WORK HOURS AS A RISK FACTOR FOR SARS-COV-2 INFECTIONS: CARDIOMETABOLIC AND SLEEP CHARACTERISTICS IN ROTATING SHIFT WORKERS - SLEEP ...

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1   Work hours as a risk factor for SARS-CoV-2 infections
    SHORT COMMUNICATIONS

    Work hours as a risk factor for SARS-CoV-2 infections:
    cardiometabolic and sleep characteristics in rotating shift workers

    Raiza Aranha Nascimento1                      ABSTRACT
    Virgínia Capistrano Fajardo2
    Luiz Antônio Alves Menezes Junior3*           Objective: This study aims to describe the health characteristics of rotating shift mining workers
    Pedro Henrique Marques Mendonça4              that may be related to a worse course scenario for COVID-19, according to literature data. Methods:
    Maria Cristina Veiga Aranha Nascimento5       Is a cross-sectional from three studies with 1478 shift workers. Social, demographic, clinical, and
    Pedro Marques Oliveira Tristão6               biochemical variables were analyzed. Risk factors for COVID-19 analyzed: hyperglycemia, altered
    Fernando Luiz Pereira Oliveira7               blood pressure, dyslipidemia, hypovitaminosis D, obesity, presence of pre-existing cardiovascular
    Raimundo Marques Nascimento Neto5             diseases, and smokers. Results: Evaluating the grouped risk factors for an unfavorable evolution of
                                                  COVID-19 most workers (91.0%) presented at least one risk factor. Discussion: With coronavirus
                                                  in pandemic circulation, we noticed that mineworkers are in a vulnerable position. Their exposure to
                                                  occupational risk factors, to the shift system, which directly affects sleep and negatively influences
                                                  immunity, added to the conditions of favorable transmissibility by the flow of people from the mines
    1
     Belo Horizonte City Hall, Endocrinologist    leads us to believe in their greater susceptibility to acquiring the most serious forms of the disease.
    - Belo Horizonte - Minas Gerais - Brazil
    2
     Sciences Applied to Adult Health             Keywords: Coronavirus Infections; Betacoronavirus; Sleep Deprivation; Circadian Rhythm; Mining.
    Care Postgraduate Program, School of
    Medicine, Federal University of Minas
    Gerais, Belo Horizonte
    3
     Postgraduate Program in Health and
    Nutrition, Federal of University Ouro
    Preto - Ouro Preto - Minas Gerais - Brazil.
    4
     Postgraduate Program in Infectology and
    Tropical Medicine, Federal of University
    Minas Gerais - Belo Horizonte - Minas
    Gerais - Brazil.
    5
     Federal of University Ouro Preto, School
    of Medicine - Ouro Preto - Minas Gerais
    - Brazil.
    6
     Belo Horizonte City Hall, Cardiologist -
    Ouro Preto - Minas Gerais - Brazil.
    7
     Federal of University Ouro Preto,
    Institute of Exact and Biological Sciences
    - Ouro Preto - Minas Gerais - Brazil.

    *Corresponding author:
    Luiz Antônio Alves Menezes Junior
    E-mail: alves.luizantonio@gmail.com

    Received: March 8, 2021;
    Accepted: April 19, 2021.

    DOI: 10.5935/1984-0063.20210013

    Sleep Sci. 2021; Ahead of Print
Nascimento RA, et al.   2
INTRODUCTION                                                             was carried out in 2012, with 516 shift workers from four mines
         In late 2019, a new coronavirus (SARS-CoV-2) was                in the Iron Quadrangle region. A systematic sampling process
identified as causing pneumonia. Subsequently, the infection spread      was carried out to assess vitamin D (25 (OH) D), (n=391).
rapidly around the world, resulting in a pandemic. So far, the only      There were losses due to incomplete data, abstaining from the
effective measure to stop the spread of the virus is social isolation,   answers to the questionnaire, or due to not having collected
which has had major impacts on the global economy. In this context,      blood (n=33). Totaling 358 individuals evaluated; b) the second
in Brazil, mining activities were defined by the federal government      study was carried out in 2015 with shift workers from another
as essential, that is, they maintained their activities during the       mine in the Iron Quadrangle region. The population of shift
COVID-19 pandemic. The Movement for Popular Sovereignty                  workers with the position of operators was invited to participate
in Mining (MAM) crossed data from the National Mining Agency             (n=275). Of these, there were losses due to non-participation
(ANM) with those of the health secretariat of the state of Pará          due to refusal, vacations, leave and time off (n=17); and
and concluded that the municipalities where there are large mining       incomplete data for not having answered the questionnaire or
projects in this state are the most affected by COVID- 191.              for not having collected blood (n=66). Totaling 192 individuals
         Shift workers are subjected to changes in the circadian         evaluated; c) the third study was carried out in 2018 on shift
cycle resulting in insufficient sleep syndrome (SSI) defined as a        workers (operators and non-operators) in the southern region
decreased quantity or impaired quality of sleep. The American            of Pará. Of these, there were losses due to incomplete data,
Heart Association (AHA) has recognized sleep deprivation as a            for not having answered the questionnaire or for not having
cardiovascular risk factor since 2016. It is associated with central     collected blood (n=169). Totaling 932 individuals evaluated.
obesity, high fasting blood glucose, hypertension (HT), metabolic        In all three studies, the population of shift workers with the
syndrome, sleep disorders, and immunological changes2. All of            position of operators was invited to participate. In this study,
these factors have been well established as risk factors for the         1,482 shift workers were analyzed.
unfavorable evolution of COVID-19. As found by Peters et                         Participants of cross-sectional studies carried out in
al. (2021)3 evaluating 502,493 individuals, found that increased         2012, 2015 had a rotating shift schedule (4x1) of the six hours
waist circumference was associated with a higher risk of death           of work, followed by 12 hours of rest. After finishing the
from COVID-19 (HR: 1.36; 95% CI = 1.18-1.57). Suggesting                 weekly four-shift cycle, they receive one day off. Participants of
that abdominal obesity appears to be a risk in COVID-193. High           the cross-sectional study carried out in 2018 had a rotating shift
glucose levels are also considered risk factors for COVID-19.            schedule of (5x2) of the eight hours of work, followed by 24
Dennis et al. (2021)4 evaluating 19,256 patients admitted to             hours of rest. After finishing the weekly five-shift cycle, they
hospital in England with COVID-19, found that patients with              receive two days off.
type 2 diabetes had a higher risk of death (HR: 1.23; 95% CI =
                                                                         Data collect
1.14-1.32). Another important factor to be considered is that
SSI impairs immunity, making its carriers more susceptible to                    In all studies, data collection was performed face-to-
viral infections such as the common flu5.                                face by teams trained to administer the questionnaires, measure
         Mining shift workers may not initially be classified as at      anthropometric data, and collect biological samples.
risk for severe forms of COVID-19 because they are young and                     The social, demographic, and economic variables
supposedly healthy individuals. However, specific characteristics        evaluated were: sex, age, self-reported skin color, and scholarly.
of this population call the attention of the scientific community        Age was categorized as 20-29 years, 30-39 years, 40-49 years, 50-
and must be carefully evaluated. Given a large number of                 59 years, and 60 years or more; the self-declared skin color was
workers with comorbidities associated with the severe form of            categorized as White, Black, and Brown-Skinned (Black, Mulatto,
COVID-19 and the maintenance of their activities during the              Mixed or Mixed-Race), and others (Yellow or Indigenous);
pandemic, we believe it is imperative to warn about the potential        scholarly was categorized into up to 1st degree complete, 2nd
risks that this represents. This data can be useful for damage           degree complete, technician, graduated, and postgraduate.
containment strategies for current and future pandemics.                         The clinical evaluation was carried out employing a
         The study aims to describe the health characteristics of        questionnaire about pre-existing diseases, use of medication,
rotating shift-mining workers that may be related to a worse             and smoking habits; and by measuring blood pressure. The pre-
course scenario for COVID-19, according to literature data.              existing diseases evaluated were: hypertension (HT), diabetes
                                                                         mellitus (DM), dyslipidemia, cardiovascular diseases, respiratory
MATERIAL AND METHODS                                                     diseases, and chronic kidney disease. The drugs evaluated
                                                                         were: antihypertensive, lipid-lowering, hypoglycemic agents,
Study design and population                                              and antiplatelet agents. Among the antihypertensive drugs,
       A cross-sectional study carried out with a population             the following classes were evaluated: angiotensin-converting
of shift workers from an iron ore extraction company in two              enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB),
locations, in the Iron Quadrangle region, Minas Gerais, and the          thiazide diuretics, beta-blockers, calcium channel blocker, and
south of the state of Pará. The data analyzed comes from three           aldosterone receptor blocker. The smoking habit was categorized
studies carried out with workers in rotating shifts: a) the first        as a non-smoker, ex-smoker, and smoker. Blood pressure was

                                                                                                             Sleep Sci. 2021; Ahead of Print
3   Work hours as a risk factor for SARS-CoV-2 infections

    measured in triplicate with a digital semi-automatic device.       (BMI ≥30kg/m2); f) presence of pre-existing cardiovascular
    The measurement protocol followed the recommendations              diseases; g) smoker (smokers and ex-smokers).
    of the Brazilian Society of Cardiology in force in the year               Categorical data are presented as absolute (n) and relative
    of data collection. Blood pressure was classified as normal        (%) frequencies. Continuous data presented as median and 50th
    (systolic blood pressure [SBP] ≤120mmHg and diastolic [DBP]        and 75th percentiles (P25-P75), minimum and maximum. The
    ≤80mmHg), prehypertension (SBP 121-139mmHg or DBP                  Shapiro-Wilk test was used to verify the normality of the data.
    81-89mmHg), stage 1 hypertension (SBP 140-159mmHg or               The missing data were reported in each table and were less than
    DBP 90-99mmHg), stage 2 hypertension (SBP 160-179mmHg              5%. Descriptive analysis was performed using the Stata SE
    or DBP 100-109mmHg), and stage 3 hypertension (SBP                 software, version 15.0 (StataCorp, College Station, TX, U.S.).
    ≥180mmHg or DBP ≥110mmHg)6.                                               The protocol of the three studies was approved
             The evaluation of the biochemical profile was performed   by the human research ethics committee of the Federal
    by analysis of the lipid profile, vitamin D, and glycemia. In      University of Ouro Preto (2012: CAAE No.: 0018.0.238.00-
    the first two years, blood samples were collected after a 10-      11; 2015 CAAE No.: 39682014.7.0000.5150; 2018: CAAE No.:
    hour fast and in 2018 it was collected without a previous fast.    93760618.5.0000.5150). All participants signed an informed
    Total cholesterol (TC), high-density lipoprotein-cholesterol       consent form.
    (HDL), and triglycerides (TG), which were determined by
    the enzymatic-colorimetric method. Low-density lipoprotein-        RESULTS
    cholesterol (LDL) was calculated using Friedewald’s Equation               In a total of 1,482 shift workers mostly were men
    (1972) when the concentrations of TG were
Nascimento RA, et al.      4
Table 2. Characterization of the main risk factors for COVID-19 of the 1482 mining shift workers
 Parameters                  Classification                                Cutoff                                                                  Total (n= 1482)
 Vitamin D                   Sufficient                                    > 20 ng/mL                                                                 1204 (78.8)
                             Hypovitaminosis D                             ≤ 20 ng/mL                                                                  278 (18.2)
 Diabetes Mellitus           Pre-existing disease                                                                                                       43 (2.9)
                             Use of anti-glycemic medication                                                                                            23 (1.6)
 Glycemia                    Normoglycemia                                 Fasting glucose  43 cm Women: > 38 cm                              114 (7.7)

                                                                                                                                     Sleep Sci. 2021; Ahead of Print
5   Work hours as a risk factor for SARS-CoV-2 infections

    Table 4. Risk factors for COVID-19 of the 1482 workers on mining shifts.                is a highly active organ that interferes with the body’s immune,
     Parameters                              Classification          Total (n= 1482)        endocrine, and metabolic homeostasis13. To date, we have no
                                                Diabetes                463 (31,5)          direct evidence that SARS-CoV-2 infects adipose tissue, although
                                             Blood pressure             561 (37.9)
                                                                                            type 2 ACE, a receptor used by the virus to enter the cell, is
                                                                                            present in adipose cells13.
                                              Dyslipidemia              1155 (77.9)
                                                                                                     Recent studies have shown that interleukin 6 (IL-6) is
     Risk factors for COVID-19            Hypovitaminosis D             293 (19.8)
                                                                                            a strong independent predictor of mortality in patients with
                                                 Obesity                313 (21.1)
                                                                                            COVID-19. Associated with this we know that adipose tissue is
                                        Cardiovascular diseases          12 (0.8)
                                                                                            the major source of IL-6 and its receptor in the human body.
                                                 Smoker                 232 (15.7)
                                                                                            The hypothesis arises that adipose tissue may be a source of IL-6
                                             No risk factor              132 (9.0)          activation and a trigger for the inflammatory cascade13. In addition
                                              1 risk factor             394 (26.8)          to being overweight, lipid location plays an important role in the
                                              2 risk factors            464 (31.5)          development of sleep-disordered breathing. The deposition of
     Risk factors for COVID-19
     grouped
                                              3 risk factors            292 (19.9)          fat in the neck and waist is the most relevant to a greater risk
                                              4 risk factors             145 (9.9)          of sleep-disordered breathing. There are several mechanisms,
                                              5 risk factors             41 (2.8)           greater deposition of fat in the abdominal region predisposes to
                                              6 risk factors              2 (0.1)           reduced diaphragm activity and the volume of inspired air. As
    Diabetes: altered blood glucose (pre-diabetes or diabetes) or use of anti-glycemic
                                                                                            well, due to the waist circumference reflecting the accumulation
    drugs; Blood pressure: altered blood pressure (stage 1 or higher hypertension) or use   of visceral fat, much more related to sleep apnea than other
    of antihypertensive drugs; Dyslipidemia: TC ≥ 190 mg / dL, or HDL ≤ 40 mg / dL,         forms of obesity. Also, there is a decrease in the caliber of the
    or LDL ≥ 130 mg / dL, or TG ≥ 150 mg / dL or use of lipid-lowering drugs (with or
    without fasting); Hypovitaminosis D: 25 (OH) D < 20 ng / mL; Obesity: BMI ≥ 30 kg       upper airways, caused by excess fat in the neck region. These and
    / m2; Cardiovascular diseases: pre-existing diseases; Smoker: smoker or ex-smoker.      other factors contribute to the fact that excess adiposity favors an
                                                                                            increased risk for respiratory sleep disorders9.
    that can contribute to a worse COVID-19 infection outcome                                        Hypovitaminosis D (
Nascimento RA, et al.   6
D reduces the production of reactive oxygen species and                  we observed an alarmingly higher prevalence of HT among
proinflammatory mediators contributing to endothelial function14.        shift workers when compared to the population of the same age
         A retrospective observational study of de-identified tests      and gender. Also, of the antihypertensive drugs used, the most
performed at a national clinical laboratory with 191,779 patients        reported were ARB (43.7%), ACE inhibitors (27.6%), thiazide
demonstrated an inverse relationship between circulating 25(OH)D         diuretics (24.1%), and calcium channel blockers (23.0%).
levels and SARS-CoV-2 positivity (R-squared=0.96). Patients who          However, there is no evidence to support an association between
had a circulating level of 25(OH)D
7   Work hours as a risk factor for SARS-CoV-2 infections

             In addition to the biological factors, which were the subject    REFERENCES
    of this study, it is also necessary to evaluate the occupational          1. Movimento pela Soberania Popular na Mineração (MAM). MPSP na
    factors in which these individuals are inserted. This is because              M. Sudeste do Pará vê crescente de óbitos pela Covid-19 com mineração
                                                                                  a todo vapor [Internet]. Belém: MAM; 2020 Mai; [access in 2020 Jul 14].
    individuals with occupations that require close interpersonal                 Available from: https://mamnacional.org.br/2020/05/27/sudeste-do-para-
    interaction are considered to be at higher risk of acquiring                  ve-crescente-de-obitos-pela-COVID-19-com-mineracao-a-todo-vapor/
                                                                              2. St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G,
    COVID-19. Especially if they are considered essential, such as                Coons M, et al. Sleep duration and quality: impact on lifestyle behaviors
    mining, where there is no possibility of maintaining total social             and cardiometabolic health: a scientific statement from the American
                                                                                  Heart Association. Circulation [Internet]. 2016 Nov; [cited 2020 Jul
    isolation.                                                                    14]; 134(18):367-86. Available from: https://pubmed.ncbi.nlm.nih.
             In the state of Pará, where part of the study was conducted,         gov/27647451/
    data from the health secretariat showed that municipalities, where        3. Peters SAE, MacMahon S, Woodward M. Obesity as a risk factor for
                                                                                  COVID-19 mortality in women and men in the UK biobank: comparisons
    there are large mining projects in this state, are the most affected          with influenza/ pneumonia and coronary heart disease. Diab Obes Metab.
    by COVID-191. At the beginning of the pandemic, until May                     2021 Jan;23(1):258-62. DOI: https://doi.org/10.1111/dom.14199
                                                                              4. Dennis JM, Mateen BA, Sonabend R, Thomas NJ, Patel KA, Hattersley
    20th, 610 contaminations and 49 deaths had been confirmed                     AT, et al. Type 2 diabetes and COVID-19-related mortality in the critical
    (lethality rate of 8.0%); in Canaã dos Carajás, already in Marabá,            care setting: a national cohort study in England, March-July 2020.
    the numbers are even more frightening because of the high                     Diabetes Care. 2021 Jan;44(1):50-7. DOI: https://doi.org/10.2337/
                                                                                  dc20-1444
    percentage of lethality, since 280 contaminations with 53 deaths          5. Asif N, Iqbal R, Nazir CF. Human immune system during sleep. Am J
    have been identified, that is, an astounding lethality rate of 18.9%,         Clin Exp Immunol [Internet]. 2017 Dec; [cited 2020 Jul 7]; 6(6):92-6.
                                                                                  Available from: http://www.ncbi.nlm.nih.gov/pubmed/29348984
    much higher than the national average.                                    6. Précoma DB, Oliveira GMM, Simão AF, Dutra OP, Coelho OR, Izar
             A review study conducted by the European Centre for                  MCO, et al. Updated cardiovascular prevention guideline of the Brazilian
    Disease Prevention (ECDC-19), examining whether outbreaks                     society of cardiology – 2019. Arq Bras Cardiol. 2019 Oct;113(4):787-891.
                                                                              7. Ferreira CES, Maeda SS, Batista MC, Lazaretti-Castro M, Vasconcellos
    in occupational settings in the European economic area and the                LS, Madeira M, et al. Posicionamento oficial da Sociedade Brasileira de
    United Kingdom were associated with occupational clusters,                    Patologia Clínica/Medicina Laboratorial e da Sociedade Brasileira de
                                                                                  Endocrinologia e Metabologia. J Bras Patol Med Lab [Internet]. 2018;
    reported that factors potentially related to a higher risk of                 [cited ANO Mês dia]; 53(6):377-81. Available from: http://bibliotecasbpc.
    infection by SARS-CoV-2 may be the contact of workers in                      org.br/arcs/pdf/PosicionamentoOficial_SBPCML_SBEM_2018.pdf
    closed environments, such as in the use of elevators and shared           8. Oliveira Junior EP, Montenegro Junior RM, Vencio S. Diretrizes da
                                                                                  Sociedade Brasileira de Diabetes 2017-2018. São Paulo: Editora Clannad;
    bathrooms21. Besides, shift workers in the mining industry are                2017.
    frequently submitted to agglomerations in the work routine, such          9. Drager LF, Lorenzi-Filho G, Cintra FD, Pedrosa RP, Bittencourt LRA,
                                                                                  Poyares D, et al. 1o Posicionamento brasileiro sobre o impacto dos
    as in lodgings, shift changes, and in the transportation provided             distúrbios de sono nas doenças cardiovasculares da Sociedade Brasileira
    by the company, which can vary from 5 to 46 passengers in cars                de Cardiologia. Arq Bras Cardiol. 2018;111(2):290-341.
    and buses, respectively, in trips that can last up to 2 hours. In         10. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T,
                                                                                  Davidson KW, et al. Presenting characteristics, comorbidities, and
    addition to the cafeterias, the self-service model presents a great           outcomes among 5700 patients hospitalized with COVID-19 in the
    risk of food contamination with droplets of saliva and the use                New York City area. JAMA [Internet]. 2020 May; [cited 2020 Jul 14];
                                                                                  323(20):2052. Available from: https://jamanetwork.com/journals/jama/
    of common serving utensils and should be abandoned. This can                  fullarticle/2765184
    be a great source of contamination.                                       11. Centro Técnico Científico (CTC). Pontifícia Universidade Católica do Rio
             During a pandemic, managers should provide good                      de Janeiro (PUC-Rio). Diferenças sociais: pretos e pardos morrem mais de
                                                                                  COVID-19 do que brancos, segundo NT11 do NOIS [Internet]. Rio de
    transportation conditions that respect the guidance of social                 Janeiro: CTC/PUC-Rio; 2020; [access in 2020 Jul 14]. Available from: http://
    distancing, in addition to the constant sanitation of places with a           www.ctc.puc-rio.br/diferencas-sociais-confirmam-que-pretos-e-pardos-
                                                                                  morrem-mais-de-COVID-19-do-que-brancos-segundo-nt11-do-nois/
    high turnover of people. In the cafeterias, the self-service model        12. Markwald RR, Melanson EL, Smith MR, Higgins J, Perreault L, Eckel
    should be abandoned due to the high risk of food contamination                RH, et al. Impact of insufficient sleep on total daily energy expenditure,
    with partridges and the use of common serving utensils.                       food intake, and weight gain. Proc Natl Acad Sci U S A [Internet]. 2013
                                                                                  Apr; [cited 2020 Jul 14]; 110(14):5695-700. Available from: https://www.
             In this context, mining shift workers may not initially              ncbi.nlm.nih.gov/pmc/articles/PMC3619301/
    be classified as at risk for severe forms of COVID-19 because             13. Ryan PM, Caplice NM. Is adipose tissue a reservoir for viral spread, immune
                                                                                  activation, and cytokine amplification in coronavirus disease 2019?. Obesity.
    they are young and supposedly healthy individuals. Although                   2020 Jul;28(7):1191-4. DOI: https://doi.org/10.1002/oby.22843
    their exposure to occupational risk factors, to the shift system,         14. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano
    which directly affects sleep and negatively influences immunity,              JL, et al. Evidence that vitamin D supplementation could reduce risk
                                                                                  of influenza and COVID-19 infections and deaths. Nutrients [Internet].
    added to the individual’s health conditions of favorable infection            2020 Apr; [cited 2020 Jul 8]; 12(4):988. Available from: https://www.
    to COVID-19 leads us to believe in their greater susceptibility               mdpi.com/2072-6643/12/4/988
                                                                              15. Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2
    to acquiring the most serious forms of the disease. The specific              positivity rates associated with circulating 25-hydroxyvitamin D levels.
    characteristics of this population call the attention of the scientific       PLoS One. 2020 Sep;15(9):e0239252. DOI: http://dx.doi.org/10.1371/
                                                                                  journal.pone.0239252
    community and must be carefully evaluated in future studies.              16. Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M,
                                                                                  Merle U. Vitamin D deficiency and outcome of COVID-19 patients.
    ACKNOWLEDGEMENTS                                                              Nutrients [Internet]. 2020 Sep; [cited ANO Mês dia]; 12(9):2757.
                                                                                  Available from: https://www.mdpi.com/2072-6643/12/9/2757
           This study was funded by CNPq-Brazil, professor’s                  17. Atmosudigdo IS, Pranata R, Lim MA, Henrina J, Yonas E, Vania R, et al.
    productivity financial support and CAPES-Brazil-finance code                  Dyslipidemia increases the risk of severe COVID-19: a systematic review,
                                                                                  meta-analysis, and meta-regression. J Clin Exp Hepatol. 2021 Feb 08;
    001, for MSc and PhD student scolarship.                                      [Epub ahead of print]. DOI: https://doi.org/10.1016/j.jceh.2021.01.007

    Sleep Sci. 2021; Ahead of Print
Nascimento RA, et al.    8
18. Codo AC, Davanzo GG, Monteiro LB, Souza G, Muraro S, Virgilio-da-             from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-
    Silva JV, et al. Elevated glucose levels favor Sars-Cov-2 infection and       790X2018000200419&tlng=pt
    monocyte response through a HIF-1α/glycolysis-dependent axis. Cell        20. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-
    Metab. 2020 Sep;32(3):437-46.e5. DOI: https://doi.org/10.1016/j.              angiotensin-aldosterone system blockers and the risk of Covid-19. N
    cmet.2020.07.007                                                              Engl J Med [Internet]. 2020 Jun; [cited 2020 Jul 14]; 382(25):2431-40.
19. Malta DC, Gonçalves RPF, Machado IE, Freitas MIF, Azeredo C,                  Available from: http://www.nejm.org/doi/10.1056/NEJMoa2006923
    Szwarcwald CL. Prevalência da hipertensão arterial segundo diferentes     21. European Centre for Disease Prevention and Control (ECDC).
    critérios diagnósticos, Pesquisa Nacional de Saúde. Rev Bras Epidemiol        COVID-19 clusters and outbreaks in occupational settings in the EU/
    [Internet]. 2018; [cited ANO Mês dia]; 21(Suppl 1):e180021. Available         EEA and the UK. Stockholm: ECDC; 2020.

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