Clonal hematopoiesis linked to severe COVID-19

The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to ravage worldwide. It has infected over 63.18 million people and claimed more than 1.46 million lives worldwide.

Some people are at a higher risk of developing severe COVID-19, which can be potentially fatal. The elderly, those with underlying health conditions, and those who are immunocompromised are vulnerable to SARS-CoV-2 infection.

Now, an international team of researchers from the USA, South Korea and Canada has found that clonal hematopoiesis is tied to the risk of severe COVID-19.

Clonal hematopoiesis (CH) occurs when a cell called hematopoietic stem cell, which can develop into various blood cell types, begins to make cells with the same genetic mutation. As a result, these blood cells have a different genetic pattern than the rest of the body's blood cells.

Further, CH, an acquired somatic mutation in the hematopoietic stem and progenitor cells, are linked to advanced age, elevated risk of cardiovascular disease and cancer, and reduced overall survival. Patients with CH also suffer from altered inflammatory profiles associated with worse outcomes of certain infections, including COVID-19.

Association between CH and risk of infection in solid tumor patients. A) Volcano plot of the log(Hazard ratio) of infection with CH using multivariable cox proportional hazards regression. B) Association between CH subtype defined by putative driver status and risk of Clostridium Difficle and Streptococcus/Enterococcus infection using cox proportional hazards regression. All models were adjusted for age, gender, race, smoking, diabetes, cardiovascular disease, COPD/asthma, cancer primary site (if history of malignancy), exposure to cytotoxic cancer therapy.
Association between CH and risk of infection in solid tumor patients. A) Volcano plot of the log(Hazard ratio) of infection with CH using multivariable cox proportional hazards regression. B) Association between CH subtype defined by putative driver status and risk of Clostridium Difficle and Streptococcus/Enterococcus infection using cox proportional hazards regression. All models were adjusted for age, gender, race, smoking, diabetes, cardiovascular disease, COPD/asthma, cancer primary site (if history of malignancy), exposure to cytotoxic cancer therapy.

The study

The study, published on the pre-print server medRxiv*, highlights other potential underlying medical conditions that can increase the risk of severe COVID-19.

To arrive at the study findings, the team investigated the link between CH and COVID-19, including the possibility for an association of CH with the heightened risk of severe COVID-19.

The study participants were divided into two groups – patients with solid tumors treated at Memorial Sloan Kettering Cancer Center (MSK) and previously healthy individuals hospitalized due to COVID-19 between January and April 2020 in a South Korea (KoCH cohort).

The patients' blood from the MSK cohort was previously sequenced using the MSK-IMPACT, a validated targeted gene panel that captures all commonly-mutated CH-associated genes. Of these patients, 1,626 underwent SARS-CoV-2 testing between March and July 2020. About 403 of these patients tested positive for COVID-19.

In the KoCH cohort, 112 previously healthy people without cancer who were hospitalized due to COVID-19, were included. The KoCH cohort was sequenced using a custom targeted NGS panel tailored to fit commonly occurring CH genes.

What the study found

The researchers found that severe COVID-19 was the primary outcome for both groups, which is defined as the presence of low blood oxygen levels or hypoxia, requiring supplemental oxygen.

Of the COVID-19 patients, 23 percent and 61 percent had a severe illness in both cohorts, respectively. In a nutshell, CH was seen in 35 percent of COVID-19 positive cases at MSK and 21 percent in the KoCH cohort.

Conversely, CH was noted in 51 percent and 30 percent of patients with severe and non-severe COVID-19, respectively. Further, CH was reported in 25 percent of the patients with severe COVID-19 and in 15.9 percent of patients with mild to moderate COVID-19.

Since CH has been associated with COVID-19, the researchers wanted to explore the relationship between CH and other types of infections. They analyzed billing codes from more than 14,200 solid tumor patients treated at MSK who had blood sequencing by MSK-IMPACT.

The team mapped the International Classification of Diseases ninth and tenth edition (ICD-9 and ICD-10) billing codes to infectious disease categories.

The study findings showed that CH was linked to infections, such as the Clostridium difficile infection and Streptococcus/Enterococcus infection.

With the study findings, the team concluded that CH is tied to increased COVID-19 severity in cancer and non-cancer patients.

"Our data demonstrate a similar association between CH and increased infection severity. This association may be due to residual confounding by variables that are unknown and unaccounted for in our models," the team explained.

The team recommends that future investigations are crucial to clarify the mechanisms that underlie the link between CH And infection risk. This way, scientists can develop interventions to reduce inflammation, clonal expansion, and infectious sequelae in patients.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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