Predictive Markers for Severe COVID-19 Identified

Elevated lactate dehydrogenase may be a predictive marker of acute respiratory distress syndrome and morality in patients with COVID-19.

Elevated lactate dehydrogenase (LDH) may be a predictive marker of acute respiratory distress syndrome (ARDS) and morality in patients with coronavirus disease 2019 (COVID-19), according to a review published in Clinical Infectious Diseases.

In the first 3 months of 2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread from Asia to the rest of the world causing a pandemic of COVID-19. As a result, there have been unprecedented consequences on human health and the global economy. All age groups and patient populations can be infected and affected by COVID-19, though more severe disease seems to be common among the elderly. The clinical spectrum of COVID-19 ranges from asymptomatic or subclinical to a severe course of illness including organ dysfunction, shock, ARDS, acute cardiac injury, and death.

Since the outbreak in China, there has been an exponential growth curve of published COVID-19 academic literature. However, there is a lack of systemic review that consolidate these findings to better understand predictors of severe disease and the effects of different treatments. Therefore, this systemic review, meta-analysis, and meta-regression investigated the predictive value of laboratory investigations for severe disease and adverse outcomes, and evaluated the efficacy of antivirals and corticosteroids for COVID-19.

The Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed databases were searched to identify original research studies that reported clinical features and treatment outcomes of patients with COVID-19. In total. 45 studies and 4203 patients were included. The primary outcome measures were intensive care unit (ICU) admission rate, mortality rate, and rate of ARDS; ICU admission rate was used as a surrogate marker for severe infection. Secondary outcome measures included other morbidities including respiratory failure, septic shock, coagulopathy, acute cardiac injury, acute kidney injury, secondary infection, length of hospital stay, and discharge rate at the point of study completion.

Of the 45 studies included, the pooled rate of ARDS was 18.4%, of ICU admission was 10.9%, and of mortality was 4.3%. ARDS progressed to respiratory failure in 16.2% of patients. The second and third most common complications observed were secondary infections (8.7% of patients), including ventilator-associated or hospital-acquired pneumonia and acute cardiac injury (7.8% of patients).

The meta-regression showed that increased leukocyte count (P<.0001), increased alanine aminotransferase (P =.024), increased aspartate aminotransferase (P =.0040), elevated LDH (P<.0001), and increased procalcitonin (P<.0001) all predicted ICU admission.

Elevated LDH (P<.0001) predicted ARDS; increased leukocyte count (P =.0005) and elevated LDH (P<.0001) predicted mortality.

Lymphopenia was not found to be a significant predictor of ICU admission, ARDS, or mortality. Furthermore, although no significant benefit was observed in mortality and ARDS rate after treatment with lopinavir-ritonavir, a higher rate of ARDS was associated with corticosteroid treatment (P =.0003).

Limitations of the study included that only studies that were in English and no studies from Europe and the United States were included or available for inclusion for analysis at the time of the literature search. In addition, all of the included studies were observational in nature with no clearly defined clinical parameters or follow-up.

Overall, the review authors concluded that, “Early recognition of severe infection may allow early intervention with supportive measures and therapeutics and improve outcomes.”


Zhang JJY, Lee KS, Ang LI, Leo YS, Young BE. Risk factors of severe disease and efficacy of treatment in patients infected with COVID-19: a systematic review, meta-analysis and meta-regression analysis [published online May 14, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa576/58371

This article originally appeared on Infectious Disease Advisor