Vaccine effectiveness in preventing deaths in people with severe acute respiratory syndrome due to COVID-19 in Blumenau, Brazil, 2021

ABSTRACT Objective to analyze the vaccine effectiveness in preventing deaths attributed to severe acute respiratory syndrome due to COVID-19 (SARS/COVID-19) in adults and the elderly, in Blumenau, state of Santa Catarina, Brazil, 2021. this was a population-based study conducted among individuals aged 20 years and older hospitalized with SARS/COVID-19; each death due to SARS/COVID-19 was considered a “case”, and every survivor was considered a “control”; the association between vaccination status and the outcome of “death” was estimated using logistic regression, and vaccine effectiveness was estimated as (1-OR)*100. The study included 1,756 cases of SARS/COVID-19 (59.2% male, mean age of 56 years, 50.4% with elementary education, 68.4% with comorbidities and 39.1% in intensive care), of whom 398 died (cases) and 1,358 survived (controls); vaccine effectiveness was 74% and 85% (20-59 years old) and 72% and 75% (≥ 60 years old), respectively, for those who were partially vaccinated and fully vaccinated. Conclusion vaccines proved to be effective in reducing case fatality ratio due to SARS/COVID-19 in individuals ≥ 20 years old.


INTRODUCTION
Severe acute respiratory syndrome (SARS) is a diffuse and inflammatory form of lung injury, characterized by poor oxygenation, pulmonary infiltrates, and acute onset.Due to its characteristics and the life-threatening risk this disorder poses, much has been discussed about the occurrence of SARS attributed to the novel circulating virus, SARS-CoV-2. 1 Cases of SARS-related hospitalization due to COVID-19 (SARS/COVID-19) reported in the Influenza Epidemiological Surveillance Information System (Sistema de Vigilância Epidemiológica da Gripe -SIVEP-Gripe) in Brazil in 2020 were 623,310, representing approximately 61.6% of all cases of SARS.In the following year, these cases increased by 16.7%; and 73.6% of SARS hospitalizations were due to COVID-19. 2 Globally, the number of deaths f rom the disease was estimated at 6.32 million as of June 2022. 3During the same period, Brazil recorded a total of 669,390 confirmed deaths due to COVID-19.In the Southern macro-region of the country, there were 105,346 deaths, and in the Southern state of Santa Catarina, specifically, 21,940 deaths were reported. 4The five national macro-regions presented different case fatality rates, 1 a factor likely supported by the diversity in the socioeconomic, cultural, and health characteristics of their populations. 5.7 Vaccination commenced in Brazil in January 2021, with the administration of the AstraZeneca/Fiocruz and Sinovac/Butantan vaccines; the Pfizer/Wyeth vaccine was included in May of the same year, and the Janssen vaccine in June, totaling four available vaccine products against the disease in the country. 4valuations of vaccine effectiveness are crucial not only to understand its effect on reducing infection and disease, but also to guide relevant public policies. 8Norway achieved a vaccine effectiveness in preventing deaths estimated at 46.9% after the first dose and 93.4% after the second dose. 9An analysis of clinical trials for vaccines, using the World Health Organization (WHO) Emergency Use Listing, estimated variable vaccine effectiveness, ranging from 90% to 99% after two doses, against the "death" outcome.These values were lower after a single dose: 70% to 90% against the same outcome. 10A meta-analysis of records from 51 studies estimated vaccine effectiveness in preventing deaths from COVID-19 at 58.4% for the partial vaccination status and 98.1% for the full vaccination status. 11In Brazil, the vaccination effectiveness for the outcome of "death" ranged from 35.3% for individuals aged 80 years and older, with a partial vaccination schedule, to 84.5% in the age group of 40 to 59 years with a full vaccination schedule. 7According to another Brazilian study, conducted with national hospitalization and vaccination data, vaccine effectiveness against death from COVID-19 with full vaccination schedule ranged from 57.7% to 89.9%, while with a single-dose schedule, effectiveness ranged from 35.3% to 61.8%. 12ta on vaccine effectiveness against COVID-19 in reducing the risk of death in people with specific health conditions are scarce, such as in the case of people hospitalized with SARS/ COVID-19 in Southern Brazil.
The objective of this study was to estimate vaccine effectiveness in reducing the risk of death in adults and older adults with SARS/COVID-19 living in the municipality of Blumenau, state of Santa Catarina, Brazil, in 2021.

METHODS
This was a population-based case-control study on SARS/COVID-19 cases with onset of symptoms occurring between January 1 and December 31, 2021, in residents of Blumenau, state of Santa Catarina.
The municipality of Blumenau, state of Santa Catarina, founded by German immigrants in the Médio Vale do Itajaí (26° 55' 08" South Latitude and 49° 03' 57" West Longitude), had an estimated population of 366,418 inhabitants and a gross domestic product (GDP) per capita of BRL 48,416.09 in 2021.Blumenau is an important industrial, technological and university hub in the state. 13rticipants and Data Sources All people with SARS/COVID-19 and a clinical picture of influenza-like illness who presented with dyspnea/respiratory distress or persistent chest pressure or oxygen saturation level below 95% on room air or blue discoloration of the lips or face, confirmed by RT-PCR test, 14 aged 20 years or older, living in Blumenau, with completed investigation and available in the SIVEP-Gripe database, were considered eligible for the study.The anonymized SIVEP-Gripe database was made available to researchers in April 2022.
"Cases" of SARS/COVID-19 resulting in death during the period established for the study were considered: n = 398.Based on the def inition of death due to SARS/COVID-19 described here, additional information related to deaths in the System's database was investigated by the Death Investigation Service of the Epidemiological Surveillance, in Blumenau, which checks the quality of the information recorded in Death Certif icates (DCs) by reviewing outpatient and/or hospital medical records.All cases of SARS/COVID-19 that survived during the same study period were defined as "controls": n = 1,360.Taking into consideration a first-dose vaccine coverage of 30% for 398 cases, and 40% for 1,358 controls, a study power of 97% was estimated for an odds ratio (OR) of 0.63 and a 95% confidence interval (95%CI).Furthermore, considering vaccine coverage with two doses or a single dose of 20% for 398 cases, and 30% for 1,358 controls, a study power of 98% was estimated for an OR = 0.58 and 95%CI (Figure 1).
Information on vaccination status (exposure variable) was reviewed at the Immunization Coordination of the Municipal Health Department of Blumenau.

Exposure Variable
Regarding vaccination status, participants were classif ied as "unvaccinated", "partially vaccinated" (received 1 dose) or "fully vaccinated" (received one dose of the single-shot Janssen vaccine, or received two doses of the others), regardless of vaccine type, brand or batch.In Blumenau, the first doses of vaccine were administered on January 20, 2021.Booster doses were not taken into account, as they only began from epidemiological week 37 of 2021, in the municipality.

Statistical methods
The variables were examined according to the type of distribution: continuous variables were presented by measures of central tendency and dispersion; and categorical variables, by absolute and relative frequencies.As these are secondary data, the presence of incompleteness was checked, and variables with more than 10% incompleteness were excluded.
The comparison of means was performed using Student's t-test, and the comparison of proportions, using Pearson's chi-square test.The association between vaccination status (partial; complete) and the occurrence of death, both overall and by age group, was estimated by means of odds ratio (OR) and 95%CI obtained using unconditional logistic regression, crude and adjusted for sex, age, schooling, place of residence, number of comorbidities, and previous influenza vaccination.All study variables with a p-value < 0.20 in the univariate analysis were included in the adjusted models.
Vaccine effectiveness was estimated using the following formula: 1 -OR of vaccination between cases and controls *100. 16Model adjustment was estimated using the Hosmer-Lemeshow test.Statistical analyses were performed using the Stata 11.2.A p-value < 0.05 was considered statistically significant.

Ethical aspects
This study is part of the research project entitled "COVID-19 vaccine effectiveness in Blumenau, state of Santa Catarina: a casecontrol study", approved by the Human Research Ethics Committee (HREC), of the Fundação Universidade Regional de Blumenau (FURB), on August 7, 2021: Certif icate of Submission for Ethical Appraisal (CAAE) No. 46513121.5.0000.5370;Opinion No. 4,891,763.Due to the use of secondary data, the project was exempt from requiring the participants to sign the Free and Informed Consent Form (FICF).

RESULTS
There were 2,570 cases of SARS in residents of the municipality of Blumenau in 2021, and among them, 1,829 were confirmed as COVID-19 through RT-PCR test or antigen test.Of these, 1,756 people aged 20 years or older took part in the study, of whom 398 died from SARS/COVID-19 (cases) and 1,358 survived (controls).Figure 1 shows the participant selection flowchart.
Regarding data completeness for study variables, sex, age group, comorbidities, and COVID -19 vaccination status had 100% completeness.The percentage of incompleteness for the other variables was 5.2% for schooling, 4.2% for previous influenza vaccination, 2.5% for number of comorbidities,

ORIGINAL ARTICLE
Vaccine effectiveness in preventing deaths due to SARS-COVID-19 2% for race/skin color, 1.5% for ICU admission, 0.5% for place of residence, and 0.2% for deaths.
Table 1 shows some of the clinical and epidemiological characteristics of the cases and controls.There was no statistically significant difference in sex and race/skin color between cases and controls.The mean age was higher among cases (66.3 versus 53.1 years; p-value < 0.001).In addition, a higher proportion of people with lower level of education, three or more comorbidities, without previous influenza vaccination and those who required ICU admission were observed among cases.As for associated comorbidities/risk factors, chronic cardiovascular disease (47.7%), obesity (35.6%), diabetes mellitus (31.9%), other chronic lung diseases, chronic kidney disease (4,2%), asthma (4,2%), chronic neurological disorders (3.6%), immunodeficiency (3.0%), chronic liver disease (0.8%), chronic hematological disorders (0.5%), being a puerperal woman (0.3%) and Down syndrome (0.1%) (data not shown in the table).Vaccination coverage, both for the first dose and for the second dose or single dose, was higher in the control group.
Table 2 shows the results of the crude and adjusted analyses of the association between vaccination status and death, by dose and age group, in people with SARS.A higher chance of protection against death was found among vaccinated people, both among those who received one dose and those who received two doses.

DISCUSSION
Vaccination, adjusted for confounding variables, proved to be effective in reducing deaths from SARS/COVID-19.Even in populations aged 60 years or older and with incomplete vaccination status, vaccine effectiveness was above 70%.
When characterizing the study population in the clinical and epidemiological terms, it could be seen that the majority of people with SARS/COVID-19 were male, a finding similar to that of other national [17][18][19] and international studies. 20The age group of 20 to 59 years was the most affected by SARS/COVID-19, consistent with findings from a national study. 21However, SARS/COVID-19 hospitalizations were related to the oldest age groups, especially those aged 60 years and older. 18,19 this sample f rom Blumenau, SARS/ COVID-19 cases had a higher f requency of comorbidities when compared to controls.2][23] The most prevalent comorbidities were cardiovascular disease, obesity, diabetes mellitus, and other chronic lung diseases unrelated to the current COVID-19 disease.The frequency of these comorbidities in cases of SARS-COVID-19 decreased significantly when compared to cases with mild COVID-19. 24It is also noteworthy that just under half of the individuals hospitalized due to SARS/COVID-19 required ICU admissions, a figure close to the national findings. 23en examining the profile of cases that progressed to death due to SARS/COVID-19, some peculiarities were observed, including the oldest age group (between 60 and 79 years), lower level of schooling (illiterate or with an education level up to elementary school) and the presence of comorbidities.The association between the risk of negative outcomes of COVID-19 and increasing age was identified at the beginning of the pandemic, 24,25 although it has not been extensively explored in the context of SARS/COVID-19.9][20][21][22][23] This can be explained, at least in part, by expressing educational and cultural characteristics associated with knowledge about the disease and its complications, as well

ORIGINAL ARTICLE
Vaccine effectiveness in preventing deaths due to SARS-COVID-19  as by representing an approximation of worse economic conditions.I n t h i s s t u d y, va cc i n e e f fe c t i ve n e s s against SARS/COVID-19 showed a greater protective effect in the youngest age group of the sample, f rom 20 to 59 years old, and among those with the complete vaccination schedule, i.e., two doses or a single dose.In the state of Rio Grande do Sul, the State Center for Health Surveillance found 58% effectiveness of partial COVID-19 vaccination in the occurrence of SARS/COVID-19 among the elderly; and over 90% in the population with a complete vaccination schedule, among those aged 20 to 59 years. 26Consistent with the f indings of this study, it could be seen that the estimates of vaccine effectiveness in preventing deaths are higher in the younger age group. 7Such differences in vaccine effectiveness are likely attributed to the different vaccination schedules (the complete vaccination schedule provides greater stimulus to the immune response) and the different age groups [in older adults, the immunosenescence process (changes in the immune system caused by aging), combined with the presence of comorbidities, hinders the immune response]. 9,27 the study used secondary data, it was subject to information bias, given that the data may contain diagnostic errors, failures, and incompleteness in the records.In addition, the effectiveness by type of vaccine administered was not analyzed, since this information was not available in the database used at the time of the study.Nevertheless, this study depicted real-world vaccine effectiveness and its use conditions.
It can be concluded that vaccination against COVID-19 proved to be effective in reducing the risk of death among people aged 20

Figure 2
Figure 2 presents the vaccine effectiveness in reducing deaths among people with SARS/ COVID-19.

Figure 2 -
Figure 2 -Vaccine effectiveness in reducing deaths in people with severe acute respiratory syndrome due to COVID-19 (SARS/COVID-19), by dose and age group, Blumenau, state of Santa Catarina, Brazil, 2021

,358 Figure 1 -Flowchart of the selection of study participants, based on cases of severe acute respiratory syndrome due to COVID-19 (SARS/COVID-19), with onset of symptoms occurring between January 1 and December 31, in residents of the municipality of Blumenau, state of Santa Catarina, Brazil, 2021
c) self-repor ted race/skin color (White; non-White); f) presence and number of comorbidities; g) t y p e o f c o m o r b i d i t y / r i s k f a c t o r (Down syndrome; diabetes mellitus;