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A low lymphocyte count in people presenting to the hospital with COVID-19 could help physicians identify those at higher risk for intensive care unit (ICU) admission, new evidence suggests.
Patients with lymphocytopenia had a more than threefold increased risk for requiring ICU care compared with people with normal lymphocyte counts at time of admission. Acute kidney injury (AKI) also was more common among people with low absolute lymphocyte counts.
With COVID-19, the severity of disease can vary widely. "Some patients have minimal to no symptoms, while others develop severe, debilitating disease requiring ICU admission. Prognostic markers are needed to triage these patients," co-author Ahmad Farooq, MD, from the Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Texas Health Science Center at Houston, and from the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Duke University, Durham, North Carolina, told Medscape Medical News.
Farooq, lead author Jason Wagner, MD, from the Department of Internal Medicine, University of Texas Health Science Center, and colleagues reported the results of their retrospective cohort study online July 10 in the International Journal of Laboratory Hematology.
"This study shows that absolute lymphocyte count below 1000 on admission is associated with ICU admission and organ damage, as noted by acute kidney injury," said Farooq.
Prior research has linked lymphocytopenia with other viral illnesses, including severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Although the mechanism driving a reduction of lymphocytes in COVID-19 remains unknown, "this is thought to be due to reduction of peripheral T cells by lymphocyte sequestration in specific target organs," Farooq said. Target organs include the lung, the gastrointestinal tract, and lymphoid tissue.
To find out more, the researchers assessed electronic medical records for 57 adults diagnosed with COVID-19. All participants were admitted to an academic, community-based hospital in Houston between March 1 and May 7, 2020.
A total of 18 people (31%) were admitted to the ICU. Half of this group required intubation, and seven of the patients received vasopressors.
The average age of the study population was 58 years, 59% were men, and the average body mass index was 32 kg/m2. The majority of participants (86%) were of minorities.
A larger proportion of patients who were admitted to the ICU had lymphocytopenia (62%) at the time of hospital admission compared to those who were not admitted to the ICU (32%). Lymphocytopenia at hospital admission translated to an odds ratio of 3.40 (P = .04).
"Our data suggest absolute lymphocyte count can serve as [a] simple test on admission to predict the severity of disease," Farooq said.
The investigators wanted to correlate this finding with clinical outcomes. They found that participants with lymphocytopenia (68%) were more likely to develop AKI during their hospital stay than patients who did not have lymphocytopenia (33%). AKI was defined as an increase in serum creatine of >0.3 mg/dL within 48 hours.
Those with low lymphocyte counts were about four times more likely to develop AKI (odds ratio, 4.29; P = .01).
"It is apparent here that lymphocytopenia may serve as a prognostic marker for AKI in patients with COVID -19," Farooq said.
Nine of the 57 participants died while in the hospital.
Other Possible Implications
People with lymphocytopenia at admission also were more likely to need intubation and vasopressors and to have an ICU stay longer than 7 days. There was also a trend toward higher mortality in the lymphocytopenia group. However, these factors did not differ significantly between groups.
The researchers note that a prior study linked COVID-19 and AKI to higher mortality. "Although lymphocytopenia was not seen to be associated with mortality in this study, the finding of association with AKI warrants further research."
Use of an easily obtained laboratory value and inclusion of a predominantly minority population were strengths of the study, the researchers say. A small sample size and conducting the study in a single community hospital were possible limitations.
"We plan to do a prospective study to further validate these findings," Farooq said. "My lab is also studying gastrointestinal involvement in patients with COVID-19."
Considerable Clinical Utility?
"This is an interesting study," E. John Wherry, PhD, who was not affiliated with the research, told Medscape Medical News when asked to comment.
"There is a lot of emerging evidence about lymphopenia in COVID-19 patients. Sicker patients do appear to have more severe lymphopenia," Wherry said.
"The idea from the paper that lymphopenia may be prognostic and allow the identification of patients on a more severe disease trajectory could have considerable clinical utility," said Wherry, director of the Institute for Immunology and the Wherry Lab at the University of Pennsylvania in Philadelphia.
"It will be interesting in the future to determine the cause of this lymphopenia and interrogate whether lymphopenia contributes to lack of control of infection," he added.
Findings Make Sense
"This is not a surprising finding, as lymphocytes are essential for maintaining an effective and balanced immune response against SARS-CoV-2," Brandon Michael Henry, MD, a CICU research fellow in the Division of Cardiology at Cincinnati Children's Hospital Medical Center, told Medscape Medical News.
Henry added that repletion of lymphocytes during the course of illness may be key to recovery and survival for patients with COVID-19.
"These results are consistent with the literature to date and provide further evidence for the inclusion of lymphocyte count in risk stratification models for COVID-19," said Henry, lead author of a meta-analysis published June 25 that assessed hematologic, biochemical, and immune biomarker abnormalities associated with more severe COVID-19 illness.
The authors, Wherry, and Henry have disclosed no relevant financial relationships.
Int J Lab Hematol. Published online July 10, 2020. Full text
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