The clinical characteristics of myocardial injury in severe and very severe patients with 2019 novel coronavirus disease

Abstract

We read with interest the recent article published by Yang W et al.,1Yang W. Cao Q. Qin L. et al.Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):a multi-center study in Wenzhou city, Zhejiang, China.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (660) Google Scholar which described the clinical characteristics and imaging manifestations of hospitalized patients with confirmed COVID-19 infection in Wenzhou, Zhejiang, China. The 2019 Novel coronavirus disease (COVID-19) has drawn global intensive attention.2Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (32456) Google Scholar, 3Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (14212) Google Scholar, 4Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; Crossref Scopus (16038) Google Scholar Previous studies suggest that severe COVID-19 may present with acute cardiac injury.2Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (32456) Google Scholar, 3Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (14212) Google Scholar, 4Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; Crossref Scopus (16038) Google Scholar However, few have investigated the cardiac lesion markers and their correlation to disease severity. In this letter, we explored the cardiac lesion biomarkers in patients with severe and very severe COVID-19. We enrolled 34 COVID-19 patients admitted to the West District of Union Hospital of Tongji Medical College from February 5th to February 13rd, 2020. COVID-19 was diagnosed upon admission based on the New Coronavirus Pneumonia Prevention and Control Program (4th edition).5National Health Commission of ChinaNew coronavirus pneumonia prevention and control program.4th edn. 2020Google Scholar Severe COVID-19 was defined as having either one of the flowing criteria: (1) Respiratory distress with respiratory rate more than 30 times/min; (2) Oxygen saturation ≤93% in resting state; (3) PaO2/FiO2≤300 mmHg (1 mmHg = 0.133 kPa); and very severe either one of the flowing: (1) Respiratory failure in need of mechanical ventilation; (2) Shock; (3) Other organ dysfunction. Patients with medical history of cardiovascular disease were excluded. The study was approved by the ethics committee of the local hospital. Demographic data and serum samples were collected upon admission. Laboratory confirmation of COVID-19 was done as recommended.5National Health Commission of ChinaNew coronavirus pneumonia prevention and control program.4th edn. 2020Google Scholar Laboratory test and cardiac lesion markers, including cardiac troponin I (cTnI), myoglobin (Myo), Creatine Kinase (CK), Creatine kinase–MB (CKMB), α-hydroxybutyrate dehydrogenase (HBDB), Lactate Dehydrogenase (LDH), and Aspartate Aminotransferase (AST), were tested by the laboratory department. Data were presented as percentages for categorical variables and median±IQR (Inter Quartile Range) for continuous variables. Simple t-test and Mann-Whitney U test was used to compare continuous variables. Fisher's exact test was used to compare categorical variables. We noted significantly increased cTnI, CK, HBDB and LDH levels in very severe group as compare to severe (Table 1). We then applied Fisher's exact test to determine the positive rate of cardiac lesion markers between severe and very severe patients. Increasingly, the percentage of very severe patients with elevated cTnI levels was markedly higher, with 8/8 patients exhibiting increased cTnI in very severe group, and only 1/26 patient in severe group (P value<0.001). In addition, the abnormal percentage of HBDB and LDH showed no significant difference between 2 groups (Table 2).Table 1Baseline information and cardiac biomarkers in severe and very severe patients with COVID-19.Median(IQR)P valueReferenceSevereVery SevereNumber268Sex(Male%)46.15%62.50%nsage63(58–69)67(66–75)nsCRE(μmol/L)64.2(56.5–74.7)82.6(69.6–98.6)ns57.0–111.0AST(U/L)32(25–45)44(34–56)ns8–40ALT(U/L)34(27–67)49(29–75)ns5–40WBC count(*10^9/L)5.93(4.77–7.45)9.32(6.37–10.99)ns3.50–9.50NEU%78.20(71.10–84.70)86.70(63.50–91.15)ns40.00–75.00LYO%14.30(11.90–18.90)7.60(4.55–16.40)ns20.00–50.00CRP(mg/L)18.87(12.26–43.66)73.00(36.57–116.95)<0.050.00–8.00Cardiac BiomarkerscTnI(ng/L)4.8(2.5–8.4)46.8(34.2–299.8)<0.001<26.2Myo(ng/mL)62.8(33.0–87.7)101.75(59.4–212.4)ns<146.9CK(U/L)88(45–125)199(77–285)<0.0524–194CKMB(U/L)10(17–13)13(10–25)ns0–25HBDB(U/L)245(207–275)453(347–547)<0.0172–182AST(U/L)32(25–45)44(34–56)ns8–40LDH(U/L)287(246–331)513(414–641)<0.01109–245Abbreviations: IQR: inter quartile range; CRE: Creatine; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; WBC: White blood count; NEU%: Neutrophil percentage; LYO%: Lymphocyte percentage; CRP: C reactive protein; cTnI: cardiac troponin I; Myo: myoglobin; CK: Creatine Kinase; CKMB: Creatine kinase–MB; HBDB: α-hydroxybutyrate dehydrogenase; AST: Aspartate aminotransferase; LDH: Lactate Dehydrogenase. Open table in a new tab Table 2Comparation of the severe and very severe patients with normal or elevated cardiac biomarkes.GroupNumbercTnI (ng/L)CK (U/L)HBDB (U/L)LDH (U/L)NormalElevatedNormalElevatedNormalElevatedNormalElevatedSevere26251233422620Very Severe808440808P value<0.001<0.05nsnsAbbreviations: cTnI: cardiac troponin I; CK: Creatine Kinase; HBDB: α-hydroxybutyrate dehydrogenase; LDH: Lactate Dehydrogenase. Open table in a new tab Abbreviations: IQR: inter quartile range; CRE: Creatine; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; WBC: White blood count; NEU%: Neutrophil percentage; LYO%: Lymphocyte percentage; CRP: C reactive protein; cTnI: cardiac troponin I; Myo: myoglobin; CK: Creatine Kinase; CKMB: Creatine kinase–MB; HBDB: α-hydroxybutyrate dehydrogenase; AST: Aspartate aminotransferase; LDH: Lactate Dehydrogenase. Abbreviations: cTnI: cardiac troponin I; CK: Creatine Kinase; HBDB: α-hydroxybutyrate dehydrogenase; LDH: Lactate Dehydrogenase. Recently, a number of studies have described the epidemiological and clinical characters of COVID-19.2Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (32456) Google Scholar, 3Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (14212) Google Scholar, 4Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; Crossref Scopus (16038) Google Scholar A study of 41 patients with COVID-19 has suggested that 12% of the mild and severe cases combined showed increased hyper sensitivity troponin I, suggesting acute myocardial injury.2Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; Abstract Full Text Full Text PDF Scopus (32456) Google Scholar It is also reported that severe acute respiratory syndrome coronavirus (SARS-CoV)6Ksiazek T.G. Erdman D. Goldsmith C.S. et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3544) Google Scholar and Middle East respiratory syndrome coronavirus (MERS-CoV)7Cauchemez S. Fraser C. Van Kerkhove M.D. et al.Middle east respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility.Lancet Infect Dis. 2014; 14: 50-56Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar have caused critical cardiac lesions. In the present study, we have focused on cardiac lesion biomarkers in severe and very severe patients with COVID-19. We have proved elevation of cTnI, CK, HBDB, and LDH in critical cases. It is important to notify that, in very severe group, 8/8 patients exhibit cTnI above reference level; while 1/26 in severe group. This suggests that elevated cTnI could be a potential indicator for critically ill patients. It is worth notifying that among the 8 critically ill patients enrolled, the kidney and liver function markers are not as significantly disturbed as the cardiac lesion markers, suggesting that most patients enrolled have not been suffering from multiple organ dysfunction syndrome (MODS). Thus, the consistently high cTnI levels in very severe group point to the importance that the heart injury could be a distinct, or even lethal feature in very severe COVID-19. Protecting from myocardial injury could be of vital importance in clinical treatment for reducing the mortality rate. The study was limited by small sample size. And we haven't analyzed the echocardiography and MRI for the patients enrolled. Further analysis is needed to determine the etiology. We declare no competing interests. BZ, XM and YW collected the clinical and laboratory data. JS processed statistical analysis. JS and BZ drafted the manuscript. XM and YW revised the final manuscript. XM and YW is responsible for all clinical and laboratory data. This study was funded by the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China (No.XJTU1AF-CRF-2018–025).

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