Preinfection laboratory parameters may predict COVID-19 severity in tumor patients

Abstract

Background: Infection with SARS-CoV-2 leads to COVID-19, the course of which is highly variable and depends on numerous patient-specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID-19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID-19 in patients with cancer is of great importance.

Methods: Patients diagnosed with solid tumors or hematological malignancies and PCR-confirmed SARS-CoV-2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients' cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS-CoV-2 infection was graded according to the WHO.

Results: A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS-CoV-2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID-19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS-CoV-2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID-19-related death.

Conclusion: The course of COVID-19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID-19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.

Keywords: COVID-19; SARS-CoV-2; biomarkers; cancer; neutrophils; tumor.

FIGURE 1

COVID‐19 disease severity in dependence of the underlying tumor disease. (A) COVID‐19 disease severity of patients with solid or hematological neoplasm was graded as either asymptomatic, mild, moderate, severe, or critical, according to the definitions of the WHO. COVID‐19‐related deaths are also indicated. (B) COVID‐19 disease severity is shown for patients with different tumor entities. Where indicated, patients with different tumor diseases were grouped according to the organ system involved. The heights of the bars correspond to the numbers of patients with the respective tumor entity. The colors within the bars represent the proportion of patients falling into the respective COVID‐19 disease severity category. ICU, intensive care unit; CNS, central nervous system; MPN, myeloproliferative neoplasm; MDS, myelodysplastic syndrome

FIGURE 2

COVID‐19 disease severity in patients treated with various antitumor drugs. Patients treated with targeted, immunomodulatory or antihormonal drugs, as indicated, were grouped on the basis of the substance they received. COVID‐19 disease severity was graded as in Figure 1 and is shown for each subgroup. Each colored dot represents the treatment of a single patient. The three patients treated with cdk4/6 inhibitors also received antihormonal treatments and therefore are represented by dots in both categories

FIGURE 3

COVID‐19 disease severity in dependence of preinfection absolute neutrophil count and CRP. (A) Peripheral blood samples, that had been obtained at least 10 days (median 21 days) prior to the diagnosis of SARS‐CoV‐2 infection as part of clinical routine, were considered as preinfection samples and used for analysis. Each dot represents the time point of the blood sample of an individual patient with respect to his SARS‐CoV‐2 diagnosis. For each laboratory parameter, patients were divided into two groups using the median of all patients as a threshold. (B) COVID‐19 disease severity for patients with neutrophils (left) or CRP (right) below or above the median of all patients. The heights of the bars correspond to the numbers of patients of the respective group. The colors within the bars represent the proportion of patients falling into the respective COVID‐19 disease severity category. (C) COVID‐19‐related mortality for patients with neutrophils below or above the median of all patients. Shown is the mortality rate of the total cohort (left) or the subgroups indicated (right). *, p < 0.05. (D) Preinfection neutrophil counts and CRP values were compared in groups of patients surviving or not surviving COVID‐19. Shown are beeswarm box plots, with each dot representing one patient. *, p < 0.05. (E) Preinfection neutrophil counts and CRP values were used to calculate a score of 0, 1, or 2 points. Shown is the COVID‐19‐related mortality of patients grouped according to this score. p‐values < 0.05 were considered to be statistically significant. CRP, C‐reactive protein