DOI: https://doi.org/10.21203/rs.3.rs-1748827/v1
Tracking of adverse events following vaccination is important for evaluating vaccine safety. During March 2021, Uganda began COVID-19 vaccination using the Astra-Zeneca vaccine targeting teachers, health workers, security personnel, and the elderly. We assessed adverse events following AstraZeneca vaccination in Greater Kampala, Uganda to track the safety of the vaccine.
We used vaccination registers to identify persons who received ≥ 1 dose of the AstraZeneca COVID-19 vaccine during March 10–April 30, 2021. Adverse events following vaccination were defined as an untoward medical occurrence after vaccination (not necessarily causally related to the vaccine). Serious adverse events were defined as any event considered life-threatening, resulting in hospitalization, persistent disability ˃28 days, death, or congenital anomaly. We extracted telephone contacts for a systematic random sample of vaccinated individuals and their next of kin where necessary. We then conducted phone interviews to collect data on demographics and details of adverse events where they occurred. We used logistic regression analysis to establish relationships between variables and our outcome of interest (developing an adverse event following vaccination).
Among 374 subjects interviewed, mean age was 41 years; range 20–85 years; 176 (47%) were female. Of these, 235 (63%) received only one dose and 139 (37%) received two doses. In total, 516 adverse events occurred in 286 (77%) individuals, including in 255 (68%) individuals after the first dose and in 45 (32%) individuals after the second. The most common adverse events were redness/pain/itching at the injection site (34%) and headache (32%). None of the events were classified as serious. Persons aged 20–29 years (AOR 4.7; 95% CI: 2.0–10.2), 30–39 years (AOR 3.7; 95% CI: 1.8–7.4) and 40–49 years (AOR 2.8; 95% CI 1.3–5.0) were more likely to develop adverse events than those aged ≥ 50 years.
Most individuals experienced ≥ 1 adverse event. No serious adverse events were reported. Younger age (˂50 years) was associated with adverse event. We recommend use of the AstraZeneca COVID-19 vaccine in Uganda based on its safety.
On March 11, 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). To slow the spread of SARS-CoV-2, nations around the world implemented different control measures. These measures included social distancing, partial and comprehensive lockdowns, closing of schools and businesses, and wearing face masks in public (2). Although such measures helped in flattening the epidemic curve, the resurgence of COVID-19 was reported as societies and economies reopened (3). Hence, there was an urgent need for vaccination as a long-term preventive measure to address COVID-19 (4).
In November 2020, the first vaccines to address COVID-19 were approved (5). Since then, several vaccines have been rolled out in countries, and more than 200 additional vaccine candidates are still in development (6). The most commonly used vaccines include the AstraZeneca, Moderna, BioNTech, Pfizer, Johnson & Johnson, Sinopharm, and Gamaleya vaccines (7).
Following vaccination, adverse events can occur within seconds to weeks (8). Adverse events following vaccination are events that follow vaccination but may not necessarily have a causal relationship with usage of the vaccine (8, 9). Adverse events can be categorized as serious and non-serious. Serious adverse events are events that result in death, hospitalization, a permanent/persistent disability, or congenital anomalies/defects. Non-serious adverse events are events that do not meet the criteria for serious events (10, 11).
In March 2021, the Uganda Ministry of Health (MoH) started the vaccination exercise using the AstraZeneca COVID-19 vaccine, and distribution to all districts was done (12). The target group for vaccination included: teachers, health workers, security personnel, humanitarian front-line workers, the elderly (≥ 50 years), and those aged 18–49 years with comorbidities (13). In order to track adverse events, the MoH instituted active surveillance for adverse events as recommended by the World Health Organization (WHO) in the post-authorization/Emergency Use Listing period (14). Tracking of adverse events following vaccination is important for evaluating the safety of vaccines. Expected adverse events for the AstraZeneca COVID-19 vaccine included injection site events, headaches, fever and malaise among others (15). With the AstraZeneca vaccine in particular, concern were raised by scientists in Europe about serious adverse events such as deaths, clots, and severe allergic reactions (16).
Although the Uganda MoH and WHO assured the public that the AstraZeneca vaccine is safe and effective against COVID-19 (17), no study had been done to fully evaluate adverse events experienced with the vaccine in Uganda. We sought to describe the adverse events experienced following AstraZeneca COVID-19 immunization and to determine the factors associated with adverse events in Greater Kampala, Uganda, to help track the safety of the vaccine.
We defined a serious adverse event as any medical occurrence that resulted in hospitalization or was considered life-threatening in an individual who received at least one dose of the AstraZeneca COVID-19 vaccine from a vaccination site in Greater Kampala, Uganda during 10 March–30 April 2021. A non-serious adverse event was defined as one that does not meet the criteria for serious adverse events.
Study design and setting
We conducted a cross-sectional study on the experiences of people who received at least one dose of the COVID-19 vaccine using quantitative data collection methods. We conducted the study in Kampala, Wakiso, and Mukono districts, districts that make up Greater Kampala. These districts were chosen because they had the highest proportion of individuals who had received the COVID-19 vaccine at the time, with Kampala (15%), Mukono (2%), and Wakiso (1.7%). Early during the vaccination exercise, the Uganda MoH gazetted COVID-19 vaccination sites in each district. Kampala had five vaccination sites in each of the five divisions of Kampala, a total of 25 vaccination sites. Wakiso and Mukono districts had five vaccination sites each.
Sample size and sampling procedure
All the 35 vaccination sites located within the study area were considered for the study. The sample size for the participants was determined using the Kish Leslie (1964) formula, assuming a 95% confidence Interval, 50% estimated incidence of adverse events, and a margin of error (precision) of 0.05. Based on these assumptions, we estimated that we would need to include 384 individuals for which we inflated this number by 15% to account for non-response.
For each of the vaccination sites, we established the proportions of participants who would qualify for the study using probability proportionate to size of vaccinated individuals. At the time of data collection, approximately 36,000 individuals had received the AstraZeneca vaccine in Kampala, Wakiso, and Mukono. We apportioned our sample size among the 35 vaccination sites based on the number who had received the vaccine at each of the vaccination sites. We selected 355 individuals from 25 vaccination sites in Kampala District; 47 individuals from five vaccination sites in Mukono District and 40 individuals from five vaccination sites in Wakiso District. We then applied systematic sampling with a random start to identify the individuals who qualified for the study.
Study variables and data collection
Using a standardized questionnaire adapted from the WHO core variables for adverse events (9), we conducted phone interviews with the randomly sampled AstraZeneca vaccinated individuals. The primary outcome variable for this study was experiencing an adverse event following vaccination that could occur within seconds to weeks after vaccination. We collected data on demographic characteristics (age, sex, nationality, profession), individual clinical characteristics (having a chronic illness, ever had previous reactions to a vaccine, usually have reactions to medicine and illness at the time they received the vaccine) and details of the adverse events where they occurred. Data collected on adverse events included: adverse events experienced, the dose after which they occurred, time of onset, duration, and outcome of the adverse events.
Data analysis
For our data analysis, we entered data on demographics, individual clinical characteristics, and details of adverse events where they occurred into Excel and analyzed this data using SPSS. We described the study participants using frequencies and percentages and presented the data in tables. We fitted a binary logistic regression model to establish the association between the categorical independent variables and the outcome of interest (experiencing an adverse event following vaccination). First, at bivariate analysis, we considered a 10% level of significance and determined the crude odds ratios at 95% confidence interval (CI) and their respective p-values. All variables with p-values <0.05 were considered significant and selected for multivariable analysis. At multivariable analysis, we established adjusted odds ratios with their respective 95% CI and p-values. Variables with p-values <0.05 at multivariable analysis were significant and associated with the outcome.
Demographic and clinical characteristics of participants during a study to assess adverse events following vaccination with AstraZeneca, Greater Kampala, Uganda, March–April 2021
A total of 374 participants were interviewed. The mean age of the participants was 41 years (range 20–85), SD 13 years. Males made up half of the participants, 198 (53%); teachers, health workers, and security personnel formed a total of 161 (43%) of the participants (Table 1).
Variables | Frequency, n (%) | |
---|---|---|
Health facility/vaccination site | ||
Kampala | 307 | (82) |
Mukono | 36 | (10) |
Wakiso | 31 | (8) |
Age group (years) | ||
20–29 | 73 | (20) |
30–39 | 113 | (30) |
40–49 | 90 | (24) |
Sex | 98 | (26) |
Male | 198 | ((53) |
Female | 176 | (47) |
Nationality | ||
Ugandan | 365 | (98) |
Non–Ugandan | 9 | (2) |
Profession | ||
Health workers | 67 | (18) |
Teacher | 83 | (22) |
Security officers | 11 | (3) |
Others | 213 | (57) |
Have chronic illness | ||
Yes | 104 | (28) |
No | 270 | (72) |
Currently on any long-term medication | ||
Yes | 70 | (19) |
No | 304 | (81) |
Ever had previous reactions to vaccinations | ||
Yes | 19 | (5) |
No | 330 | (88) |
Not sure | 25 | (7) |
Usually have reactions to any medicine such as antibiotics, anti-inflammatories | ||
Yes | 47 | (13) |
No | 327 | (87) |
Illness at the time you received the COVID-19 vaccine | ||
Yes | 22 | (6) |
No | 352 | (94) |
Proportion of individuals that experienced adverse event(s) following vaccination with AstraZeneca, Greater Kampala, Uganda, March–April 2021
Among the participants, 255 (68%) experienced at least one event after the first dose and 45 (32%) experienced at least one event after the second dose; 268 (77%) had some form of adverse event after either dose. The most reported adverse events following the first dose were: redness/pain/itching at injection site, 92 (36%); headache, 88 (35%); and fever, 56 (22%) (Fig. 1). The most reported adverse events following the second dose were: fever, 11 (24%); redness/pain/itching at injection site, 9 (20%); and headache, 8 (18%) (Fig. 2). Overall, injection site events 101 (34%) and headache 96 (32%) were the most experienced adverse events. In the “Others” category, events such as skin rash, insomnia, limb paresis (mild/partial paralysis) and limb paraesthesia (burning or tingling sensation) were reported.
Time of onset of adverse events following vaccination with AstraZeneca, Greater Kampala, Uganda, March–April 2021
Most adverse events 146 (32%) after the first dose and most adverse events after the second dose 17 (28%) commenced within 1–6 hours (Fig. 3). Generally, most adverse events after the first and second dose commenced within the first 72 hours, 434 (95%) and 56 (93%) respectively (Fig. 4). Twenty-three (5%) and 4 (7%) of the events after the first and second dose respectively commenced after 72 hours of receiving the vaccines (Fig. 3).
Two hundred fifty-two (55%) of the events after the first dose and 33 (55%) of the events after the second dose lasted for 1–3 days; while 36 (8%) of the events after the first dose and 6 (10%) of the events after the second dose lasted ˃7 days (Fig. 4).
Two hundred eighty-two (62%) of the events after the first dose and 36 (60%) of the events after the second dose were self-resolved. Twenty-four (5%) of the events after the first dose and 4 (7%) of the events after the second dose resulted in outpatient assessment (Fig. 5).
Factors associated with experiencing adverse events following vaccination with AstraZeneca COVID-19 vaccine, Greater Kampala, Uganda, March-April 2021
Age, sex, and currently being on long-term medication were associated with an adverse event at bivariate analysis level. Respondents who were aged 20–29 years (COR 5.3, 95% CI, 2.4–12), 30–39 years (COR 3.9, 95% CI 2.1–7.5) and 40–49 years (COR 2.8, 95% CI, 1.5–5.3) were more likely to develop an adverse event than respondents aged 50 years and above (Table 2). Females were more likely to develop an adverse event compared to males (COR 1.7, 95% CI, 1.02–2.7); and those who were not on long term medication were less likely to develop an adverse event than those who were on long term medication (COR 0.4, 95% CI, 0.2–0.8) (Table 2).
After controlling for confounders, age was found to be significantly associated with developing an adverse event. Those aged 20–29 years (AOR 4.7; 95% CI: 2.0–10.2), 30–39 years (AOR 3.7; 95% CI: 1.8–7.4) and 40–49 years (AOR 2.8; 95% CI 1.3–5.0) had more odds of developing an adverse event compared to those above 50 years old (Table 2). Odds of developing an adverse event increased with decreasing age (Table 2). Female sex and currently being on long-term medication were found not to be associated with developing an adverse event.
Variables | Adverse event, n (%) | No adverse event, n (%) | COR(95% CI) | AOR(95% CI) |
---|---|---|---|---|
Age group (years) | ||||
20–29 | 64 (22) | 9 (10) | 5.3(2.4–11.9)* | 4.7(2.0–10.2)* |
30–39 | 95 (33) | 18 (21) | 3.9(2.1–7.5)* | 3.7(1.8–7.4)* |
40–49 | 71 (25) | 19 (22) | 2.8(1.5–5.3)* | 2.8(1.3–5.0)* |
≥ 50 | 56 (20) | 42 (48) | 1.0 | 1.0 |
Sex | ||||
Male | 143 (50) | 55 (63) | 1.0 | 1.0 |
Female | 143 (50) | 33 (38) | 1.7(1.02–2.7)* | 1.6(0.93–2.6) |
Nationality | ||||
Non–Ugandan | 281 (98) | 84 (96) | 1.0 | 1.0 |
Ugandan | 5 (2) | 4 (5) | 0.37(0.098–1.4) | 0.6(0.1–2.4) |
Have chronic illnesses | ||||
Yes | 73 (26%) | 30 (34) | 1.0 | 1.0 |
No | 213 (75%) | 58 (66%) | 0.7(0.4–1.2) | 0.4(0.2–1.2) |
Currently on any long-term medication | ||||
Yes | 44 (24) | 62 (71) | 1.0 | 1.0 |
No | 142 (76) | 26 (30) | 0.4(0.2–0.8)* | 0.7(0.4–1.3) |
Ever had previous reactions to vaccinations | ||||
Yes | 17 (6) | 2 (2) | 1.0 | 1.0 |
No | 251 (88) | 79 (90) | 0.3(0.09–1.7) | 0.6(0.1–2.6) |
Not sure | 18 (6) | 7 (8) | 0.3(0.09–1.7) | 0.5(0.1–2.9) |
Usually have reactions to any medicine | ||||
Yes | 37 (13) | 10 (11) | 1.0 | 1.0 |
No | 249 (87) | 78 (89) | 0.9(0.4–1.8) | 0.8(0.3–1.7) |
Illness at the time you received the COVID-19 vaccine | ||||
Yes | 40 (14) | 7 (8) | 1.0 | 1.0 |
No | 246 (86) | 81 (92) | 1.6(0.6–3.9) | 1.0(0.4–3.1) |
Note: COR = Crude Odds Ratio, AOR = Adjusted Odds Ratio, * indicates p˂0.05 |
In our study, 77% of the participants reported having experienced an adverse event after receiving either dose of the vaccine. The most commonly experienced adverse events were injection site events, headache, and fever. Most adverse events had an onset within 3 days of receiving the vaccine and most events lasted between 1–3 days. In addition to that, those aged 20–29 years, 30–39 years and 40–49 years were more likely to develop adverse events than those aged ≥ 50 years. No serious adverse events were reported.
Most (77%) participants in our study revealed that they experienced an adverse event after either dose of the vaccine. As in most vaccines, an immune response is induced after AstraZeneca vaccination (18–20). These immune responses can lead to adverse events and these events occur in different persons differently (20, 21). In a prospective single-cohort study in Ethiopia among health workers to assess for adverse events after receiving the Oxford-AstraZeneca vaccine, 68% of the participants reported an adverse event (22). Despite a difference in the study designs, the results were similar. Similarly, in Togo, 72% of participants reported at least one adverse event after vaccination with AstraZeneca vaccine (ChAdOx1 nCoV-19 vaccine). However, in an online cross-sectional study assessing for self-reported adverse events in Bangladesh, 51% of the participants reported having experienced an adverse event after receiving a dose of the Oxford-AstraZeneca (Covishield) vaccine (23). This proportion might have been lower due to the nature of the study. In an online interview, a participant may not be able to freely express their symptoms. On the contrary, in a more engaging mode of communication such as phone interviews used in this study, participants may be led on to remember or recall some of the adverse events experienced. Furthermore, in an online interview, the participants may respond hurriedly thereby missing out on some adverse events experienced. We also compared proportions of individuals who experienced adverse events with other vaccines. An online cohort study in the United States analyzing with participant-reported adverse events after COVID-19 vaccination revealed that 65% reported an adverse effect after receiving Pfizer–BioNTech COVID-19 vaccine (BNT162b2) and 80% after Johnson % Johnson vaccine (24). A large-scale community-based study in the United Kingdom reported an even much lower rate of 33.7% (25). The variation may be due to the difference in study design and the heterogeneity of the populations. Some evidence has pointed towards ethnic differences and vulnerability to adverse events following vaccination (26).
We found that the most reported adverse events included injection site events, fever, headaches, and general body weakness. This is because the vaccine instructs the body immune system to react in certain ways including increases in blood flow more at the injection site, so more immune cells can circulate, and it raises the body temperature. This is consistent with other studies that reported similar reported adverse events among the population (24, 27–29). In most cases, adverse events are expected and people receiving the vaccine need to be sensitized. This helps to provide assurance and prepare them psychologically. Furthermore, health workers were also trained in managing adverse events as most are expected.
No serious adverse events were reported in our study. We believe this is due to short-lived, self-limiting symptoms that are mild or moderate in severity. Most adverse events were self-resolved with none requiring inpatient hospitalization, resulting in death, a permanent/persistent disability, or a congenital anomaly. A study in Ethiopia on adverse events among health care workers who received the Oxford/AstraZeneca vaccine noted similar results to our study. (22). Several studies have also reported no serious adverse events following vaccination with AstraZeneca (25, 30). In China, a meta-analysis of 12 different vaccines at phase 3 level of clinical trials revealed that the odds of serious adverse events following at least one dose of mRNA vaccines (AOR: 1.47; 95% CI: 0.65–3.3) was higher compared to those who received at least one dose of non-replicating viral vector vaccines (AOR: 0.76; 95% CI: 0.62–0.93) and inactivated vaccines(AOR: 0.79, 95% CI: 0.62–1.00) (31). However, the same study revealed that no solid evidence indicated that COVID-19 vaccines directly caused serious adverse events.
In our study, individuals aged 20–29 years, 30–39 years and 40–49 years were more likely to develop adverse events than those aged ≥ 50 years. Furthermore, the odds increased with decreasing age compared to those aged 50 years and above. This may be due to higher reactogenicity among younger people than their older. Younger individuals tend to have a more active immune system which wanes with increasing age (32). Similarly, several studies have noted increasing odds of adverse events among younger individuals following administration of AstraZeneca COVID-19 vaccine and other COVID-19 vaccines (22, 28, 30, 33). A comparative study among 3 different vaccines noted similar results (34). However, older individuals might report less adverse events as they often dismiss them as symptoms of old age. This has been shown in a non-COVID-19 related study (35). This implies that adverse events among elder individuals should be well-probed. Furthermore, older individuals and their caretakers where necessary should be sensitized to always seek medical advice where adverse events present.
Limitations of the study
Our study had some limitations. First, phone interviews were voluntarily reported by individuals; thus, they might not have been objective. Secondly, the data collected might also have been subjected to recall bias as a few weeks had passed for some participants before they were subjected to the questionnaire. This was addressed through proper explanation of the study purpose and detailed probing without leading the participants onto what to say during the interview. We also called back participants where we sought clarity was necessary. Use of a prospective study would alleviate this study limitation.
Most individuals experienced at least one adverse event after receiving either dose of the AstraZeneca COVID-19 vaccine. The most common adverse events were injection site events, headache and fever. No serious adverse events occurred. Younger age (< 50 years) was significantly associated with developing an adverse event compared to those aged 50 years and above. We recommend the use of the AstraZeneca COVID-19 vaccines in Uganda to help curb the spread of the COVID-19 infection based on its safety.
CDC, U.S Centers for Disease Control and Prevention
COVID-19, Coronavirus Disease 2019
MoH, Ministry of Health
SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2
UNEPI, Uganda National Expanded Program on Immunization
WHO, World Health Organization
Ethics approval and consent to participate
This assessment was in response to a public health problem and was therefore determined to be non-research. The MoH gave the directive to conduct this assessment. The Office of the Associate Director for Science, CDC/Uganda, also determined that this activity was not human subject research, and its primary intent was public health practice. Verbal informed consent in the local language was sought from respondents. They were informed that their participation was voluntary, and their refusal would not result in any negative consequences. To protect the confidentiality of the respondents, each was assigned a unique identifier which was used instead of their names.
Consent for publication
Not applicable.
Availability of data and materials
The datasets used and/or analysed during the current study belong to the Ministry of Health Uganda and are not publicly available. However, the data can be availed from the corresponding author upon reasonable request and with permission from the Ministry of health Uganda.
Competing interests
All authors declared that they have no competing interest.
Funding
This study was funded by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the U.S CDC Cooperative Agreement number GH001353–01 through Makerere University School of Public Health to the Uganda Public Health Fellowship Program, MoH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the US Centers for Disease Control and Prevention, the Department of Health and Human Services, Makerere University School of Public Health, or the MOH. The staff of the funding body provided technical guidance in the design of the study, ethical clearance and collection, analysis, and interpretation of data and in writing the manuscript.
Authors’ contributions
AK did the conceptualization of the study idea, data analysis, writing, and editing of the manuscript. JK, JI, FA, JA and EJN were involved in the conceptualisation of the study idea. FA, BK, DK, LB, JA, PN provided guidance in the writing and reviewing of the manuscript. LB and ARA were involved in the conceptualization of the study idea, writing, editing and reviewing of the manuscript. All authors read and approved the final manuscript.
Acknowledgements
We thank the respondents for their participation in the study. We also thank the District Health Teams of Kampala, Wakiso, and Mukono districts for the administrative clearance provided before conducting this study. We also thank the health workers at the different vaccination sites for cooperating with us during the study.