The incorporation of vaccines into the arsenal of control measures, at the end of 2020, changed the course of the COVID-19 pandemic. A reduction in the incidence of the disease was observed, particularly in severe cases, hospitalizations and deaths.

An unprecedented effort in history by the academic community, research funding agencies, health care services, governments and the pharmaceutical industry, enabled the short-term development of safe and effective vaccines against SARS-CoV-2. The consultation of the WHO SARS-CoV-2 vaccine landscape demonstrates the strength of this effort. Almost 400 vaccine candidates were in different stages of development as of March 2023, of which 180 had reached the clinical investigation phase, and more than thirty were already on the market.1 Several platforms have been used in their development and manufacturing, some new, such as mRNA vaccines, viral vector vaccines, and protein subunit vaccines, as well as other technologies already widely used in vaccines’ manufacturing for other infectious agents, such as inactivated vaccines.

CoronaVac, an adjuvanted inactivated virus vaccine, developed by the pharmaceutical company SINOVAC, in partnership with the Butantan Institute, was the first vaccine available in Brazil. Phase 3 trials demonstrated its safety, and an efficacy in preventing symptomatic disease caused by SARS-CoV-2 from 50.7 % (95 % CI 36.0–62.0 %) in Brazil,2 to 83.5 % (95 % CI 65.4–92.1 %) in Turkey.3 Safety and efficacy data are fundamental for the analysis of a product by regulatory agencies, which decide on authorization for the commercialization and use of the vaccine, but it is data on the effectiveness of the vaccine that allow the evaluation of the product's performance in real life.

The vaccination campaign against COVID-19 in Brazil began in January 2021. As of the second half of the year, studies on the effectiveness of the vaccination program began to be published. The vast majority of them used data routinely collected by national health information systems, specifically the mandatory reporting diseases system and the vaccination registry. Although they are able to provide relevant information, effectiveness studies with secondary data are limited in terms of the completeness and quality of the data, and usually demand probabilistic linking of database records. In order to overcome these limitations, the present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing symptomatic disease with virological confirmation by SARS-CoV-2, as well as COVID-19 moderate and severe cases.

A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 with virological confirmation, and controls were those whose test was negative for SARS-CoV-2.

Cases and controls were obtained at primary health care and emergency care clinics or from COVID-19 surveillance database with the onset symptoms registered from March to November 2021 from two municipalities located in the state of São Paulo, Brazil: Campinas (population 1,223,237 in 2021) and Araraquara (population 240,542 in 2021).6

The eligibility criteria were: being a clinically suspected COVID-19 case, according to the Brazilian Ministry of Health definition (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders)4; having performed the RT-PCR test with a sample collected within 7 days of the onset of symptoms; being 18 years or older, and having had the chance to receive two doses of the CoronaVac vaccine in the basic scheme, in accordance with the vaccination strategy of the municipality of residence. The exclusion criteria were to have a contraindication to the use of any vaccine against COVID-19; and having received any COVID-19 vaccine other than CoronaVac in the basic scheme.

A total of 2981 potential participants were screened for eligibility, of which 2163 were actually included, being 493 cases and 1670 controls (Fig. 1).

Fig. 1.

Participants flowchart.

(0.22MB).

Cases were older and less educated than controls (Table 1). They also were more likely to have had contact with someone with suspected or confirmed COVID-19 in the two weeks before the onset of symptoms (Table 2). Regarding their vaccine status, cases and controls were classified as unvaccinated, vaccinated with a complete schedule, or vaccinated with an incomplete schedule (Table 2). For vaccinated participants, the median interval between the second dose and the onset of symptoms was 110 days (Results are not show).

Cases were more likely to refer chronic comorbidities than controls: diabetes mellitus, hypertension, heart disease and pulmonary disease (Table S1).

In the univariate analysis, the variables that were significantly associated with the odds of being a case were age, the educational level, any previous comorbidity, and the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset (Tables 1, 2 and S1). Regarding the clinical severity classification, the vast majority of controls were classified as mild. As for COVID-19 cases, almost a quarter of them were classified as moderate/severe (Table 2 and S2).

In the multivariate logistic regression analysis, the age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level remained in the model, being independently associated with the outcome (Table 3). Finally, the Adjusted Vaccine Effectiveness (AVE) for symptomatic virologically confirmed COVID-19 was 38.9 % (95 % CI 5.9 %‒60.4 %) (Table 4).

The multivariate model was adjusted comparing moderate/severe cases to the mild ones. In this analysis, vaccination with complete schedule was independently associated with severity, along with age, educational level, contact with a suspected or confirmed case in the 14 days before symptoms onset, and reporting any comorbidity (Table 5). Adjusted vaccine effectiveness for moderate/severe cases was 91.4 % (95 % CI 75.6 %‒96.9 %) with a complete schedule (Table 4).

In this test-negative case-control study, effectiveness of CoronaVac in the prevention of symptomatic virologically confirmed COVID-19 was 39 %. These figures are in line with the results of other CoronaVac effectiveness studies. In the State of São Paulo, Brazil, in early 2021, effectiveness of CoronaVac among older adults was estimated in 46.8 % (95 % CI 38.7–53.8 %).7 In Hong Kong, the effectiveness of CoronaVac in the prevention of mild to moderate disease among adults from 20 to 59 years of age was 25.1 % (95 % CI 14.7–34.3 %).8 In Guangdong, China, effectiveness against infection was 60.4 % (95 % CI 31.8–88.9 %) during an outbreak of the Delta variant.9 However, in Chile, the effectiveness of CoronaVac in the prevention of symptomatic virologically confirmed COVID-19 was higher (VE = 65.9 %; 95 % CI 65.2–66.6 %) in a study conducted in a short term after the vaccination campaign.10

Regarding moderate/severe disease, a high effectiveness was observed. Our result is consistent with the results of other studies. In a large study carried out with secondary data in Brazil, the effectiveness of CoronaVac for hospitalization due to COVID-19 was 95.6 % (95 % CI 82.4–99.9 %).11 Among older adults in the State of São Paulo, Brazil, effectiveness was 77.6 % against hospitalization, and 83.9 % against death.7 In Chile, effectiveness was 87.5 %, 90.3 % and 86.3 % against hospitalization, ICU admission, and death, respectively [10] while in Hong Kong, effectiveness of Coronavac in the prevention of severe disease and death was 69.9 %.8

Effectiveness estimates are usually lower than efficacy figures obtained in clinical trials. Efficacy of CoronaVac was 50.7 % in a study among frontline healthcare workers in Brazil (Palácios et al.); 65.3 % and 83.5 % among healthy adults from 18 to 59 years of age in Indonesia and Turkey, respectively.3,12 It has been documented that SARS-CoV-2 vaccines protection wanes over time.13 A study carried out in China showed that the effectiveness of CoronaVac against symptomatic infection decreased after six months, but remained high for serious outcomes, such as death.14

When interpreting and comparing different effectiveness studies, it is important to consider some aspects that may influence their results. The design of the study, the analyzed outcomes, the population or population subgroup included the period when the study was carried out, in relation to the evolution of the epidemic, as well as the follow-up time of the participants, should be taken into account. The present study was conducted right after the rollout of SARS-CoV-2 vaccines in Brazil, in early 2021. During the first trimester of 2021 Brazil experienced a large increase in the number of new COVID-19 cases and deaths, corresponding to the emergence of the Gamma variant.15 With time and the increase in vaccination coverage, the Gamma variant waned, and there was a drop in the number of cases in the second half of the year, when the field work of our prospective phase begun, and the predominant variant shifted to Delta. Older adults were the among the priority groups for vaccination, being the first ones to be vaccinated. This may have reduced the incidence and severity of cases among the population over 60 years of age, which accounted for just 20 % of study participants (data not shown). Regarding the follow-up time, among the participants for whom this variable can be computed, it was between 15 and 16 weeks. The study design in the prospective phase allowed the inclusion of a large proportion of eligible patients, the number of refusals was minimal.

In addition to the limitations arising from the observational design, our study has some others that deserve to be mentioned. Our sample size was small, not allowing us to estimate effectiveness by age group, especially for the older population. The number of severe cases was also small, and there was a higher concentration of deaths among subjects identified from the surveillance database, as the IRB exempted us from obtaining the informed consent form for their inclusion in the study.

In summary, the study demonstrated the high effectiveness of CoronaVac in preventing moderate and severe cases of COVID-19. Its effectiveness against virologically confirmed symptomatic infection was within expectations, similar to that observed in other studies, in the pre-Omicron period. The inactivated vaccine platform is very well known, representing lower costs than other COVID-19 vaccine's platforms, and has a high potential and capability for the national manufacturing to provide sustainable supply to the Ministry of Health.