Low lymphocyte count before COVID-19 heightens death risk

Researchers at the University of Rochester Medical Center have conducted a study suggesting that having a low white blood cell count (lymphocytopenia) prior to exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be associated with an increased risk of dying from coronavirus disease 2019 (COVID-19).

Lymphocyte surrounded by red blood cells, 3D illustration. Image Credit: Kateryna Kon / Shutterstock
Lymphocyte surrounded by red blood cells, 3D illustration. Image Credit: Kateryna Kon / Shutterstock

The study of SARS-CoV-2-infected individuals who also had at least one complete blood count available from the ten years preceding any potential exposure to the virus found that pre-2020 lymphocytopenia was associated with an increased risk of COVID-19-related death.

Xueya Cai and colleagues say patients who had pre-existing lymphocytopenia were at a 1.4-fold greater risk of dying from COVID-19 than people who did not have lymphocytopenia prior to 2020.

“These data show that pre-2020 lymphocytopenia is associated with an increased odds ratio of death,” write the researchers.

“Because the absolute lymphocyte count is almost universally available and easily interpreted, this biomarker of the risk of fatality could be widely useful,” they add.

A pre-print version of the paper is available in the server medRxiv*, while the article undergoes peer review.

Research efforts to identify potential prognostic markers in COVID-19

Since the first cases of COVID-19 were first identified in Wuhan, China, late last year, the causative agent SARS-CoV-2 has now infected more than 35.65 million people globally and caused more than one million deaths.

The clinical course of COVID-19 varies significantly between individuals. For instance, while around one-fifth of people in their seventies who become infected with SARS-CoV-2 develop symptoms of COVID-19, a similar proportion in this age group never develop any symptoms.

Such variable health outcomes have inspired great research efforts to identify potential prognostic biomarkers that may pre-exist the development of COVID-19, such as the presence of co-morbidities or predisposing genetic factors.

Lymphocytopenia during COVID-19 disease course

Lymphocytopenia is a common feature among COVID-19 patients and, importantly, a continuing decrease in the absolute lymphocyte count (ALC) is considered a risk factor for respiratory failure and death.

“Given this association between fatality and lymphocytopenia during COVID-19, we hypothesized that lymphocytopenia prior to any possible infection by the virus could be a risk factor for fatality,” said Cai and team.

To test this hypothesis, the researchers identified 1,337 patients (aged a median of 61 years) with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) who also had at least one complete blood count available from the decade before 2020, thereby ensuring these blood counts pre-dated any possible exposure to the virus.

Pre-existing lymphocytopenia was associated with COVID-19 fatality

Bivariate analysis pointed to an association between pre-existing lymphocytopenia (defined as an ALC of   0.9x109 /L) and COVID-19- related death.

Furthermore, logistic regression analysis adjusting for patient age and the number of ALCs obtained indicated that patients who had pre-existing lymphocytopenia were 1.4 times more likely to die from COVID-19 than those who did not.

The team says the mechanisms underlying the association between a low pre-COVID ALC and an increased fatality risk are unclear.

“There is widespread interest in whether baseline immune-status affects fatality and simply the lymphocyte number may be a reflection of the immune status,” write the researchers.

Alternatively, a reduced ALC may reflect the use of therapies for various different disorders that could only be identified by reviewing each medical record individually, they add.

ALC could be a useful biomarker for fatality risk

Cai and colleagues say that ALC could be widely useful as a biomarker of the risk of COVID-19-related fatality.

“Because the ALC is a simple and almost universally available test, the association of pre-COVID lymphocytopenia with fatality may allow individuals and providers to succinctly communicate personal risk, facilities to streamline the triage of resources for isolation, and epidemiologists to improve pandemic-scale modeling,” concludes the team.

*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:
Sally Robertson

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Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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