Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures
Bruna Raphaela Oliveira Silva, Wellington Francisco Rodrigues, Daniela Gomes Pires Abadia, Djalma A Alves Da Silva, Leonardo E Andrade E Silva, Chamberttan S Desidério, Thais Soares Farnesi-De-Assunção, Juliana C Costa-Madeira, Rafaela M Barbosa, Anna V Bernardes E Borges, Andrezza C C Hortolani Cunha, Loren Q Pereira, Fernanda R Helmo, Marcela Rezende Lemes, Laís M Barbosa, Rafael O Trevisan, Malu Mateus Santos Obata, Giovanna F Bueno, Fabiano V Mundim, Ana Carolina M Oliveira-Scussel, Ivan B Monteiro, Yulsef M Ferreira, Guilherme H Machado, Kennio Ferreira-Paim, Hélio Moraes-Souza, Marcos Vinicius Da Silva, Virmondes Rodrigues Júnior, Carlo José Freire Oliveira
Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2022.899702
COVID-19, also known as coronavirus disease 2019, is an infectious viral disease caused by SARS-CoV-2, a novel coronavirus. Since its emergence, its epidemiology has been explored; however, for some regions of the world, COVID-19's behavior, incidence, and impact remain unclear. In continental nations like Brazil, this lack of knowledge results in nonuniform control, prevention, and treatment measures, which can be controversial in some locations. This study aimed to describe the epidemiological profile of patients with COVID-19 in the macroregion of Tria ngulo Sul in the state of Minas Gerais (MG), Brazil. Between March 25 and October 21, 2020, data were collected and statistically analyzed from 395 hospitalized patients in the city of Uberaba, MG, suspected to have moderate or severe forms of the disease. Of the 395 suspected cases, 82% were confirmed to be positive for COVID-19. The mean age of positive patients was 58.4 years, and 60.76% were male. Following these patients throughout their hospitalization, a mortality rate of 31.3% was observed. In the population positive for COVID-19, the risk of death increased by 4% for each year of the patient's age. Likewise, the older the patient, the longer their hospitalization and the higher the risk of developing acute respiratory failure. Among the treatments tested in patients, heparin was associated with protection against mortality, and the absence of anticoagulant use was linked to a more than six times greater risk of death. Finally, comorbidities in patients
ETHICS STATEMENT The studies involving human participants were reviewed and approved by Approved by the Research Ethics Committee of the Hospital de Clıńicas, Universidade Federal do Triangulo Mineiro (HC-UFTM) (approval number: 3.957.676). The patients/ participants provided their written informed consent to participate in this study.
AUTHOR CONTRIBUTIONS CO designed the experiments. BO, WR, DA, DS, LA, CD, TF-d-A, JC-M, RB, AB, AH, LP, FH, ML, LB, RT, MO, GB, FM, AO-S, IM, YF, GM, K-FP, HM-S, MS, and VR performed the experiments. CO and WR analyzed the data. BO, WR, DA, DS, LA, CD, TF-d-A, JC-M, RB, AB, AH, LP, FH, ML, LB, RT, MO, GB, FM, AO-S, IM, YF, GM, KF-P, HM-S, MS, VR, and CO wrote the manuscript. All authors contributed to the article and approved the submitted version.
FUNDING This work was supported by the Federal University of Triangulo Mineiro (UFTM), Fundacão de Amparo à Pesquisa do Estado Minas Gerais (FAPEMIG), National Council for Scientific and Technological Development (CNPq), and Coordination for the Improvement of Higher Education Personnel (CAPES; Finance code 001).
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the..
References
Abd-Elsalam, Noor, Badawi, Khalaf, Esmail et al., Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study, J. Med. Virol,
doi:10.1002/jmv.27122Ahn, Shin, Kim, Lee, Kim et al., Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19), J. Microbiol. Biotechnol,
doi:10.4014/jmb.2003.03011Ahrenfeldt, Otavova, Christensen, Lindahl-Jacobsen, Sex and Age Differences in COVID-19 Mortality in Europe, Wien klin Wochenschr,
doi:10.1007/s00508-020-01793-9Albini, Di Guardo, Noonan, Lombardo, The SARS-CoV-2 Receptor, ACE-2, is Expressed on Many Different Cell Types: Implications for ACE-Inhibitor-and Angiotensin II Receptor Blocker-Based Cardiovascular Therapies, Intern. Emerg. Med,
doi:10.1007/s11739-020-02364-6Arango, Bioestatıśtica: Teoŕica E Computacional
Ataguba, Ataguba, Social Determinants of Health: The Role of Effective Communication in the COVID-19 Pandemic in Developing C oun tr i es . G l o b H e a l t h A c, t i o n,
doi:10.1080/16549716.2020.1788263Bastos, Niquini, Lana, Villela, Cruz et al., COVID-19 E Hospitalizacões Por SRAG No Brasil: Uma Comparacão Atéa 12 a Semana Epidemioloǵica, Cad saude publ,
doi:10.1590/0102-311x00070120Becker, Stadler, Recent Progress in Biodiversity Research on the Xylariales and Their Secondary Metabolism, J. Antibiot,
doi:10.1038/s41429-020-00376-0Behera, Patro, Singh, Chandanshive, Sr et al., Role of Ivermectin in the Prevention of SARS-CoV-2 Infection Among Healthcare Workers in India: A Matched Case-Control Study, PloS One,
doi:10.1371/journal.pone.0247163Billett, Reyes-Gil, Szymanski, Ikemura, Stahl et al., Anticoagulation in COVID-19: Effect of Enoxaparin, Heparin, and Apixaban on Mortality, Thromb. Haemost,
doi:10.1055/s-0040-1720978Byambasuren, Cardona, Bell, Clark, Mclaws et al., Estimating the Extent of True Asymptomatic COVID-19 and its Potential for Community Transmission: Systematic Review and Meta-Analysis, JAMMI. Off. J. Assoc. Med. Microbiol. Infect. Dis. Canada,
doi:10.3138/jammi-2020-0030Cascella, Rajnike, Aleem, Dulebohn, Napoli, Features, Evaluation, and Treatment of Coronavirus (COVID-19)
Cavalcante, Cardoso-Dos-Santos, Bremm, Lobo, Macaŕio et al., COVID-19 in Brazil: Evolution of the Epidemic Up Until Epidemiological Week 20 of 2020, Epidemiol. Serv. Saude,
doi:10.5123/s1679-49742020000400010Chen, Klein, Garibaldi, Li, Wu et al., Aging in COVID-19: Vulnerability, Immunity and Intervention, Ageing Res. Rev,
doi:10.1016/j.arr.2020.101205Chen, Kubo, Ivermectin and its Target Molecules: Shared and Unique Modulation Mechanisms of Ion Channels and Receptors by Ivermectin, J. Physiol,
doi:10.1113/JP275236Crump, Ivermectin: Enigmatic Multifaceted 'Wonder' Drug Continues to Surprise and Exceed Expectations, J. Antibiot,
doi:10.1038/ja.2017.11Ejaz, Alsrhani, Zafar, Javed, Junaid et al., COVID-19 and Comorbidities: Deleterious Impact on Infected Patients, J. Infect. Public Health,
doi:10.1016/j.jiph.2020.07.014Emadi, Chua, Talwani, Bentzen, Baddley, Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19: A Structured Summary of a Study Protocol for a Randomised Controlled Trial, Trials,
doi:10.1186/s13063-020-04819-9Ganesh, Rajakumar, Malathi, Manikandan, Nagaraj et al., Epidemiology and Pathobiology of SARS-CoV-2 (COVID-19) in Comparison With SARS, MERS: An Updated Overview of Current Knowledge and Future Perspectives, Clin. Epidemiol. Glob Health,
doi:10.1016/j.cegh.2020.100694Gomez, Du-Fay-De-Lavallaz, Fugar, Sarau, Simmons et al., Sex Differences in COVID-19 Hospitalization and Mortality, J. Womens Health (Larchmt),
doi:10.1089/jwh.2020.8948Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue Distribution of ACE2 Protein, the Functional Receptor for SARS Coronavirus. A First Step Understanding SARS Pathogenesis, J. Pathol,
doi:10.1002/path.1570Iser, Sliva, Raymundo, Poleto, Schuelter-Trevisol et al., Definicão De Caso Suspeito Da COVID-19: Uma Revisão Narrativa Dos Sinais E Sintomas Mais Frequentes Entre Os Casos Confirmados, Epidemiol. Serv. Saúde,
doi:10.5123/S1679-49742020000300018Jogalekar, Veerabathini, Gangadaran, Novel 2019 Coronavirus: Genome Structure, Clinical Trials, and Outstanding Questions, Exp. Biol. Med. (Maywood),
doi:10.1177/1535370220920540Kaur, Shekhar, Sharma, Sarma, Prakash et al., Ivermectin as a Potential Drug for Treatment of COVID-19: An in-Sync Review With Clinical and Computational Attributes, Pharmacol. Rep,
doi:10.1007/s43440-020-00195-yLippi, Plebani, The Critical Role of Laboratory Medicine During Coronavirus Disease 2019 (COVID-19) and Other Viral Outbreaks, Clin. Chem. Lab. Med,
doi:10.1515/cclm-2020-0240Lopes-Pacheco, Silva, Cruz, Battaglini, Robba et al., Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies, Front. Physiol,
doi:10.3389/fphys.2021.593223Loṕez-Medina, Loṕez, Hurtado, Davalos, Ramirez et al., Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2021.3071Mastrangelo, Pezzullo, De Burghgraeve, Kaptein, Pastorino et al., Ivermectin Is a Potent Inhibitor of Flavivirus Replication Specifically Targeting NS3 Helicase Activity: New Prospects for an Old Drug, J. Antimicrob. Chemother,
doi:10.1093/jac/dks147Medeiros, Ferreira, Junior, Anticoagulacão Profilatica Durante a Internacão Hospitalar Na COVID-19: Revisão De Literatura, Hematol. Transfus Cell Ther,
doi:10.1016/j.htct.2020.10.873Mokhtari, Hassani, Ghaffari, Ebrahimi, Yarahmadi et al., COVID-19 and Multiorgan Failure: A Narrative Review on Potential Mechanisms, J. Mol. Histol,
doi:10.1007/s10735-020-09915-3Morris, Athan, Walder, Bortolasci, O'neil et al., Can Endolysosomal Deacidification and Inhibition of Autophagy Prevent Severe COVID-19?, Life Sci,
doi:10.1016/j.lfs.2020.118541Omer, Ashraf, Javeed, Maqbool, Immunostimulatory Effect of Ivermectin on Macrophage Engulfment and Delayed Type Hypersensitivity in Broilers, J. Anim. Plant Sci
Pallant, SPSS Survival Manual: A Step by Step Guide to Data Analysis Using IBM SPSS
Pereira, Leão, Erustes, Morais, Vrechi et al., Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19, Int. J. Mol. Sci,
doi:10.3390/ijms22084067Rahimi Pordanjani, Hasanpour, Askarpour, Bastam, Rafiee et al., Aspects of Epidemiology, Pathology, Virology, Immunology, Transmission, Prevention, Prognosis, Diagnosis, and Treatment of COVID-19 Pandemic: A Narrative Review, Int. J. Prev. Med,
doi:10.4103/ijpvm.IJPVM_469_20Rajter, Sherman, Fatteh, Vogel, Sacks et al., Use of Ivermectin is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study, Chest,
doi:10.1016/j.chest.2020.10.009Rastogi, Sharma, Nagraik, Aygün, Sȩn, The Novel Coronavirus 2019-Ncov: Its Evolution and Transmission Into Humans Causing Global COVID-19 Pandemic, Int. J. Environ. Sci. Technol,
doi:10.1007/s13762-020-02781-2Reis, Silva, Silva, Thabane, Milagres et al., Effect of Early Treatment With Ivermectin Among Patients With Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2115869Sajid, Iqbal, Muhammad, Sandhu, Khan et al., Effect of Ivermectin on the Cellular and Humoral Immune Responses of Rabbits, Life Sci,
doi:10.1016/j.lfs.2007.02.025Salmanton-Garcıá, Sprute, Stemler, Bartoletti, Dupont et al., COVID-19-Associated Pulmonary Aspergillosis, Emerg. Infect. Dis,
doi:10.3201/eid2704.204895Turci, Holliday, Oliveira, A Vigilancia Epidemioloǵica Diante do Sars-CoV-2: Desafios Para O SUS E a Atencão Primaŕia À, Saude. APS,
doi:10.14295/aps.v2i1.70Udensi, Fagbenro-Beyioku, Effect of Ivermectin on Trypanosoma Brucei Brucei in Experimentally Infected Mice, J. Vector Borne Dis
Valiathan, Ashman, Asthana, Effects of Ageing on the Immune System: Infants to Elderly, Scand. J. Immunol,
doi:10.1111/sji.12413Vallejos, Zoni, Bangher, Villamandos, Bobadilla et al., Ivermectin to Prevent Hospitalizations in Patients With COVID-19 (IVERCOR-COVID19): A Structured Summary of a Study Protocol for a Randomized Controlled Trial, Trials,
doi:10.1186/s13063-020-04813-1Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a Specific Inhibitor of Importin a/b-Mediated Nuclear Import Able to Inhibit Replication of HIV-1 and Dengue Virus, Biochem. J,
doi:10.1042/BJ20120150Yan, Ci, Chen, Chen, Li et al., Anti-Inflammatory Effects of Ivermectin in Mouse Model of Allergic Asthma, Inflammation Res,
doi:10.1007/s00011-011-0307-8Zarulli, Barthold, Jones, Oksuzyan, Lindahl-Jacobsen et al., Women Live Longer Than Men Even During Severe Famines and Epidemics, Proc. Natl. Acad. Sci. U.S.A,
doi:10.1073/pnas.1701535115Zhou, Yang, Chi, Dong, Lv et al., Comorbidities and the Risk of Severe or Fatal Outcomes Associated With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.07.029́stica, E Estados C
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'abstract': '<jats:p>COVID-19, also known as coronavirus disease 2019, is an infectious viral disease '
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'author': 'Rastogi',
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'author': 'Reis',
'year': '2022',
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'author': 'Sajid',
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'year': '2021',
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'author': 'Turci',
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'DOI': '10.5327/Z2447-2123202020142ESP1',
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