Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

Cardiac damage in patients with the severe type of coronavirus disease 2019 (COVID-19)

BMC Cardiovascular Disorders volume 20, Article number: 479 (2020) Cite this article

Abstract

Background

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Studies showed COVID-19 affected not only the lung but also other organs. In this study, we aimed to explore the cardiac damage in patients with COVID-19.

Methods

We collected data of 100 patients diagnosed as severe type of COVID-19 from February 8 to April 10, 2020, including demographics, illness history, physical examination, laboratory test, and treatment. In-hospital mortality were observed. Cardiac damage was defined as plasma hypersensitive troponin I (hsTnI) over 34.2 pg/ml and/or N-terminal-pro brain natriuretic peptide (NTproBNP) above 450 pg/ml at the age < 50, above 900 pg/ml at the age < 75, or above 1800 pg/ml at the age ≥ 75.

Results

The median age of the patients was 62.0 years old. 69 (69.0%) had comorbidities, mainly presenting hypertension, diabetes, and cardiovascular disease. Fever (69 [69.0%]), cough (63 [63.0%]), chest distress (13 [13.0%]), and fatigue (12 [12.0%]) were the common initial symptoms. Cardiac damage occurred in 25 patients. In the subgroups, hsTnI was significantly higher in elder patients (≥ 60 years) than in the young (median [IQR], 5.2 [2.2–12.8] vs. 1.9 [1.9–6.2], p = 0.018) and was higher in men than in women (4.2 [1.9–12.8] vs. 2.9 [1.9–7.4], p = 0.018). The prevalence of increased NTproBNP was significantly higher in men than in women (32.1% vs. 9.1%, p = 0.006), but was similar between the elder and young patients (20.0% vs. 25.0%, p = 0.554). After multivariable analysis, male and hypertension were the risk factors of cardiac damage. The mortality was 4.0%.

Conclusions

Cardiac damage exists in patients with the severe type of COVID-19, especially in male patients with hypertension. Clinicians should pay more attention to cardiac damage.

Peer Review reports

Introduction

Since the novel coronavirus–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses [1], was discovered in December 2019, it quickly spread throughout China and other countries [2,3,4,5]. As of April 30, 2020, SARS-CoV-2 has broken out in 213 countries, areas and territories with 3,090,445 confirmed cases and 217,769 deaths [6]. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 could be classified into four clinical types: mild, moderate, severe and critical types [7]. More than 80% are mild or moderate with relatively good short-term prognosis due to the self-limiting process according to the study with 44,672 confirmed COVID-19 cases released by the Chinese Center for Disease Control and Prevention on February 17, 2020 [8]. However, 6,168 (13.8%) cases belonged to the severe type and were more likely to develop into the critical type followed by a death rate of 49%, far beyond the average mortality of 2.3%.

Researchers have reported that patients with COVID-19 had acute cardiac injury, which is associated with a higher risk of in-hospital mortality [4, 9, 10]. However, studies focusing on cardiac damage in patients with the severe COVID-19 are few.

In this study, we aim to investigate the clinical findings and cardiac damage in patients with the severe type of COVID-19, and hope to contribute to the prevention and treatment.

Methods

Study population

We retrospectively collected data of all 100 patients at the Sino-French New Town area of Tongji Hospital, Wuhan, where was aided and charged by the medical team of Beijing Hospital from February 8 to April 10, 2020. Patients were all diagnosed as COVID-19 and classified into the severe type according to the Diagnosis and Treatment of Pneumonia Infected by Novel Coronavirus (5th trial edition) pressed by the General Office of the National Health Commission and the General Office of the National Administration of Traditional Chinese Medicine [7]. Severe type met at least one of the following criteria: (1) dyspnea, respiratory frequency ≥ 30/minute, (2) blood oxygen saturation ≤ 93% at rest, (3) PaO2/FiO2 ratio ≤ 300. Critical type met at least one of the following criteria: (1) respiratory failure with mechanical ventilation, (2) septic shock, (3) transferred to the intensive care unit due to multiple organ failure. Patients with acute coronary syndrome or acute heart failure at admission or in the latest one month were excluded. This study was approved by the Ethics Commission of Beijing Hospital (2020BJYYEC-035–01).

Laboratory confirmation of SARS­CoV-2 was done by real-time RT-PCR. The protocol was the same as the document published recently [4]. We also examined other respiratory viruses with real-time RT-­PCR, including influenza A virus (H1N1, H3N2, H7N9), influenza B virus, respiratory syncytial virus, parainfluenza virus, adenovirus, SARS coronavirus (SARS-­CoV), and MERS coronavirus (MERS­-CoV). Sputum or endotracheal aspirates were obtained at admission for the identification of possible causative bacteria or fungi.

Data collection

We obtained demographic, illness history, physical examination, laboratory test, management, and outcome data from patients’ medical records. Blood oxygen saturation was measured after oxygen therapy. In-hospital mortality were observed.

Laboratory tests were conducted within 24 h after admission, including a complete blood count, procalcitonin, interleukin-6, ferritin, coagulation profile, renal and liver function, hypersensitive troponin I (hsTnI), and N-terminal-pro brain natriuretic peptide (NTproBNP).

Definition of cardiac damage

Cardiac damage was defined as plasma hsTnI over 34.2 pg/ml and/or NTproBNP above 450 pg/ml at the age age < 50, above 900 pg/ml at the age < 75, or above 1800 pg/ml at the age ≥ 75 [11].

Statistical analysis

Continuous variables were expressed as mean ± SD when they were normally distributed or median (IQR) when they were not, and compared with the t-test or Mann–Whitney U test, respectively; categorical variables were expressed as number (%) and compared by χ2 test or Fisher’s exact test. Logistic regression analysis was performed to identify variables with a significant independent association with cardiac damage. Demographics (age and sex), potential confounders (hypertension, diabetes, cardiovascular disease, and hyperlipidemia), and variables with p ≤ 0.05 in the univariate analysis were adjusted. A two-sided α of less than 0.05 was considered statistically significant. Statistical analyses were done using the SPSS software (version 23) for all analyses.

Results

From February 8 to April 10, 2020, 100 laboratory-confirmed COVID-19 patients were classified as the severe type at the Sino-French New Town area, with an median age of 62.0 years old. 56 (56.0%) cases were men. 69.0% of the patients had comorbidities, of which hypertension, diabetes, and cardiovascular disease were the top three diseases. The initial symptoms were mainly fever, cough, chest distress, and fatigue. Ten patients had oxygen saturation below 93% after nasal oxygen supply at admission (Table 1).

Table 1 Demographics and clinical characteristics of severe COVID-19
Full size table

Cardiac damage occurred in 25 patients. (Table 2) Increased hsTnI was in 9 (9.0%) patients; increased NTproBNP was in 22 (22.0%) patients. Subgroup analysis showed that significant age and sex differences in hsTnI. (Tables 3, 4) The elderly patients had higher plasma hsTnI levels, so did the males, who also had significantly higher NTproBNP levels than the females. Although NTproBNP level was far higher in the elder, the statistical difference disappeared when taking the effect of age on NTproBNP into consideration.

Table 2 Laboratory characteristics of severe COVID-19
Full size table
Table 3 Age differences in cardiac damage in patients with severe type of COVID-19
Full size table
Table 4 Sex differences in cardiac damage in patients with severe type of COVID-19
Full size table

Patients with cardiac damage had a higher proportion of hypertension and diabetes, compared to those without cardiac damage. White blood count, prothrombin time, d-dimer, creatinine, interleukin-6, procalcitonin, and hsCRP levels were significantly different between the two groups. After adjusting for age, sex, hypertension, diabetes, cardiovascular disease, hyperlipidemia, and variables with significant differences, we found male and hypertension were the risk factors of cardiac damage in patients with severe COVID-19. (Tables 5, 6).

Table 5 Demographics and clinical characteristics of patients with and without cardiac damage
Full size table
Table 6 Logistic multivariable models for determinants of cardiac damage
Full size table

By the end of April 10, 2020, four (4.0%) patients died. In the same period, 96 patients, of which 2 cases deteriorated to critical type but ultimately recovered and discharged from the hospital according to the Criteria of Diagnosis and Treatment of Pneumonia Infected by Novel Coronavirus (5th trial edition). (Table 7).

Table 7 Treatment and outcomes for severe COVID-19
Full size table

Discussion

In this retrospective study, we analyzed data from 100 patients with severe type of laboratory-confirmed COVID-19. Fever, cough, chest distress, and fatigue were common symptoms. Patients with severe COVID-19 also presented lymphopenia, elevated interleukin-6, procalcitonin, and D-dimer. These were consistent with recent researches [3, 4, 12, 13]. More than half of the patients had comorbidities, mainly including hypertension, diabetes, and cardiovascular disease. The prevalence of cardiac damage was 25%. The mortality of severe COVID-19 was 4%.

Huang et al. reported acute cardiac and kidney injuries in COVID-19 patients. In our study, one-quarter of the patients had cardiac damage, suggesting COVID-19 was a systemic disease and SARS-CoV-2 could cause multiorgan damage. The mechanism of cardiac damage resulted from SARS-CoV-2 is unclear. We consider two possible explanations: (1) immune response elicited by the coronavirus may lead to systemic inflammatory response [14, 15]; (2) the virus exists in multiple organ systems to attack tissues [16].

The prevalence of elevated NTproBNP was 22.0% in our study, which was rarely reported previously. Published studies showed that the incidence of myocardial injury presenting elevated hsTnI was 7.2–19.7% in general COVID-19 patients and 23% in critical ill patients, higher than 9.0% in our study [9, 10, 17]. It possibly owes to different criteria of elevated hsTnI, sample sizes, and the phases of COVID-19 breakout.

In subgroups, there was no significant age or sex difference in cardiac damage, but a higher proportion of comorbidities, especially hypertension and diabetes, existed in patients with cardiac damage. After multivariable analysis, we found males and hypertension were the risk factors of cardiac damage. It is consistent with Shi’s report [10]. As all the patients in our study didn’t have an acute coronary syndrome or acute heart failure at admission or in the latest one month, it may suggest that male patients with hypertension are more susceptible to cardiac damage. The possible mechanism is that hypertension-induced cardiac damage is associated with mitochondrial injury, which can be caused by SARS-COV-2 [18, 19]. Estrogen may also play an important protective role in the process [20]. Researchers found cardiac troponins elevation was associated with the male [21, 22].

As of April 10, 96% of the patients were discharged from the hospital. The mortality was 4%, less than the average mortality of severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), which were 11% and 35% [23, 24]. It indicates the prognosis of COVID-19 is generally good. There was no difference in mortality between patients with cardiac damage and those without (0 vs. 5.3%, p = 0.556).

Limitations

Our study has several limitations. First, it’s a study with a small sample size, confounding factors and selection bias are inevitable. Second, we had no data on medication history, electrocardiography, and echocardiography and we can’t describe and discuss the results adequately. Third, we didn’t include the outcomes after patients were discharged from the hospital.

Conclusion

COVID-19 is a systemic disease. Cardiac damage exists in patients with the severe type of COVID-19, especially in male patients with hypertension. Clinicians should pay more attention to cardiac damage. Further studies with large sample size are needed to verify our findings.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

COVID-19:

Coronavirus disease 2019;

SARS­-CoV:

SARS coronavirus

MERS-­CoV:

MERS coronavirus

hsTnI:

Hypersensitive troponin I

NTproBNP:

N-terminal-pro brain natriuretic peptide

References

  1. 1ICTV. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5:536–44.

  2. Chan JF, Yuan S, Kok K, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395:514–23.

    Article  CAS  Google Scholar 

  3. Xu X, Wu X, Jiang X, Xu K, Ying L, Ma C, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606.

    Article  Google Scholar 

  4. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395:497–506.

    Article  CAS  Google Scholar 

  5. Sun K, Chen J, Viboud C. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. Lancet Dig Health. 2020;2:e201–8.

    Article  Google Scholar 

  6. 6WHO COVID-19 Dashboard.2020. https://covid19.who.int/ Accessed 1 May, 2020

  7. 7China NHCO. The Diagnosis and Treatment of Pneumonia Infected by Novel Coronavirus (5th trial edition). 5 February, 2020. https://39.137.20.198/cache/www.nhc.gov.cn/xcs/zhengcwj/202002/3b09b894ac9b4204a79db5b8912d4440/files/7260301a393845fc87fcf6dd52965ecb.pdf?ich_args2=46-24145100054382_b8ed1a1a481d778c43503cdcde88e45c_10001002_9c896c2ed2c1f6d1913c518939a83798_10cabae9adc42948a617b3b1c71d6fff. Accessed 24 February, 2020

  8. Team TNCP. The epidemiological characteristics of an outbreak of 2019 novel coronavirus disease (COVID-19) in China. Chin J Epidemiol. 2020;41:145–51.

    Google Scholar 

  9. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan China. JAMA. 2020;323:1061–9.

    Article  CAS  Google Scholar 

  10. 10Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients WithCOVID-19 in Wuhan, China. JAMA Cardiol. 2020;e200950.

  11. Chinese Medical Association. Chinese Medical Journals Publishing House, Chinese Society of General Practice, Editorial Board of Chinese Journal of General Practitioners of Chinese Medical Association, Expert Group of Guidelines for Primary Care of Cardiovascular Disease. Guideline for primary care of acute heart failure. Chin J Gen Pract. 2019;18:925–30.

    Google Scholar 

  12. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13.

    Article  CAS  Google Scholar 

  13. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–20.

    Article  CAS  Google Scholar 

  14. Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin. 2020;35:266–71.

    Article  CAS  Google Scholar 

  15. Rokni M, Ghasemi V, Tavakoli Z. Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: comparison with SARS and MERS. Rev Med Virol. 2020;30:e2107.

    Article  CAS  Google Scholar 

  16. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323:1843–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respirat Med. 2020;8:475–81.

    Article  CAS  Google Scholar 

  18. Eirin A, Lerman A, Lerman LO. Mitochondrial injury and dysfunction in hypertension-induced cardiac damage. EUR HEART J. 2014;35:3258–66.

    Article  CAS  Google Scholar 

  19. Saleh J, Peyssonnaux C, Singh KK, Edeas M. Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. MITOCHONDRION. 2020;54:1–07.

    Article  CAS  Google Scholar 

  20. Patrizio M, Marano G. Gender differences in cardiac hypertrophic remodeling. Ann Ist Super Sanita. 2016;52:223–9.

    PubMed  CAS  Google Scholar 

  21. Suthahar N, Meems LMG, Ho JE, de Boer RA. Sex-related differences in contemporary biomarkers for heart failure: a review. Eur J Heart Fail. 2020;22:775–88.

    Article  Google Scholar 

  22. Wallace TW, Abdullah SM, Drazner MH, Das SR, Khera A, McGuire DK, et al. Prevalence and determinants of troponin T elevation in the general population. Circulation. 2006;113:1958–65.

    Article  CAS  Google Scholar 

  23. Chan KS, Zheng JP, Mok YW, Li YM, Liu YN, Chu CM, Ip MS. SARS: prognosis, outcome and sequelae. Respirology. 2003;8(Suppl):S36-40.

    Article  Google Scholar 

  24. Badawi A, Ryoo SG. Prevalence of comorbidities in the middle east respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int J Infect Dis. 2016;49:129–33.

    Article  Google Scholar 

Download references

Acknowledgments

None.

Funding

The study was funded by the Beijing Municipal Natural Science Foundation (No. 7192078).

Author information

Author notes

  1. Jing Li and Yinghua Zhang contributed equally to this work

Authors and Affiliations

  1. Division of Cardiology, Beijing Hospital, #1 Dahua Road, Dongcheng District, Beijing, 100730, China

    Jing Li, Fang Wang, Bing Liu, Hui Li, Guodong Tang & You Lv

  2. Division of Cardiology, Xuanwu Hospital Capital Medical University, #45 Changchun Street, Xicheng District, Beijing, 100053, China

    Yinghua Zhang, Jing Gao & Jing Li

  3. Division of Intensive Care Unit, Beijing Hospital, Beijing, 100730, China

    Zhigang Chang

  4. Division of Rheumatology and Immunology, Beijing Hospital, Beijing, 100730, China

    Aihua Liu

  5. Division of Emergency, Beijing Hospital, Beijing, 100730, China

    Chunyi Fu

  6. National Center Research Center of Geriatric Diseases [Xuanwu Hospital], Beijing, 100053, China

    Jing Li

Authors
  1. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yinghua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guodong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhigang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aihua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chunyi Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. You Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jing Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to this work. LJ, GJ and LJ conceived and designed the study; LJ, ZYH, GJ and LJ analyzed the data and drafted the manuscript. All authors revised and approved the final manuscript.

Corresponding authors

Correspondence to Jing Li, Jing Gao or Jing Li.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Commission of Beijing Hospital (2020BJYYEC-035–01). Individual informed consent was waived by the ethics committee listed above because this study used currently existing sample collected during the course of routine medical care and did not pose any additional risks to the patients.

Consent for publication

Not applicable.

Competing interests

All authors have nothing to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Zhang, Y., Wang, F. et al. Cardiac damage in patients with the severe type of coronavirus disease 2019 (COVID-19). BMC Cardiovasc Disord 20, 479 (2020). https://doi.org/10.1186/s12872-020-01758-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12872-020-01758-w

Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

Contact us