key: cord-0735711-kxfth616
authors: Benoit, Justin L.; Benoit, Stefanie W.; de Oliveira, Maria H. S.; Lippi, Giuseppe; Henry, Brandon M.
title: Anemia and COVID‐19: A prospective perspective
date: 2020-09-30
journal: J Med Virol
DOI: 10.1002/jmv.26530
sha: 6d7f2963e9c474b06ee4a5aac85efdeada694b25
doc_id: 735711
cord_uid: kxfth616

nan

To the Editor, In a recent report, Tao et al. 1 described that anemia, diagnosed based on hemoglobin measured within the first 24 h after hospital admission, was independently associated with progression to severe coronavirus disease 2019 . In a recent meta-analysis, we reported a weighted mean difference (WMD) of −6.52 (95% CI, −9.2, −3.85) g/L in the hemoglobin of patients progressing to severe COVID-19 compared to those who did not. 2 This finding was confirmed in another recent prospective study, where we observed a significant trend toward lower hemoglobin values with progressively worse COVID-19 severity (p = .017). 3 Though the results of Tao et al. appear in line with such observations, significant differences between populations with respect to COVID-19 laboratory abnormalities have been noted. As such, these findings need to be validated in other heterogenous cohorts. 4 To that end, we evaluated anemia and its association with inflammatory biomarkers and disease outcomes in a prospective cohort of patients with COVID-19. COVID-19 was defined as the need for intensive care unit (ICU) admission, need for mechanical ventilation, or death. Anemia was defined according to WHO criteria: <120 g/L in females and <130 g/L in males. 5 Laboratory values were compared between groups using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables and performed using R (version 4.0.2), with a p < .05 considered statistically significant.

A total of 49 patients with laboratory-confirmed COVID-19

were included in this investigation, 17 (34.7%) of whom were diagnosed as having anemia at ED presentation. The baseline characteristics of patients with and without anemia are shown in Table 1 .

No differences in age, race, or sex were observed. A higher frequency of coronary artery disease (p = .041), heart failure (p = .005), diabetes Table 2) . Moreover, no difference in the frequency of mild, moderate, and severe anemias was found based on COVID-19 severity (p = .773) ( Table 2 ). Further details of the Cincinnati ED Cohort by peak 30-day severity are presented in Table S1 .

In this prospective study, anemia was a common finding, observed in one-third of patients with COVID-19 at ED presentation. Nonetheless, unlike the observations of Tao et al., 1 we did not find anemia to be strongly associated with progression to severe COVID-19 disease. Moreover, we did not find anemia to be associated with significant elevations in inflammatory biomarkers. Given the lack of association with severe disease, we suspect that the anemia observed at this point in the disease course (i.e., at ED presentation) may be more reflective of anemia of chronic disease (ACD) due to the underlying comorbidities rather than a pathophysiologic process of COVID-19. This hypothesis requires further investigation. On the contrary, it is predictable that a decreased hemoglobin value would play a more significant role as a negative prognostic factor during later stages of hospitalization or in concomitance with clinical deterioration.

In a meta-analysis by Taneri et al., 6 hemoglobin levels were found to be significantly lower in patients with severe COVID-19 as opposed to moderate cases (WMD, −4.08 g/L; 95% CI, −5.12 to 3.05 g/L), in agreement with the observations by Henry et al. 2 Taneri et al., 6 however, also reported that lower hemoglobin levels were observed in patients with older age, a higher percentage of subjects with diabetes, hypertension, and overall comorbidities, suggesting that underlying comorbidities and ACD may play a role in this observation. In an interesting study by Bellmann-Weiler et al., 7 24.7% of COVID-19 patients had anemia at admission, similar to the rate observed in our study and that by Tao et al. 1 They further reported that functional iron deficiency, defined as transferrin saturation of less than 20% and serum ferritin greater than 100 µg/L, was observed in 80.0% of patients upon admission.

The authors also observed anemia to be associated with significantly higher odds of in-hospital mortality (odds ratio, 3 Hyperferritinemia has been strongly associated with poor COVID-19 progression and increased mortality, 2,6 thus immune-mediated disruption of iron homeostasis in patients progressing to severe disease appears a strong possibility and thus the use of FID, as well as ferritin/transferrin ratio, as predictors of COVID-19 severity warrants further investigation. 7 However, we suspect that anemia in moderate and severe cases of COVID-19 is not driven by inflammation alone, but a combination of factors including direct cytopathic injury resultant from infection of circulating erythrocytes or their bone marrow precursors, indirect erythrocyte damage due to hemolytic anemia, and/or thrombotic microangiopathy, as evidenced by elevated LDH and low ADAMTS13. 3, 8, 9 Differences between our findings and that of Tao COPD is associated with ACD and is a risk factor for severe COVID-19. 10 Moreover, differences in the sample size, sampling procedure, and study design may also, in part, contribute to the differences observed.

Our prospective cohort included patients who were discharged from the ED without hospital admission, whereas in Tao Severe anemia 0 (0.0%) 1 (6.3%)

Note: Data presented as frequency (%). Mild anemia: 110-119 g/L for females and 110-129 g/L for males. Moderate Anemia: 80-109 g/L. Severe anemia: <80 g/L.

LETTER TO THE EDITOR | 3

Anaemia is associated with severe illness in COVID-19: a retrospective cohort study

Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis

Red blood cell distribution width (RDW) predicts COVID-19 severity: a prospective, observational study from the Cincinnati SARS-CoV-2 emergency department Cohort

Validation of the corona-score for rapid identification of SARS-CoV-2 infections in patients seeking emergency department care in the United States

Health Organization: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity

Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis

Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection

Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis

A relative ADAMTS13 deficiency supports the presence of a secondary microangiopathy in COVID 19

Chronic obstructive pulmonary disease is associated with severe coronavirus disease 2019 (COVID-19)