Monocyte distribution width as a pragmatic screen for SARS-CoV-2 or influenza infection

Abstract

Monocyte distribution width (MDW) is a novel marker of monocyte activation, which is known to occur in the immune response to viral pathogens. Our objective was to determine the performance of MDW and other leukocyte parameters as screening tests for SARS-CoV-2 and influenza infection. This was a prospective cohort analysis of adult patients who underwent complete blood count (CBC) and SARS-CoV-2 or influenza testing in an Emergency Department (ED) between January 2020 and July 2021. The primary outcome was SARS-CoV-2 or influenza infection. Secondary outcomes were measures of severity of illness including inpatient hospitalization, critical care admission, hospital lengths of stay and mortality. Descriptive statistics and test performance measures were evaluated for monocyte percentage, MDW, white blood cell (WBC) count, and neutrophil to lymphocyte ratio (NLR). 3,425 ED patient visits were included. SARS-CoV-2 testing was performed during 1,922 visits with a positivity rate of 5.4%; influenza testing was performed during 2,090 with a positivity rate of 2.3%. MDW was elevated in patients with SARS-Cov-2 (median 23.0U; IQR 20.5-25.1) or influenza (median 24.1U; IQR 22.0-26.9) infection, as compared to those without (18.9U; IQR 17.4-20.7 and 19.1U; 17.4-21, respectively, P < 0.001). Monocyte percentage, WBC and NLR values were within normal range in patients testing positive for either virus. MDW identified SARS-CoV-2 and influenza positive patients with an area under the curve (AUC) of 0.83 (95% CI 0.79-0.86) and 0.83 (95% CI 0.77-0.88), respectively. At the accepted cut-off value of 20U for MDW, sensitivities were 83.7% (95% CI 76.5-90.8%) for SARS-CoV-2 and 89.6% (95% CI 80.9-98.2%) for influenza, compared to sensitivities below 45% for monocyte percentage, WBC and NLR. MDW negative predictive values were 98.6% (95% CI 98.0-99.3%) and 99.6% (95% CI 99.3-100.0%) respectively for SARS-CoV-2 and influenza. Monocyte Distribution Width (MDW), available as part of a routine complete blood count (CBC) with differential, may be a useful indicator of SARS-CoV-2 or influenza infection.

Figure 1

Study Flow Diagram. Abbreviations: ED, Emergency Department; MDW, monocyte distribution width; WBC, white blood cell count; NLR, neutrophil to lymphocyte ratio; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Monocyte Distribution Width (MDW), Monocyte Percentage, White Blood Cell count (WBC), and Neutrophil-to-Lymphocyte ratio in SARS-CoV-2 and Influenza Positive and Negative Patients. The red dotted line represents the normal upper limit for each parameter. Median MDW is above the normal cutoff in patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza but below this cutoff in patients who tested negative. Median monocyte percentage, WBC and NLR values were all within the normal range regardless of infection with SARS-CoV-2 or influenza.

Figure 3

Monocyte Distribution Width (MDW), Monocyte Percentage, White Blood Cell count (WBC), and Neutrophil-to-Lymphocyte ratio in SARS-CoV-2 and Influenza Positive and Negative Immunocompromised Patients. A subgroup analysis was performed to evaluate the performance of each study parameter in immunocompromised patients. The red dotted line represents the normal upper limit for each parameter. Median MDW is above the normal cutoff in patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza but at or below this cutoff in patients who tested negative. Median monocyte percentage was above the normal range in immunocompromised patients who tested positive for SARS-CoV-2 but not for patients who tested positive for influenza. Median WBC and NLR values were within the normal range regardless of infection with SARS-CoV-2 or influenza.

Figure 4

Monocyte Distribution Width (MDW) in SARS-CoV-2 Positive and Negative Patients Stratified by Illness Severity. The red dotted line represents the normal upper limit for each parameter. Median monocyte distribution width (MDW) is above the normal cutoff in patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of illness severity but below this cutoff in patients who tested negative with the exception of those who required intensive care unit (ICU) admission. MDW increased with increasing illness severity in SARS-CoV-2 negative patients.

Figure 5

Monocyte Distribution Width (MDW) in Influenza Positive and Negative Patients Stratified by Illness Severity. The red dotted line represents the normal upper limit for each parameter. Median monocyte distribution width (MDW) is above the normal cutoff in patients who tested positive for influenza regardless of illness severity but below this cutoff in patients who tested negative with the exception of those who were hospitalized or required intensive care unit (ICU) admission. MDW increased with increasing illness severity in influenza negative patients.