Prognostic Values of Elevated Lactate Dehydrogenase and Creatine Phosphokinase for Disease Severity and Mortality in COVID-19 Patients:
A Retrospective Cohort Study
Authors: Ebrahimi Pouyan , Pakdaman Kimia , Amri Parviz , Shirafkan Hoda , Abedi Seyed Hasan 
Published: August 2024

Background:
The recent coronavirus pandemic caused systemic human disease that killed
many people worldwide, and we are still witnessing the resulting conflicts. Lactate dehydrogenase
(LDH) and Creatine phosphokinase (CPK), markers of muscle damage, are potentially associated
with a more severe Coronavirus disease (COVID-19). This study aims to evaluate the association
between elevated LDH and CPK with severity and mortality in COVID-19 patients.

Methods:
A retrospective single-center study that included 282 patients with COVID-19 was conducted
between 2020-2021 (in Four disease waves) in Rouhani Hospital, Babol, Mazandaran (Northern
Iran). Data were extracted from the medical records of all consecutive patients and followed up
until death or till 9 September 2021. Univariate and multivariate Cox regression analyses were performed
to investigate the associated factors with in-hospital mortality and disease severity. Additionally,
logistics regression analyses and Kaplan-Meier curves were used to determine the association
between LDH and CPK levels and the prognosis of COVID-19 patients.

Results:
The mean age of patients was 60.21 years, and the disease was severe in 31.2% of patients.
About 39 (13.8%) patients died during hospitalization and 20 during the follow-up (280.63 ± 192.85
days). Significantly higher in-hospital mortality among older age patients was observed (p = 0.025),
including those admitted in the first COVID wave (p = 0.015), those having longer hospital admission
(p = 0.008), patients with severe disease (p < 0.001), higher LDH (p = 0.004), higher CPK (p = 0.017),
those needing ICU admission (p < 0.001), needing NIV (p = 0.002), and those needing IMV (p <
0.001). In other words, the severity of COVID-19 was significantly associated with older age (p <
0.001), patients with CVDs (p < 0.001), HTN (p = 0.002), DM (p = 0.02), the duration of hospital stays
(p = 0.015), ICU admission (p = 0.009), need for NIV (p = 0.003), IMV (p < 0.001), and mortality in
long-term follow-up (p = 0.006). However, LDH (p = 0.417) and CPK levels (p = 0.091) were not
significantly related to disease severity. LDH levels had a significant effect on hospitalization (p <
0.001, 95%CI= 1.877 to 8.675, HR= 4.036), short-term (p = 0.011, 95%CI= 1.202 to 4.209, HR=
2.249) and long-term (p = 0.002, 95%CI= 1.427 to 4.738, HR= 2.601) mortality, as well as the length
of hospital stay until intensive care unit (ICU) admission (p = 0.017, 95%CI= 1.186 to 5.490, HR=
2.551). Receiver operating characteristic curve analysis demonstrated an optimal cutoff point of LDH in
the first, third, and fourth waves greater than or equal to 759.53 IU/L, 818.52 IU/L, and 840.92 IU/L,
respectively. The test sensitivities were 61.1%,66.7%, and 75%, respectively; specificities were
88.2%,76.6%, and 79.7%, respectively; the AUCs were 0.722, 0.786, and 0.720, respectively, among all
hospitalized patients. Comparing the areas under fitted ROC curves, serum LDH was significantly associated
with mortality (p < 0.05 for the mentioned cut-off points). However, the area under the curve was
not significant at the aforementioned points found for CPK (p > 0.05 for CPK at all waves).

Conclusion:
Higher levels of LDH, unlike CPK, significantly predicted severity during hospitalization
and mortality in different time periods. Also, its sensitivity increased in new waves. When the
COVID-19 patient is hospitalized, these results can help determine the appropriate diagnostic test.