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TROPONIN MYOCARDIAL INJURY MARKER AND OUTCOME IN COVID-19: SCOPING REVIEW

ABSTRACT

Objective:

To analyze scientific evidence on changes in the myocardial injury marker troponin and clinical outcome in patients hospitalized with COVID-19.

Method:

A scoping review was adopted, in the Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online and Virtual Health Library bases, from May to July 2022. Using as descriptors: Troponin; COVID-19; Cardiovascular System.

Results:

23 studies revealed cardiac alterations in hospitalized patients with COVID-19 by examining the cardio specific biomarker troponin, in addition to relating it to high mortality rates. Studies have shown a great relationship between acute myocardial injury, evidenced by elevated troponin, and a worse outcome during hospitalization.

Conclusion:

Cardiovascular changes were mapped in patients hospitalized with COVID -19 who progressed to severe cases of the disease. This study can contribute to care planning through protocols aimed at clinical management, specific for patients with the disease, both in the acute phase and in the post- COVID -19 phase.

DESCRIPTORS:
Troponin; Cardiovascular System; COVID -19; Nursing.

RESUMO:

Objetivo:

Analisar evidências científicas sobre alterações do marcador de lesão miocárdica troponina e o desfecho clínico em pacientes hospitalizados com Covid-19.

Método:

Adotou-se scoping review, nas bases Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online e Biblioteca Virtual em Saúde, de maio a julho de 2022. Utilizando como descritores: troponin; covid-19; cardiovascular system.

Resultados:

23 estudos revelaram alterações cardíacas em pacientes hospitalizados com Covid-19 pelo exame do biomarcador cardioespecífico troponina, além de relacioná-lo a altas taxas de mortalidade. Estudos têm demonstrado grande relação entre lesão miocárdica aguda, evidenciada por elevação da troponina a um pior desfecho durante a hospitalização.

Conclusão:

Mapearam-se as alterações cardiovasculares de pacientes hospitalizados com Covid-19 que evoluíram para quadros graves da doença. Este estudo pode contribuir para o planejamento assistencial através de protocolos voltados para o manejo clínico, específicos para pacientes com a doença, tanto na fase aguda quando na fase pós Covid-19.

DESCRITORES:
Troponina; Sistema Cardiovascular; Covid-19; Enfermagem.

RESUMEN

Objetivo:

Analizar la evidencia científica sobre los cambios en el marcador de lesión miocárdica troponina y el resultado clínico en pacientes hospitalizados con Covid-19.Método: Se adoptó una revisión del alcance, en las bases Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online y Biblioteca Virtual de Salud, de mayo a julio de 2022. Utilizando como descriptores: troponin; covid-19; cardiovascular system.

Resultados:

23 estudios revelaron alteraciones cardiacas en pacientes hospitalizados por COVID-19 mediante el examen del biomarcador cardioespecífico troponina, además de relacionarlo con altas tasas de mortalidad. Los estudios han demostrado una fuerte relación entre la lesión miocárdica aguda, evidenciada por la elevación de la troponina, y un peor pronóstico durante la hospitalización.

Conclusión:

Se mapearon alteraciones cardiovasculares en pacientes hospitalizados con Covid-19 que progresaron a enfermedad grave. Este estudio puede contribuir a la planificación asistencial mediante protocolos dirigidos al manejo clínico, específicos para pacientes con la enfermedad, tanto en la fase aguda como en la fase post-Covid-19.

DESCRIPTORES:
Troponina; Sistema Cardiovascular; COVID-19; Enfermería.

HIGHLIGHTS

  1. Studies demonstrate troponin changes in patients hospitalized with COVID-19.

  2. Elevated troponin has been correlated with increased mortality.

  3. There is a need to reduce complications caused by COVID-19.

HIGHLIGHTS

  1. Studies demonstrate troponin changes in patients hospitalized with COVID-19.

  2. Elevated troponin has been correlated with increased mortality.

  3. There is a need to reduce complications caused by COVID-19.

INTRODUCTION

The first cases of the novel coronavirus emerged in December 2019 in Wuhan, China. Due to the rapid spread of the disease, in March 2020 the World Health Organization declared a pandemic. The virus was classified by the International Committee on Taxonomy of Viruses as SARS-CoV-21. Advanced age group and comorbidities are considered predisposing factors for high lethality rates of COVID -19. Considering this, preventive and informative measures to combat the spread of the disease have been adopted worldwide22 Pereira MD, Pereira MD, Costa CFT, Santos CKA, Dantas EHM. Epidemiological, clinical and therapeutic aspects of COVID-19. J Health Biol Sci. [Internet]. 2020 [cited in 2022 May 20]; 8(1):1-8. Available in: https://doi.org/10.12662/2317-3076jhbs.v8i1.3297.p1-8.2020.
https://doi.org/10.12662/2317-3076jhbs.v...
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The COVID-19 virus, like other respiratory viruses, is transmitted by droplet and aerosol contact. The clinical manifestations caused by SARS-CoV-2 range from asymptomatic and mild, moderate, and severe cases to severe and critical cases, with more severe signs and symptoms requiring special attention as they show worsening clinical evolution and require hospitalizations33 Tuo H, Li W, Tang L, He B, Yao B, Mao P, et al. Cardiac biomarker abnormalities are closely related to prognosis in patients with COVID-19. Int Heart J. [Internet]. 2021 [cited in 2022 May 20]; 62(1):148-52. Available in: https://doi.org/10.1536/ihj.20-180.
https://doi.org/10.1536/ihj.20-180...
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The manifestations are like Severe Acute Respiratory Syndrome (SARS). However, studies have shown changes not only in the respiratory system, but also in organs and systems, such as the cardiovascular system. Patients infected with SARS-CoV-2 may develop cardiac pathologies or potentiate existing ones: myocardial lesions, arrhythmias, vascular inflammation, acute myocardial infarction, pulmonary thromboembolism, among others, have already been associated with clinical manifestations of the disease11 Carrillo-Esper R, Melgar-Bieberach RE, Tapia-Salazar M, Jacinto-Flores SA, Campa-Mendoza AN, Pérez-Calatayud ÁA, et al. Extrapulmonary manifestations of SARS-CoV-2 infection. Cir Cir. [Internet]. 2020 [cited in 2022 May 12]; 88(5):654-63. Available in: https://doi.org/10.24875/CIRU.20000363.
https://doi.org/10.24875/CIRU.20000363...
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The literature suggests that cardiovascular injury secondary to the virus may be linked to angiotensin-converting enzyme 2 (ACE2), which is linked to the immune system and present in high concentration in the lung and heart. The virus connects via the spike protein to the ACE2 receptor and enters the host cell, where ACE2 is deactivated, contributing to lung injury. As ACE2 has high concentrations in the heart, possibly severe lesions can occur in this organ44 Costa IBS da S, Bittar CS, Rizk SI, Araujo Filho AE de, Santos KAQ, Machado TIV, et al. The heart and COVID-19: what the cardiologist needs to know. Review Article. Arch. Bras. Cardiol. [Internet]. 2020 [cited in 2022 May 22]; 114(5):805-16. Available in: https://doi.org/10.36660/abc.20200279.
https://doi.org/10.36660/abc.20200279...
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In addition to the inflammatory response, patients infected with the novel coronavirus show changes in inflammatory markers such as D-dimer, ferritin, interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein, procalcitonin, leukocyte count and the specific cardiac biomarker Troponin44 Costa IBS da S, Bittar CS, Rizk SI, Araujo Filho AE de, Santos KAQ, Machado TIV, et al. The heart and COVID-19: what the cardiologist needs to know. Review Article. Arch. Bras. Cardiol. [Internet]. 2020 [cited in 2022 May 22]; 114(5):805-16. Available in: https://doi.org/10.36660/abc.20200279.
https://doi.org/10.36660/abc.20200279...
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Troponin, a regulator of muscle contraction, is present in striated and cardiac muscles. It is subdivided into subunits C; I and T. Troponin C (TnC) is directly linked to skeletal muscle fibers and is not considered a marker of specific myocardial injury. Troponins I (TnI) and T (TnT), on the other hand, are directly linked to such injury due to their specific functions55 Borges LP, Jesus RCS de, Moura RL. Use of cardiac biomarkers in the detection of acute myocardial infarction. Revista Eletrônica Acervo Saúde. [Internet]. 2019 [cited in 2022 May 22]; 11(13):e940. Available in: https://doi.org/10.25248/reas.e940.2019.
https://doi.org/10.25248/reas.e940.2019...
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Classified as the gold standard for myocardial injury, troponin can also be evidenced in other clinical conditions, such as myocarditis, electrical cardioversion, cardiac trauma, myositis, pulmonary embolism, and renal failure. Its release occurs gradually in the circulation after cardiomyocyte injury, while in transmural necrosis, release occurs between 2-4 hours after injury, reaching its maximum point around 12 hours; remaining elevated for up to 4-7 days for TnI and 10-14 days for TnT55 Borges LP, Jesus RCS de, Moura RL. Use of cardiac biomarkers in the detection of acute myocardial infarction. Revista Eletrônica Acervo Saúde. [Internet]. 2019 [cited in 2022 May 22]; 11(13):e940. Available in: https://doi.org/10.25248/reas.e940.2019.
https://doi.org/10.25248/reas.e940.2019...
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Since the beginning of the pandemic, health professionals and researchers have spared no effort to unravel the changes and clinical manifestations of COVID-19, and studies are needed to know and describe the main changes in the cardiovascular system. Given this context, there was an interest in identifying the knowledge produced on myocardial injury markers, specifically troponin, in patients with COVID-19.

The objective of this research was to analyze the scientific evidence on changes in the myocardial injury marker troponin and clinical outcome in patients hospitalized with COVID-19.

METHOD

This is a scoping review study, carried out according to the recommendations proposed by the Joanna Briggs Institute, characterized by addressing and reporting on the available evidence on a given topic. The study was conducted in nine stages: title, development of the title and question, introduction, inclusion criteria, search strategy, selection of evidence sources, data extraction, evidence analysis and presentation of results.

To construct the research question, the Population, Concept and Context (PCC) strategy was used, namely: Population: patients hospitalized with COVID-19; Concept: alteration in the troponin marker; Context: hospital care. Based on these definitions, the guiding question was established: what scientific evidence relates the involvement of patients by COVID -19 and the change in the myocardial injury marker troponin?

The bibliographic survey was carried out from May to July 2022, the search period was defined between the years 2019 to 2022. The descriptors used were:” Troponin “,” COVID-19” and” Cardiovascular system “, in the databases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMED), Scientific Electronic Library Online (SciELO) and Virtual Health Library (VHL). The Descriptors in Health Sciences (DeCS) were adopted for Latin American databases and Medical Subject Headings (MeSH) for those in English. Boolean operators were used as shown in Chart 1.

Chart 1
Search strategies for databases related to the research. Cuiabá, MT, Brazil, 2022

Studies published in Portuguese, English and Spanish with different methodological designs were included. The selected studies that answered the guiding question of this review were read in full, and the references were analyzed for additional studies for potential insertion.

Regarding the relevance of the studies, they were reviewed by two independent researchers and there was no disagreement between them. The level of evidence of the studies that comprised the sample of the present study was not assessed, due to the type of review.

Studies published in Portuguese, English and Spanish with different methodological designs were included. The results extracted corresponded to the design, country, authors, journals, conduct and conclusion, in addition to answering the guiding question of the research, being presented in a table, and discussed in a narrative way.

The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) was adopted for the selection and inclusion of studies to assist in the decision-making process, according to Figure 1.

The review studies, based on Resolution No. 510 of 2016, do not require approval by the Research Ethics Committee, and the integrity and authorship of the researched documents are guaranteed.

Figure 1
Flowchart of the search process and summarization of the studies found. Cuiabá, MT, Brazil, 2022

RESULTS

A total of 23 studies were included. Regarding the geographical description, the prevalence was in studies conducted in the United States (21.74%). Studies on COVID-19 and troponin elevation demonstrate the importance of the topic, given the severity of the disease and its relationship with changes in this marker. Therefore, the data were extracted and tabulated as shown in Chart 2.

Chart 2
Characterization of the studies included in the scoping review. Cuiabá, MT, Brazil, 2022

The studies show a concordant relationship with each other regarding troponin changes in hospitalized patients with COVID-19. Elevated serum troponin levels were correlated with deterioration in health and increased mortality in patients with and without heart disease. Troponin elevation was associated with death, mechanical ventilation and intensive care66 Alieva AAM, Reznik REV, Teplova TNV, Batov MBMA, Shnahova SLM, Arakelyan ARA, et al. Predictive value of cardiac troponins in COVID-19. Therapy. [Internet]. 2022 [cited in 2022 July 14]; (3):91-100. Available in: https://doi.org/10.18565/THERAPY.2022.3.91-100.
https://doi.org/10.18565/THERAPY.2022.3....
,2424 Shah P, Doshi R, Chenna A, Owens R, Cobb A, Ivey H, et al. Prognostic value of elevated cardiac troponin I in hospitalized Covid-19 patients. Am J Cardiol. [Internet]. 2020 [cited in 2022 May 12]; 15(135):150-53. Available in: https://doi.org/10.1016/j.amjcard.2020.08.041.
https://doi.org/10.1016/j.amjcard.2020.0...
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A wide range of cardiac manifestations are associated with the interaction between COVID-19 and the cardiovascular system. Specific cardiac biomarkers, such as troponin, provide a useful prognostic tool to help identify patients with severe disease early and allow timely treatment escalation1717 Luchian ML, Motoc AI, Lochy S, Magne J, Roosens B, Belsack D, et al. Troponin T in COVID-19 hospitalized patients: kinetics matter. Cardiol J. [Internet]. 2021 [cited in 2022 June 06]; 28(6):807-15. Available in: https://doi.org/10.5603/CJ.a2021.0104.
https://doi.org/10.5603/CJ.a2021.0104...
,2121 Rezabakhsh A, Sadat-Ebrahimi SR, Ala A, Nabavi SM, Banach M, Ghaffari S. A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system. J Cell Mol Med. [Internet]. 2022 [cited in 2022 July 23]; 26(2):274-86. Available in: https://doi.org/10.1111/jcmm.17122.
https://doi.org/10.1111/jcmm.17122...
,2323 Shafi AMA, Shaikh SA, Shirke MM, Iddawela S, Harky A. Cardiac manifestations in COVID-19 patients-A systematic review. J Card Surg. [Internet]. 2020 [cited in 2022 May 23]; 35(8):1988-2008. Available in: https://doi.org/10.1111/jocs.14808.
https://doi.org/10.1111/jocs.14808...

DISCUSSION

Studies have shown a great relationship between acute myocardial injury, evidenced by elevated troponin in patients hospitalized for COVID-19 and a worse outcome during hospitalization. In this case, individuals who presented changes in the marker require intensive care, in the vast majority, which is a predictor of higher lethality in patients infected with COVID-1911 Carrillo-Esper R, Melgar-Bieberach RE, Tapia-Salazar M, Jacinto-Flores SA, Campa-Mendoza AN, Pérez-Calatayud ÁA, et al. Extrapulmonary manifestations of SARS-CoV-2 infection. Cir Cir. [Internet]. 2020 [cited in 2022 May 12]; 88(5):654-63. Available in: https://doi.org/10.24875/CIRU.20000363.
https://doi.org/10.24875/CIRU.20000363...
,88 Azevedo RB, Botelho BG, Hollanda JVG de, Ferreira LVL, Andrade LZJ de, Oei SSML, et al. Practical Approach to acute coronary syndrome in patients with COVID-19. Int J Cardiovasc Sci. [Internet]. 2021 [cited in 2022 June 18]; 34(1):89-98. Available in: https://doi.org/10.36660/ijcs.20200150.
https://doi.org/10.36660/ijcs.20200150...
,1010 Cao J, Zheng Y, Luo Z, Mei Z, Yao Y, Liu Z, et al. Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease. Theranostics. [Internet]. 2020 [cited in 2022 June 06]; 10(21):9663-73. Available in: https://doi.org/10.7150/thno.47980.
https://doi.org/10.7150/thno.47980...
,1212 Chen Q, Xu L, Dai Y, Ling Y, Mao J, Qian J, et al. Cardiovascular manifestations in severe and critical patients with COVID-19. Clin Cardiol. [Internet]. 2020 [cited in 2022 May 06]; 43(7):796-802. Available in: https://doi.org/10.1002/clc.23384.
https://doi.org/10.1002/clc.23384...
,1515 Kavsak PA, Hammarsten O, Worster A, Smith SW, Apple FS. Cardiac troponin testing in patients with COVID-19: a strategy for testing and reporting results. Clin Chem. [Internet]. 2021 [cited in 2022 July 06]; 67(1):107-13. Available in: https://doi.org/10.1093/clinchem/hvaa225.
https://doi.org/10.1093/clinchem/hvaa225...

16 Lala A, Johnson KW, Januzzi JL, Russak AJ, Paranjpe I, Richter F, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection. J Am Coll Cardiol. [Internet]. 2020 [cited in 2022 June 06]; 76(5):533-46. Available in: https://doi.org/10.1016/j.jacc.2020.06.007.
https://doi.org/10.1016/j.jacc.2020.06.0...

17 Luchian ML, Motoc AI, Lochy S, Magne J, Roosens B, Belsack D, et al. Troponin T in COVID-19 hospitalized patients: kinetics matter. Cardiol J. [Internet]. 2021 [cited in 2022 June 06]; 28(6):807-15. Available in: https://doi.org/10.5603/CJ.a2021.0104.
https://doi.org/10.5603/CJ.a2021.0104...
-1818 Majure DT, Gruberg L, Saba SG, Kvasnovsky C, Hirsch JS, Jauhar R. Northwell health COVID-19 research consortium. usefulness of elevated troponin to predict death in patients With COVID-19 and myocardial injury. Am J Cardiol. [Internet]. 2021 [cited in June 06]; 138:100-6. Available in: https://doi.org/10.1016/j.amjcard.2020.09.060.
https://doi.org/10.1016/j.amjcard.2020.0...
,2222 Sahranavard M, Rezayat AA, Bidary MZ, Omranzadeh A, Rohani F, Farahani RH, et al. Cardiac complications in COVID-19: a systematic review and meta-analysis. Arch Iran Med. [Internet]. 2021 [cited in 2022 May 23]; 24(2):152-63. Available in: https://doi.org/10.34172/AIM.2021.24.
https://doi.org/10.34172/AIM.2021.24...
,2424 Shah P, Doshi R, Chenna A, Owens R, Cobb A, Ivey H, et al. Prognostic value of elevated cardiac troponin I in hospitalized Covid-19 patients. Am J Cardiol. [Internet]. 2020 [cited in 2022 May 12]; 15(135):150-53. Available in: https://doi.org/10.1016/j.amjcard.2020.08.041.
https://doi.org/10.1016/j.amjcard.2020.0...
,2626 Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated troponin in patients with Coronavirus disease 2019: possible mechanisms. J Card Fail. [Internet]. 2020 [cited in 2022 June 11]; 26(6):470-75. Available in: https://doi.org/10.1016/j.cardfail.2020.04.009.
https://doi.org/10.1016/j.cardfail.2020....
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A study carried out with 296 patients in intensive care beds with COVID-19, with the objective of evaluating the prevalence of elevated cardiac troponin levels relating the ability of this marker to predict mortality within 60 days, showed a high prevalence of troponin I elevation in these patients, and those who died showed higher elevation values2727 Sprockel J, Murcia A, Rincon J, Berrio K, Bejarano M, Santofimio Z, et al. Troponina de alta sensibilidade no prognóstico de pacientes internados em terapia intensiva por COVID-19: um estudo de coorte longitudinal latino-americano. Rev. bras. ter. intensiva. [Internet]. 2022 [cited in 2023 Jan. 08]; 34(01):124-30. Available in: https://doi.org/10.5935/0103-507X.20220006-pt.
https://doi.org/10.5935/0103-507X.202200...
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Corroborating this finding and the results of this review, a study showed that 20 to 30% of patients hospitalized with COVID-19 had myocardial injury manifested by troponin elevation, also identifying that ventricular arrhythmias were more frequent in patients with elevation of this marker. The authors also observed that cardiac injury was linked to a worse prognosis of COVID-19, greater need for mechanical ventilation and higher mortality rates. In COVID-19 survivors with cardiac injury, the authors suggest that appropriate clinical trials be conducted to correctly identify such problems and plan appropriate care for the long-term sequelae of post-COVID-19 cardiac syndrome2828 Mitrani RD, Dabas N, Goldberger JJ. COVID-19 cardiac injury: Implications for long-term surveillance and outcomes in survivors. Heart Rhythm. [Internet]. 2020 [cited in 2022 Aug. 26]; 17(11):1984-90. Available in: https://doi.org/10.1016/j.hrthm.2020.06.026.
https://doi.org/10.1016/j.hrthm.2020.06....
.

In line with these findings, in another study that sought to identify the relationship between COVID-19 and the damage the disease could cause to the heart muscle, it was observed that the main cardiovascular complications of post-acute Covid-19 syndrome were atrial and ventricular arrhythmias and bradyarrhythmias. It was related that high mortality and morbidity rates were higher for patients with myocardial lesions. It was also found that there is a direct relationship between COVID -19 and cardiac injury. Thus, the authors consider cardiac follow-up relevant for patients surviving COVID -19, especially those known to have elevated cardiac troponin during hospitalization2929 Elseidy SA, Awad AK, Vorla M, Fatima A, Elbadawy MA, Mandal D, et al. Cardiovascular complications in the Post-Acute COVID-19 syndrome (PACS). Int J Cardiol Heart Vasc. [Internet]. 2022 [cited in 2023 Jan 08]; 28(40):101012. Available in: https://doi.org/10.1016/j.ijcha.2022.101012.
https://doi.org/10.1016/j.ijcha.2022.101...
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An observational cohort study conducted at a University Hospital in Frankufrt in April 2020 already sought to assess the presence of myocardial injury in patients recently recovered from Covid-19. These patients underwent cardiac blood markers and Cardiovascular Magnetic Resonance Imaging (CMRI), which indicated that troponin T was detectable in more than 70% of patients. In addition, ejection fraction was decreased and left ventricular enlargement was observed. Regarding CMR (Cardiovascular Magnetic Resonance), 78% of patients recovered from COVID-19 had abnormal findings, such as increased native T1 of the myocardium3030 Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from Coronavirus disease 2019 (COVID-19). JAMA Cardiol. [Internet]; 2020 [cited in 2022 Sept 29]; 5(11):1265-73. Available in: https://doi.org/10.1001/jamacardio.2020.3557.
https://doi.org/10.1001/jamacardio.2020....
.

These studies corroborate the other results already described in this study, and cardiovascular involvement is evident both in the acute phase of COVID-19 and post COVID-19.

Regarding the limitations of the study, it is emphasized that the sources of evidence are still insufficient, as the information is unlimited and may undergo new approaches as new scientific findings emerge. In addition, the results demonstrated in this study still follow a specifically medical approach bias, with little inclusion of other professions, such as nursing, which represents a fundamental and essential part for the management and clinical approach to patient care in hospital units.

FINAL CONSIDERATIONS

The search for evidence related to the objective of this study was achieved, considering the availability of articles in databases, thus enabling greater depth regarding troponin changes and elevations in hospitalized patients with COVID-19.

Most studies have shown a high mortality rate in patients with altered levels of the cardiac marker troponin, related to a greater chance of hospitalization in an intensive care bed, use of mechanical ventilation and death. Thus, monitoring biomarkers since the patient’s admission will allow a specific care plan to be carried out with the objective of a better prognosis, considering the predisposition of patients affected by COVID-19 to evolve to more severe conditions of the disease or death. The need for follow-up care for patients surviving the disease is also highlighted.

The need to reduce the complications caused by COVID-19 is a professional and scientific challenge, regarding nursing, it can be highlighted that the development of studies such as this one contributes to care planning through the creation of care protocols aimed at specific care and clinical management for patients infected with the disease, both in the acute phase and in the post-COVID-19 phase.

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Associate editor: Dra. Luciana Kalinke

Publication Dates

  • Publication in this collection
    10 Nov 2023
  • Date of issue
    2023

History

  • Received
    06 Mar 2023
  • Accepted
    21 June 2023
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