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. 2020 Jul 21;12(7):1992.
doi: 10.3390/cancers12071992.

Clinico-Biological Features and Clonal Hematopoiesis in Patients with Severe COVID-19

Nicolas Duployez  1   2 , Jordane Demonchy  1   2   3 , Céline Berthon  1   2 , Julien Goutay  3 , Morgan Caplan  3 , Anne-Sophie Moreau  3 , Anne Bignon  4 , Alice Marceau-Renaut  1   2 , Delphine Garrigue  4   5 , Imelda Raczkiewicz  1   2 , Sandrine Geffroy  2 , Maxime Bucci  2 , Kazali Alidjinou  6 , Julie Demaret  7 , Myriam Labalette  7 , Thierry Brousseau  8 , Annabelle Dupont  9   10 , Antoine Rauch  9   10 , Julien Poissy  3 , Sophie Susen  9   10 , Claude Preudhomme  1   2 , Bruno Quesnel  1   2
Affiliations

Clinico-Biological Features and Clonal Hematopoiesis in Patients with Severe COVID-19

Nicolas Duployez et al. Cancers (Basel). .

Abstract

Advanced age or preexisting comorbidities have been characterized as risk factors for severe coronavirus disease 2019 (COVID-19) cases requiring hospitalization and intensive care. In recent years, clonal hematopoiesis (CH) of indeterminate potential (CHIP) has emerged as a risk factor for chronic inflammatory background and subsequent aging-associated diseases. The purpose of this study was to identify biological factors (particularly leukocyte subtypes and inflammatory markers) associated with a risk of clinical deterioration (i.e., orotracheal intubation (OTI)) and to determine whether CH was likely to influence clinical and biological behavior in patients with severe COVID-19 requiring hospitalization. Here, we describe clinical and biological features, including the screening of CHIP mutants in a well-annotated cohort of 122 hospitalized patients with a laboratory-confirmed diagnosis of COVID-19 (55% requiring OTI). We showed that elevated white blood cell counts, especially neutrophils and high C-reactive protein (CRP) levels at admission, were associated with an increased requirement of OTI. We noticed a high prevalence of CH (25%, 38%, 56%, and 82% of patients aged <60 years, 60-70 years, 70-80 years, and >80 years) compared to a retrospective cohort of patients free of hematological malignancy explored with the same pipelines (10%, 21%, 37%, and 44%). However, the existence of CH did not significantly impact clinical outcome, including OTI or death, and did not correlate with other laboratory findings.

Keywords: CHIP; COVID-19; DNMT3A; SARS-CoV-2; TET2; clonal hematopoiesis; sequencing.

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Conflict of interest statement

The authors have no relevant conflicts of interest to disclose. Members of the LICORNE scientific committee: Pr Dominique DEPLANQUE (Clinical Investigation Center, CHU Lille), Pr Karine FAURE (Department of Infectious Diseases, CHU Lille), Dr Guillaume LEFEVRE (Department of Immunology, CHU Lille), Dr Enagnon Kazali ALIDJINOU (Department of Virology, CHU Lille), Pr Régis BORDET (Department of Medical Pharmacology, CHU Lille), Dr Marie-Charlotte CHOPIN (Department of Infectious Diseases, CHU Lille), Dr Ilka ENGELMANN (Department of Virology, CHU Lille), Dr Delphine GARRIGUE (Department of Emergency, CHU Lille), Pr Anne GOFFARD (Department of Virology, CHU Lille), Pr Eric KIPNIS (Department of Anesthesia and Critical Care, CHU Lille), Pr Myriam LABALETTE (Department of Immunology, CHU Lille), Pr Marc LAMBERT (Department of Internal Medicine, CHU Lille), Pr David LAUNAY (Department of Internal Medicine, CHU Lille), Pr Daniel MATHIEU (Department of Intensive Care, CHU Lille), Pr Claude-Alain MAURAGE (Department of Anatomopathology, CHU Lille), Pr Julien POISSY (Department of Intensive Care, CHU Lille), Pr Boualem SENDID (Department of Parasitology, CHU Lille), Pr Sophie SUSEN (Department of Hematology, CHU Lille).

Figures

Figure 1
Figure 1
Kinetics of laboratory values (mean (95% CI)) during hospitalization in COVID-19 patients according to the requirement (green) or not (blue) of orotracheal intubation (OTI). (A) C-reactive protein; (B) white blood cell count (WBC); (C) neutrophils.
Figure 2
Figure 2
CH in COVID-19 patients requiring hospitalization. (A) Lollipop plots depicting TET2 and DNMT3A mutations in COVID-19 patients. Black, green, pink, and blue dots indicate frameshift/nonsense, missense, in frame, and splicing mutations, respectively. (B) Molecular landscape showing co-mutations in 55 clonal hematopoiesis-positive patients. Red boxes indicate several mutations within the same gene. (C) Violin plot showing the distributions of variant allele frequencies for TET2 and DNMT3A mutations. (D) Frequency of CH among age groups in COVID-19 patients.
Figure 3
Figure 3
Frequency of individuals with (A,D) clonal hematopoiesis, (B,E) TET2 mutations, and (C,F) DNMT3A mutations in COVID-19 positive patients and patients from the retrospective cohort. Subfigures (D–F) show frequency for males only.
See this image and copyright information in PMC

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