Risk factors for death due to COVID-19, in the state of Acre, Brazil, 2020: a retrospective cohort study
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Original
article Risk factors for death due to COVID-19, in the state of Acre,
Brazil, 2020: a retrospective cohort study
doi: 10.1590/S1679-49742021000300018
Patrícia Rezende do Prado¹ - orcid.org/0000-0002-3563-6602
Fernanda Raphael Escobar Gimenes² - orcid.org/0000-0002-5174-112X
Marcos Venicius Malveira de Lima³ - orcid.org/0000-0002-0332-2721
Virgilio Batista do Prado4 - orcid.org/0000-0003-0394-2143
Carolina Pontes Soares1 - orcid.org/0000-0002-9897-5863
Thatiana Lameira Maciel Amaral1 - orcid.org/0000-0002-9197-5633
¹Universidade Federal do Acre, Centro de Ciências da Saúde e do Desporto, Rio Branco, AC, Brazil
²Universidade de São Paulo, Escola de Enfermagem de Ribeirão Preto, Ribeirão Preto, SP, Brazil
³Secretaria de Estado de Saúde do Acre, Departamento de Vigilância Epidemiológica, Rio Branco, AC, Brazil
4
Secretaria de Estado de Saúde do Acre, Rio Branco, AC, Brazil
Abstract
Objective: To analyze risk factors for death in individuals with severe acute respiratory syndrome due to COVID-19.
Methods: This was a retrospective cohort study, comprised of adult individuals with COVID-19, from March to September 2020,
notified by the Epidemiological Surveillance System in the state of Acre, Brazil. Cox regression was used. Results: Among 57,700
individuals analyzed, the incidence was 2,765.4/100,000 inhabitants, and mortality was, 61.8/100,000 inhabitants. The risk
factors for death were: being male (HR=1.48 -95% CI 1.25;1.76), age ≥60 years (HR=10.64 -95% CI 8.84;12.81), symptom
of dyspnea (HR=4.20 -95% CI 3.44;5.12) and multimorbidity (HR=2.23 -95% CI 1.77;2.81), with emphasis on heart disease
and diabetes mellitus. 'Sore throat' and 'headache' were symptoms present in mild cases of COVID-19. Conclusion: Being
male, elderly, having heart disease, diabetes mellitus and dyspnea were characteristics associated with death due to COVID-19.
Keywords: Severe Acute Respiratory Syndrome; Coronavirus infections; Longitudinal studies; Risk Factors; Mortality.
Correspondence:
Thatiana Lameira Maciel Amaral - Universidade Federal do Acre, Centro de Ciências da Saúde e do Desporto, Campus
Universitário, BR 364, Km 4, Distrito Industrial, Rio Branco, AC, Brazil. CEP: 69920-900
Postcode: 500
E-mail: thatianalameira27@gmail.com
Epidemiol. Serv. Saude, Brasília, 30(3):e2020676, 2021 1Risk factors for death due to COVID-19
Introduction The aim of this research was to analyze the
epidemiological characteristics and risk factors for
Severe acute respiratory syndrome (SARS) due to death in individuals with SARS due to COVID-19 in the
COVID-19 (SARS due to COVID-19) is a viral respiratory state of Acre, Brazil, in 2020.
disease caused by a newly discovered coronavirus. It was
identified in Wuhan, Hubei Province, China, in December Methods
2019.1 The novel coronavirus has high transmissibility
and can cause severe acute respiratory syndrome and This was a retrospective longitudinal cohort study.
deaths. At the end of September, 2020, more than 32.7 Acre is located in the northern region of the country,
million COVID-19 cases and more than 1 million deaths in the Western Brazilian Amazon, borders Peru and
had been confirmed worldwide. The American Continent Bolivia, and had an estimated population of 881,935
was the hardest hit, with a number of cases exceeding people on July 1, 2019.5 The state has 380 health
16.2 million. Brazil was the second worst affected facilities, including centers and hospitals, distributed
country by COVID-19 in the Americas, with 4.8 million among 22 municipalities.6
confirmed cases and more than 143 million deaths.2 The study included all COVID-19 cases reported
in Acre by September 1, 2020. The first COVID-19
notification, in the state, occurred on March 15, 2020,
A lot of research is being conducted with the reported symptoms having started the day
in the search for practices based on before; the last case included in the study presented
scientific evidence. It is fundamental to the first symptoms four days before notification, on
contribute with epidemiological studies September 1, 2020. The time-zero of the cohort was
aimed at health promotion, disease defined by the date of onset of symptoms, and delta-
time (∆T) corresponded to the time between the date
prevention and hospital care planning, of symptom onset and outcome (cure or death) for
with identification of individuals cases with diagnostic confirmation of SARS due to
subject to risk factors for mortality. COVID-19. The follow-up time was 60 days, started
from the date of the first symptoms.
The pandemic has dramatically affected health Every case of SARS is compulsorily notified and typed
services. Many studies have been conducted in the individually on the Influenza Surveillance Information
quest for practices based on scientific evidence. It is System (SIVEP-Gripe), whose data were used on this
essential to contribute to epidemiological studies aimed notification system. On January 30, 2020, SARS due to
at health promotion, disease prevention and health COVID-19 was declared as a public health emergency of
care planning, with the identification of individuals international concern, by WHO, therefore the Ministry
subjected to risk factors for mortality.3 of Health, through Technical Note No. 20/2020-SAPS/
In this scenario, some risk factors for mortality GAB/MS, made it compulsory to notify cases in order
associated with SARS due to COVID-19 have been to enable longitudinal epidemiological investigation
suggested, such as severe lymphopenia, high levels of and formulation of health policies and strategies. This
C-reactive protein (correlated with severe hypoxemia), was the objective of this research.7
older age(≥60 years), male gender, race/skin color The diagnosis of COVID-19 was performed through
(non-white), lower socioeconomic level, presence of laboratory tests such as, molecular test (RT-PCR) or
comorbidities (e.g., diabetes mellitus, cardiovascular immunological test.
diseases, hypertension and cancer, presence of fever, SARS was defined by the concomitant presence
dyspnea, cough and immunocompromised status), as of four criteria: (i) fever, even if self-reported, (ii)
well as obesity and unhealthy lifestyle.4 However, such cough or sore throat, (iii) dyspnea or O2 saturation
factors may change depending on the characteristicsPatrícia Rezende do Prado et al. the public or private sector, throughout the national was used to analyze the continuous variables; and territory and according to the current legislation, categorical variables were described using absolute issued within 24 hours. (n) and relative (%) frequency. Pearson's chi-square The notification form of the e-SUS Epidemiological test and/or Fisher's exact test were used to compare Surveillance (e-SUS VE) contains the following independent variables with less than five occurrences. information related to individuals: notification number; Risk factors for death were analyzed using Cox Federative Unit and notifying municipality; Individual regression to estimate hazard ratio (HR) and their Taxpayer Registration Number (CPF); whether the respective 95% confidence intervals (95%CI). individual who was notified is a foreigner, health Multivariate analysis was performed using the variables professional or public security professional; date of that presented p
Risk factors for death due to COVID-19
Table 1 – Characterization of the individuals who got tested for COVID-19 (N=57,700) according to test results,
notified, Acre, Brazil 2020
Total Positive Negative
Variable p-valuea
N N % N %
Sexb Male 26,296 11,342 46.5 14,954 45.0Patrícia Rezende do Prado et al.
Continuation
Table 2 – Distribution of COVID-19 cases (n=24,389) according to municipality of residence, signs and
symptoms, and presence of multimorbidity, Acre, Brazil, 2020
Variable N %
Multimorbidity Yes 1,492 5.9
Heart disease 834 3.3
Diabetes mellitus 443 1.7
Chronic respiratory disease 186 0.7
Reported Morbidities Chronic kidney disease 103 0.7
Immunosuppression 173 0.7
Chromosomal disorder 61 0.2
High-risk pregnancy 63 0.2
Table 3 – Distribution of SARSa cases due to COVID-19 (n=18,987) according to epidemiological, clinical and
occurrence of death outcome due to the disease, Acre, Brazil, 2020
Total Death
Variable p-valueb
N N %
Sexc Male 8,905 333 3.7Risk factors for death due to COVID-19
Table 4 – Risk factors for death due to COVID-19a, Acre, Brazil, 2020
Adjustede
Variable Crude HRb 95%ICc p-valued 95%ICc p-valued
HRb
Sex Male 1.78 1.49;2.11Patrícia Rezende do Prado et al.
male, 60 years of age or older, dyspnea, presence of ICU and may progress to acute respiratory distress
multimorbidity, especially diabetes mellitus and heart syndrome (ARDS), with high mortality.4 In Rio Branco,
diseases; among the symptoms and signs related to better the prevalence of body mass index (BMI) above 25 kg/
prognosis, the presence of sore throat and headache, as m² is 48.4% among individuals aged 18 to 39 years, and
well as being a health professional stood out. 62.1% in the age group 40 to 59 years,15 which also
The pandemic began in Acre in mid-March 2020. At puts the younger population at risk, given that adipose
that moment, the emergence of COVID-19 in the state, tissue serves as a reservoir for the virus.16
represented an advantage for Acre by allowing more time It has been shown that health professionals,
to plan a regional Public Health response. In addition, especially nursing technicians, physicians and nurses
the city of Rio Branco has a specialized infectious disease are at greater risk of contracting COVID-19 because
laboratory, which allowed the identification of cases at they are at the forefront of health actions in the face
the beginning of the pandemic. Isolation measures, such of the pandemic. These professionals in their daily
as suspension of classes and restriction on non-essential work, risk their lives to save patients with SARS due
activities, were also implemented early, in order to to COVID-19, despite physical and mental exhaustion,
reduce the impact on the health system. However, these the concern and agony of having to make difficult
advantages and measures taken did not fully stop the decisions about patient screening process in health
spread of the disease, and deaths were inevitable. care services, the grief of losing patients, colleagues,
In this study, the profile of infected individuals shows friends, and also, the fear of transmitting the infection
that those at productive age are at higher risk of infection. to their families. The lack of personal protective
However, the higher mortality observed in individuals equipment (PPE) is also a concern17 and, despite the
aged 60 years or older corroborates the data obtained high infection rate, this study did not find an increased
in a study with 1,808 COVID 19 cases in the city of Rio de risk of mortality among health professionals. As if this
Janeiro, state capital of Rio de Janeiro, where, according were not enough, the high viral load in the most severe
to the researchers involved, people aged 30 to 59 years cases, puts the professionals responsible for their
were more frequent among the cases, while individuals care, among the groups at higher risk of infection,4
aged 60 to 89 years had a higher mortality rate.8 in addition to the asymptomatic and presymptomatic
Data from SouthKorea9 and Germany,10 in turn, transmission that accounted for, respectively, 51.7%18
showed a high incidence in the second decade of and 44.0%19 of the new infections.
life, an aspect to be considered equally, given that the Regarding symptomatic people, the main symptoms
German study suggested that this age group has played observed were: fever and cough; sore throat and
an important role in the spread of the epidemic, even dyspnea were also present among them. These findings
after the implementation of social distancing measures. corroborate a review of 65 articles, according to
In Italy, among Intensive Care Unit (ICU) cases, a mean which, other symptoms such as headache, diarrhea,
age of 63 years was observed, and only 13.0% were hemoptysis and runny nose, although less frequent,
less than 51 years old.11 were also identified; 20 and the most important
Elderly patients with COVID-19 are more likely to predictors of COVID-19 infection, loss of smell and
progress to severe disease,12 although recent studies loss of taste, were also identified in another study.21
point out that young people are not free of this Hyposmia is a prevalent symptom in individuals with
condition when they are obese. A study conducted in COVID-19, being more frequent in this disease than in
the United States showed that the prevalence of obesity other respiratory tract infections. It has been described
was nearly 40%, while in China, this condition was as a symptom with a high positive predictive value of
6.2%.13 In France, a significant association was found coronavirus infection (88.8%) and, also, as the initial
between prevalence of obesity and SARS due to severe symptom in up to 35% of the cases of the disease. It
COVID-19, suggesting that obesity might be a risk factor has been associated with less severe cases,3 as revealed
for severe disease progression and, consequently, a in the cohort of this study.
higher risk of ICU admission.14 Among the symptoms reported, regarding
Severe disease involves bilateral interstitial the presence of dyspnea, there was a statistical
pneumonia, which requires ventilatory support in the difference between those who died and those who
Epidemiol. Serv. Saude, Brasília, 30(3):e2020676, 2021 7Risk factors for death due to COVID-19
survived. Dyspnea is reported in severe cases, given underreported cases. However, the use of this database
that COVID-19 uses the angiotensin-converting allows to trace the profile of severe cases of SARS due to
enzyme 2 (ACE2) as a receptor, which is widely COVID-19, fundamental in times of pandemic.
found in lung, intestinal, kidney and blood vessel Another point to be considered is the self-report of
tissues. Moreover, this process results in the release multimorbidity, which may result in underreporting
of cytokines and consequent damage to pulmonary, and underestimation of the strength of association
renal and cardiac tissues.21 with adverse outcomes. It should be remembered
Regarding the presence of multimorbidity, it that self-report of chronic diseases is widely used,
was higher among individuals who died due to and that such information was obtained by health
COVID-19 in Acre. In New York, United States, a professionals. Further studies are needed to explore
study conducted with 5,700 hospitalized individuals the theme, using primary data sources and having a
showed that 88.0% had more than one morbidity, the longer follow-up time. Finally, the reduced number
most prevalent were: hypertension (56.6%), obesity of deaths resulted in wide confidence intervals,
(41.7%) and diabetes mellitus (33.8%).23 In China, requiring caution in the analysis of the data.
a study conducted with 1,590 hospitalized people The long-term follow-up stands out as the strong
showed that the most prevalent morbidities were point of this study, with assessment of 'cure' and
hypertension and diabetes, the hazard ratio (95%CI) 'death' outcomes. In addition, the study was conducted
was 1.79 (1.16;2.77) among individuals with at least in a state in the Northern region of Brazil, with a
one morbidity, and 2.59 (1.61;4.17) among those with population whose laboratory diagnosis for COVID
two or more morbidities.24 According to a Brazilian 19 and notification of the disease were performed
study conducted in the pandemic period up to the via the e-SUS VE/SIVEP-Gripe, being followed up for
21st Epidemiological Week of 2020, diabetes was also case closure and identification of health outcomes.
more prevalent in individuals hospitalized with SARS The choice of the type of study and the sample size, in
due to COVID-19, compared to the general population times of pandemic, reinforces its importance, insofar
of the country.25 The possible explanation for severe as work subsidizes knowledge about the reality of states
conditions in people with diabetes mellitus is due to that are far from the large urban centers in the country,
constant glucose recognition by C type lectin receptors, enabling the identification of regional risk factors for
generating greater inflammatory response.22 death due to COVID-19.
In a study with 1,139 cases and 11,390 controls Taking these results, it can be concluded that the
conducted in Madrid, Spain, researchers observed that study analyzed the epidemiological characteristics and
renin-angiotensin-aldosterone system inhibitors did risk factors for death in individuals diagnosed with
not increase the risk of SARS due to severe COVID-19, SARS due to COVID-19 in the state of Acre. Risk groups
and the discontinuity of treatment by patients was need special attention, especially the elderly, patients
discouraged. Furthermore, continuous monitoring with dyspnea and those with diabetes mellitus. Some
of these individuals was recommended because the symptoms were more frequent in mild cases of COVID-19
presence of cardiovascular diseases can aggravate and should be better elucidated in future studies.
pneumonia and may result in unfavorable outcomes.26
Among the limitations of this study, it is worth Authors’ contributions
mentioning the use of secondary data obtained from
the state epidemiological surveillance, which limited Prado PR, Gimenes FRE, Lima MVM and Soares
information detailing, especially about the presence or CP collaborated with the conception and design of
not of hypertension. It is suggested the inclusion of the the manuscript, data analysis and interpretation and
following variables: 'arterial hypertension', 'anosmia/ drafting the first version of the manuscript. Prado
hyposmia/dysgeusia/ageusia', 'myalgia', 'sore throat', VB and Amaral TLM collaborated with data analysis
'headache', 'runny nose' and 'diarrhea', in the e-SUS VE and interpretation, and critical reviewing of the
questionnaire, in order to better support future studies. manuscript. All authors have approved the final version
Other possible limitations of the study are (i) information of the manuscript and have declared themselves to
quality, dependent on the complete and correct be responsible for all aspects of the work, including
completion of the e-SUS VE notification form, and (ii) ensuring its accuracy and integrity.
8 Epidemiol. Serv. Saude, Brasília, 30(3):e2020676, 2021Patrícia Rezende do Prado et al.
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Received on 26/08/2020
Approved on 09/03/2021
Associate Editor: Bruno Pereira Nunes - orcid.org/0000-0002-4496-4122
Scientific Editor: Taís Freire Galvão - orcid.org/0000-0003-2072-4834
Editor-in-chief: Leila Posenato Garcia - orcid.org/0000-0003-1146-2641
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