Common laboratory values may provide key insights into patients with COVID-19, the illness caused by the SARS-CoV-2 virus, as well as the viral infection itself. Studies reveal telling associations between severe disease and levels of procalcitonin (PCT) and of cardiovascular markers, as well as thrombocytopenia. Analytes such as D-dimer might signify a higher mortality risk factor in hospitalized patients, while others may be useful in explaining epidemiological findings in COVID-19.

Several studies have explored these associations. In one meta-analysis, Italian researchers reported that risk of severe SARS-CoV-2 infection was nearly five times higher in COVID-19 patients with raised PCT levels. PCT synthesis is inhibited by interferon-gamma (INF)-γ, whose concentration increases during viral infections. “This explains why the frequency of raised PCT (>0.5mg/L) levels in COVID-19 patients at admittance in a cohort of 1,099 Chinese patients has been reported as 5.5%,” study co-author Mario Plebani, MD, of the University Hospital of Padova, Italy, told CLN Stat.

That said, patients with raised PCT levels at admission have a significantly higher risk of developing a bacterial infection, since PCT production and release increases abruptly during bacterial infections. The meta-analysis showed a cumulative odds ratio of 4.76 “with no major differences or inconsistencies among the four studies analyzed, for PCT above the normal reference range for predicting severe COVID-19,” Plebani said.

The meta-analysis only covered four studies. Study authors urged for more trials to validate these findings. In the meantime, clinical labs “should be aware that PCT measurement, namely increased levels, would reflect bacterial coinfection in COVID-19 patients developing severe form of disease,” Plebani said.

Another meta-analysis by some of the same authors found an association between low platelet count and increased risk of severe COVID-19 infection and death. Investigators examined nine studies of 1,779 COVID-19 patients—399 with severe disease—and found that sicker patients had lower platelet counts. In a subgroup analysis, patients who died from the disease had even lower platelet counts. Four studies on the rate of thrombocytopenia revealed a threefold enhanced risk of severe COVID-19 in patients with this condition. This suggests “serious organ malfunction or physiologic decompensation, as well as the development of intravascular coagulopathy, often evolving towards disseminated intravascular coagulation,” said co-author Plebani.

Platelet count is a simple, economic, rapid, and accessible laboratory parameter to discriminate between COVID-19 patients with and without severe disease, he added.

Angiotensin-converting enzyme polymorphism (ACE) is a known factor in coronavirus infection. “The angiotensin-converting 1 (ACE1) enzyme is characterized by a genetic deletion/insertion (D/I) polymorphism in intron 16, which is associated with alterations in circulating and tissue concentrations of ACE,” authors of another paper indicated. They theorized that the differences in prevalence of COVID-19 among continental European countries might in part be due to D/I genotype distribution variability.

Comparing D-allele frequency of the ACE1 gene from 25 European countries against COVID-19 prevalence and mortality, the investigators found a correlation between prevalence of COVID-19 and ACE D allele frequency. Overall, relative frequency of the ACE1 D-allele could account for 38% of the variability of disease prevalence, they reported. Based on these findings, they concluded that “ACE1 D/I polymorphism may be regarded as a confounder in the spread of COVID-19 and the outcome of the infection in various European populations.”

A retrospective, multi-center study of 191 confirmed COVID-19 cases in Wuhan, China, reported that three indicators—higher Sequential Organ Failure Assessment (SOFA) score, a D-dimer ≥1 μg/L, and advanced age—signify higher mortality risk. These markers could help identify patients in the early stages of COVID-19 with a poor prognosis, study authors recommended in their findings, published in The Lancet. Sepsis, septic shock, respiratory and heart failure, and acute respiratory distress syndrome (ARDS) were complications often found in patients. Among those patients who died, half experienced secondary infections, and ventilator-associated pneumonia took place in 31% of patients needing invasive mechanical ventilation.

Writing for the American College of Cardiology, James Januzzi, MD, observed that abnormal cardiac troponin values (hs-cTnI) and elevated B-type natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) are often seen in COVID-19 patients.

“In a recent article summarizing clinical course of patients with COVID-19, detectable hs-cTnI was observed in most patients, and hs-cTnI was significantly elevated in more than half of the patients that died,” Januzzi wrote. Natriuretic peptides, in turn, signify myocardial stress and frequently rise in patients with severe respiratory distress.

Despite these findings, Januzzi cautioned against testing patients for hs-cTnI or natriuretic peptides in the absence of solid clinical information.

“Given the frequency and nonspecific nature of abnormal troponin results among patients with COVID-19 infection, clinicians are advised to only measure troponin if the diagnosis of acute myocardial infarction (MI) is being considered on clinical grounds, and an abnormal troponin should not be considered evidence for an acute MI without corroborating evidence,” he indicated, offering similar advice for BNP or NT-proBNP.

Tying this all together, a systematic literature review and meta-analysis offers the big picture and burden of disease on global healthcare. Reviewing more than 600 articles, investigators analyzed a subgroup of these papers, looking at the characteristics of 656 patients in total. Common symptoms included fever (88.7%), cough (57.6%), and dyspnea (45.6%). More than 20% needed intensive care, 32.8% had ARDS, and nearly 14% of hospitalized patients died from the disease. Overall, patients with comorbidities accounted for the highest burden to healthcare facilities. “As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19,” the authors recommended.

Clinical labs seeking more information about COVID-19 diagnostic test findings can access this resource link created by Nadia Ayala-Lopez, PhD, MLS (ASCP), a clinical chemistry fellow at the Johns Hopkins University School of Medicine in Baltimore.