key: cord-0994502-jdkga9dh
authors: Guéant, Jean‐Louis; Fromonot, Julien; Guéant‐Rodriguez, Rosa‐Maria; Lacolley, Patrick; Guieu, Régis; Regnault, Véronique
title: Blood myeloperoxidase‐DNA, a biomarker of early response to SARS‐CoV‐2 infection?
date: 2020-08-17
journal: Allergy
DOI: 10.1111/all.14533
sha: 63a3ee1119d7332b18985a2da14134daa77c4b05
doc_id: 994502
cord_uid: jdkga9dh

Convergent arguments suggest that innate immunity related to neutrophils, and in particular neutrophil extracellular traps (NETs), could play a key role in response to SARS-CoV-2 infection.

these arguments, no direct evidence of the spread of NETs into circulation has been produced in the early symptomatic phase of COVID-19 and other viral infections.

We assayed myeloperoxidase-DNA (MPO-DNA) and histone-DNA complexes, two serum markers of circulating NETs, and blood cell counts in 60 consecutive ambulatory subjects attending a screening center for COVID-19 RT-PCR examination of nasopharyngeal swab samples. 5 The study was approved by the Institutional Ethical Committee. All subjects were symptomatic with at least two very recent symptoms among fever, dry cough, and dyspnea since <1 week and most had recent contact with infected cases. They were compared to matched asymptomatic controls recruited several months before the epidemy. The sera were used after completion of biochemical testing ordered by the clinician. The remaining samples were stored in the same conditions among groups, at 20°C in the 24 hours following blood withdrawal. Histone-DNA and MPO-DNA complexes were measured in serum by the Cell Death Detection ELISA Kit (Roche Diagnostics, Sigma Aldrich), using a biotinylated antibody against histones H1, H2A, H2B, H3, and H4 or MPO and a soluble peroxidase-labeled anti-DNA monoclonal antibody, respectively, as described previously. 6 Values were reported in 450 nm absorbance units (AU). Blood cell counts were determined in all subjects. Routine biochemical markers, including hemoglobin, bicarbonate, potassium, sodium, chloride, serum total proteins, C-reactive protein, urea nitrogen, creatinine, bilirubin, conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, lactico-dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase, and creatine kinase, were assayed in a Cobas 8000 Analyzer (Roche Diagnostics).

RT-PCR was positive in 34 subjects (56.6%). The mean age LETTER TO THE EDITOR complexes with markers of blood cell counts predicting severity, including neutrophil, lymphocyte, and platelet counts, and neutrophil-to-lymphocyte ratio ( Figure 2 ) and no correlation with RT-PCR. 2 MPO-DNA was negatively correlated with lymphocytes and platelets, while histone-DNA was positively correlated with neutrophils and neutrophil-to-lymphocyte ratio. The subjects with positive vs negative RT-PCR had decreased blood counts of leucocytes, platelets, neutrophils, and lymphocytes and increased sodium and bicarbonate. We reported no difference in other routine biochemical markers between the two symptomatic groups (Table S1 ) and no correlation of these biochemical parameters with blood levels of MPO-DNA and histone-DNA complexes.

The increase of MPO-DNA and histone-DNA complexes in blood shows that the release of NETs is involved in the early host answer to COVID-19. The release could result from neutrophil exposure to virus particles, cytokine production, and/or response to host damage-associated molecular patterns (DAMPs) produced by infected cells, as reported in other pulmonary viral infections. 3, 4 Our data also show that MPO-DNA blood level is a sensitive marker of the early phase of COVID-19. All positive patients had a level dramatically higher than that observed in controls. Our data suggest to further evaluate MPO-DNA as a early marker, which could help to discriminate symptomatic patients with false-negative RT-PCR from those with negative RT-PCR related to another viral lung infection, in addition to computed tomography. 7 We estimated the number of COVID-19 cases with false-negative RT-PCR to 11 among the 60 symptomatic subjects, considering the 70%-80% sensitivity of RT-PCR usually reported at very early infection step. 7 This estimate is exactly the number of symptomatic negative cases who had a MPO-DNA blood level similar to that reported in symptomatic positive cases. This hypothesis is likely since these symptomatic negative cases had recent contact with infected cases.

The other symptomatic patients with negative RT-PCR could have other viral infections that increase MPO-DNA to a lesser extent than COVID-19. [3] [4] [5] 7 This could explain the intermediate increase 

All authors have no conflict of interest to declare. Vandoeuvre les Nancy, France.

Email: jean-louis.gueant@univ-lorraine.fr

https://orcid.org/0000-0002-5067-042X

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