Introduction
Methods
In this article, we perform a retrospective cohort review study on patients admitted to one academic hospital for Covid‐19 illness. We analyzed basic demographic, clinical, and laboratory data to understand the relationship between lymphocytopenia at the time of hospital admission and clinical outcomes.
Results
We discovered that lymphocyte count is lower (P = .01) and lymphocytopenia more frequent by an odds ratio of 3.40 (95% CI: 1.06‐10.96; P = .04) in patients admitted to the Intensive Care Unit (ICU), a marker of disease severity, relative to those who were not. We additionally find that patients with lymphocytopenia were more likely to develop an acute kidney injury (AKI), a marker of organ failure, during admission by an odds ratio of 4.29 (95% CI: 1.35‐13.57; P = .01).
Conclusion
This evidence supports the hypothesis that lymphocytopenia can be an early, useful, and easily obtained, prognostic factor in determining the clinical course and disease severity of a patient admitted to the hospital for Covid‐19.
1 INTRODUCTION
Coronavirus disease 2019 (Covid‐19) is a predominantly respiratory illness caused by the SARS‐CoV‐2 virus. Data regarding prognostic factors are currently scarce given the novelty of the disease. Prognostic information would aid clinicians in managing patients, who are often left without data‐driven guidelines to make important clinical decisions. It is known that lymphocytopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL, occurs in Covid‐19 and may correlate with increased disease severity1–5; indeed, lymphocytopenia is a common systemic manifestation of many viral illnesses6; in particular, other coronaviruses like Severe Acute Respiratory Syndrome coronavirus (SARS‐CoV) and Middle Eastern Respiratory Syndrome coronavirus (MERS‐CoV) have been demonstrated to cause lymphocytopenia.2 However, few studies have examined whether lymphocytopenia found at the time of admission to the hospital is helpful in understanding the disease course. Here, we set out to study a cohort of patients admitted to the hospital diagnosed with Covid‐19 to determine whether lymphocytopenia, found at the time of admission to the hospital, was associated with disease severity and other clinical outcomes.
2 MATERIALS AND METHODS
Data were obtained for patients admitted to one local, academic, community‐based hospital in Houston, TX, USA. IRB approval was granted by the University of Texas Health Science Center at Houston, Houston, TX, USA. Patients were included if they had a positive diagnosis of Covid‐19 based on a polymerase chain reaction‐based assay to detect the SARS‐CoV‐2 virus or had been diagnosed in the community, were over the age of 18, and were admitted and discharged from the hospital between 03/01/2020 and 05/07/2020. Data were collected and extracted from an electronic medical record system and included many variables, such as demographic, clinical outcomes, and laboratory data. We define severe disease as those patients who required admission to the ICU; non‐severe disease is classified as those admitted to the hospital, but did not require ICU admission. Admission to the ICU was determined by clinical factors, namely respiratory failure and hemodynamic instability. Lymphocytopenia was not part of these criteria. Acute Kidney Injury (AKI) is defined as a rise in serum creatinine > 0.3 mg/dL from baseline within 48 hours at any time during admission (if baseline data were unavailable, the lowest value during admission was presumed to be the baseline; if only one value was available, the patient was not presumed to have an AKI).
2.1 Laboratory data
All laboratory data were collected within 24 hours of admission. Laboratory data were analyzed by our hospital’s hematology laboratory. All laboratory samples are typically processed within hour of receipt. Complete blood counts (CBCs) were measured on automated CBC and differential analyzer (X‐N 3000), if the XN3000 could not classify a WBC an attached module (SP10) automatically made the blood smear slides. This blood smear side was manually loaded onto a cell locator imaging (DM96). Technician classified WBC with differential, if technician had difficulty in interpreting results; the pathologist reviewed the slide. Quality control materials were run every 8 hours. Lymphocytopenia is defined as an absolute lymphocyte count (ALC) < 1.0 × 103 cells/µL. Anemia is defined as hemoglobin < 14 gm/dL for men or < 12 gm/dL for women. Thrombocytopenia is defined as platelet count < 150.0 × 103 cells/µL. Leukopenia is defined as leukocyte count < 4.4 × 103 cells/µL. Leukocytosis is defined as a leukocyte count > 11.0 × 103 cells/µL.
2.2 Data analysis
For statistical analyses, the computer program R and accompanying R studio (version 1.2.5033, Orange Blossom) were used to perform analyses.7, 8 R is an open source statistical software program widely used in the academic research community. For continuous variables, a Welch’s two‐sided t test was performed, assuming variances were unequal between samples. To correct for multiple comparisons, a Bonferroni test was performed to adjust P‐values. For categorical data, a Fisher Exact test was used to make comparisons. For all analyses, a P‐value < .05 was used to reject the null hypothesis that either there was no difference between two samples tested or that samples were independent. Odds ratios and confidence intervals were calculated using the package epiR9 in the R‐studio software. Code is available upon request. Figures were prepared using the ggplot210 software in the R software platform.
3 RESULTS
3.1 Basic population demographics
We obtained a cohort of 57 patients who were admitted to and discharged from the hospital between 03/01/2020 and 05/01/2020. The cohort was predominantly male (59%), obese (average BMI of 32.3 ± 1.19 kg/m2) with an average age of 58.2 ± 2.08 years. Our cohort consisted mostly of patients with minority backgrounds (86%). Thirty‐one percent of patients (N = 18) were admitted to the ICU and mortality was 16% (N = 9). Of note, two patients had a diagnosis of Human Immunodeficiency Virus (HIV) infection. The median Charlson comorbidity index was 4 (1.5‐6), indicating an median 10‐year survival rate of 53%.11 In our study, we found that 50% (9/18) of patients admitted to the ICU required intubation and 38% (7/18) required vasopressors (Table 3). Thus, patients admitted to the ICU were classified as having severe disease given the relatively common occurrence of hemodynamic instability and respiratory failure in this population.
3.2 Lymphocytopenia at the time of admission is related to disease severity in Covid‐19
The average ALC count obtained at the time of admission to the hospital in patients requiring ICU admission was lower (0.8 ± 0.11 × 103 cells/µL) relative to those not needing ICU admission (1.4 ± 0.15 × 103 cells/µL; P = .01; Table 1, Figure 1). Additionally, more patients admitted to the ICU had lymphocytopenia (62%) at the time of admission to the hospital compared to those not admitted to the ICU (32%; P = .04; Table 2). Interestingly, the presence of lymphocytopenia conferred an odds ratio of 3.40 (95% CI: 1.06‐10.96) for admission to the ICU.
Non‐ICU | ICU | Significance | |
---|---|---|---|
Sample size, N | 39 | 18 | — |
ALC | 1.4 ± 0.15 | 0.8 ± 0.11 | *P = .01 |
Hemoglobin | 12.9 ± 0.37 | 11.3 ± 0.54 | P = .08 |
Hematocrit | 38.5 ± 1.38 | 35.4 ± 1.30 | P = .55 |
Platelet count | 202.8 ± 11.84 | 274.7 ± 20.22 | *P = .02 |
WBC | 8.8 ± 0.73 | 10.4 ± 1.13 | P = 1.0 |
Note
- Data are expressed as mean ± SEM. Welch’s two‐sample t test with a Bonferroni post hoc correction for multiple comparisons was used to compare groups. An asterisk indicates a statistically significant result.
- Abbreviations: ALC, Absolute Lymphocyte Count; ICU, Intensive Care Unit; WBC, White Blood Cell count.

FIGURE 1
Non‐ICU
No (%) |
ICU
No (%) |
Odds ratio, OR (95% CI) | Significance | |
---|---|---|---|---|
Sample Size | 39 | 18 | — | |
Lymphocytopenia Frequency | 12 (32), N = 38 | 11 (61) | 3.40 (1.06‐10.96) | *P = .04 |
Anemia Frequency | 19 (49) | 14 (78) | 3.68 (1.03‐13.20) | *P = .04 |
Thrombocytopenia Frequency | 6 (15) | 1 (5) | 0.32 (0.04‐2.91) | P = .41 |
Leukopenia Frequency | 5 (13) | 0 | — | — |
Leukocytosis Frequency | 9 (23) | 6 (33) | 1.67 (0.49‐5.71) | P = .5 |
Note
- Raw count data are presented as the count (% of total sample size). Anemia, thrombocytopenia, lymphocytopenia, and leukopenia are defined in the methods. Fisher’s Exact test was performed to compare groups above. Odds ratio is reported as OR (95% CI). Sample sizes are listed as above, unless otherwise stated, with the value N adjacent to the data point. An asterisk indicates a statistically significant result.
- Abbreviation: ICU, Intensive Care Unit.
3.3 Anemia and platelet count at the time of admission are related to disease severity in Covid‐19
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https://bloodtesteasy.com/eval/