-world surveillance study, we observed a rate of approximately 33 adverse events per 10 000 doses of COVID-19 vaccine during the first 3 months of the vaccination campaign in a Brazilian municipality. Despite the rate of AEFIs being lower than that shown in previous Phase 1 and 2, randomized controlled trials (7, 8), our findings also demonstrated that adverse events were mild and self-limited and included primarily headache and local pain at the injection site. Moreover, no life-threatening complications were reported, which indicates that these vaccines are well tolerated and have minor safety issues.

Although associations between specific vaccine platforms and adverse events are poorly understood, viral vector vaccines carry information that might be critical for the enhancement of proinflammatory cytokines, leading to an intense systemic response (9). In this study, immunization with Oxford–AstraZeneca – a replication-deficient chimpanzee adenovirus–vector vaccine encoding the SARS-CoV-2 Spike glycoprotein – was strongly associated with the occurrence of fever. This finding is in agreement with a previous study from Thailand that found a higher frequency of individuals reporting fever after vaccination with the chimpanzee adenovirus–vector vaccine compared with those receiving a whole-cell inactivated vaccine (10). However, in our study, individuals receiving the inactivated SARS-CoV-2 vaccine were more likely to experience headache, local pain, lethargy, fatigue, diarrhea and cold-like symptoms.

Our results should be interpreted with caution due to the inherent limitations of spontaneous (passive) surveillance and the lack of analysis of sex- and age-based differences regarding the adverse events. However, this population-based observational study reinforces the safety and tolerability of the CoronaVac and Oxford–AstraZeneca vaccines used against COVID-19.

Disclaimer.

Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the Revista Panamericana de Salud Pública/Pan American Journal of Public Health or those of the Pan American Health Organization (PAHO).