Implications of Cardiac Markers in Risk-Stratification and Management for COVID-19 Patients

Pengping Li; Wei Wu; Tingting Zhang; Ziyu Wang; Jie Li; Mengyan Zhu; Yuan Liang; Wenhua You; Kening Li; Rong Ding; Bin Huang; Lingxiang Wu; Weiwei Duan; Yi Han; Xuesong Li; Xin Tang; Xin Wang; Han Shen; Qianghu Wang; Hong Yan; Xinyi Xia; Yong Ji; Hongshan Chen


Crit Care. 2021;25(158) 

In This Article


Our study provides detailed information about the association between cardiac markers and clinical outcomes of COVID-19 patients with or without pre-existing CAD. Patients with abnormal serum levels of cardiac markers, namely, BNP, hs-TNI, α-HBDH, CK-MB, and LDH, had a significantly higher mortality rate than patients with normal serum marker levels. In COVID-19 non-survivors with or without pre-existing CAD, the BNP level measured within one week after admission showed a 5.8-fold and 1.4-fold significant increase from the upper reference limit, respectively. Non-survivors with CAD had no hs-TNI detection on admission, this may be the reason hs-TNI in this cohort showed a delayed abnormal course compared to other biomarkers. Our results demonstrated that BNP together with hs-TNI, CK-MB, and LDH within the first week after admission could act as risk factors for in-hospital mortality.

SARS-CoV-2 uses the ACE2 receptor to facilitate viral entry into target cells, causing multiorgan dysfunction.[4] It has been reported that the mechanism of acute myocardial injury caused by SARS-CoV-2 infection might be related to ACE2.[28] The scRNA-seq analysis in the present study showed that ACE2 was mainly expressed in CM, EC, and FB cell types, suggesting that SARS-CoV-2 receptor-related signaling pathways in myocardial injury may be mainly related to these cell populations. Whether someone has CAD or not, once the patient is infected with the virus, the heart may be severely attacked.

Hoffman et al.[29] recently demonstrated that the initial spike in protein priming by TMPRSS2 is essential for the entry and viral spread of SARS-CoV-2 through interaction with the ACE2 receptor.[30] Compared with COVID-19 patients without CAD, patients with pre-existing CAD had a higher percent of elevated BNP, hs-TNI, α- HBDH, CK-MB, and LDH. There is no difference in mortality between COVID-19 patients with CAD and non-CAD when BNP showed abnormal. However, the difference was observed when they represented elevated α- HBDH, CK-MB, and LDH. A significantly higher expression of TMPRSS2 in CAD patients compared with healthy controls suggested that CAD patient may have a higher risk of SARS-CoV-2 infection than health control. It implies that upregulated TMPRSS2 may be the reason that patients with CAD represented a higher percentage of individuals with abnormal levels of cardiac markers after SARS-CoV-2 infection. The serine protease inhibitor camostat mesylate, approved in Japan to treat diseases, has been shown to block TMPRSS2 activity and is thus an interesting candidate to treat COVID-19 patients with pre-existing CAD.[31,32]

Previous studies have investigated the association between myocardial injury markers and prognosis.[33,34] However, evidence on markers that are appropriate for monitoring myocardial injury in COVID-19 patients timely is lacking. Because of limited space in ICUs, the triage rules for access to intensive care are becoming tougher and tougher.

The results in this study showed that BNP together with hs-TNI, α-HBDH, CK-MB, and LDH within the first week after admission could be used as biomarker for prognosis in COVID-19 patients. These cardiac biomarkers were strongly correlated with inflammatory markers, indicating that cardiac biomarkers may track with overall severity of illness and multisystem organ dysfunction. The first week of admission could be a window for observation and early intervention, i.e. that five markers will precede clinical deterioration or escalation of care.

The survival rate of mild/moderate patients is 100% in our cohort which is the same as previous studies, whose data collected from Wuhan Huoshenshan Hospital in Wuhan, China.[35] Huoshenshan Hospital is an emergency specialty field in response to COVID-19 pandemic in China that could make quick and informed decisions for patients. Mild/moderate patients could receive adequate care and timely treatment after admission. Therefore, it is maybe a significant reason for none of the mild/moderate COVID-19 patients progressed to death.

Some limitations exist in the present study. First, there was some indication bias to exclude cases with missing biomarker data from regression analyses, as sicker cases were having more intensive monitoring of these parameters and so they were more likely to be measured, in addition to being more likely to be elevated and data from larger populations and multiple centers are needed to further verify the results. Second, some data regarding heart dysfunction, such as echocardiography, magnetic resonance, and electrocardiography, were incomplete due to the limited conditions in the isolation ward. Third, timing of cardiac markers elevation was not directly correlated with timing of the clinical worsening of the patient, i.e. patients with high BNP's on admission may already have had more severe disease and so it is simply correlative.