Research findings published in the Journal of Medical Virology point to anaemia being an independent risk factor tied to severe coronavirus disease 2019 (COVID‐19), with Zheying Tao, Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues, calling for healthcare professionals to “be more sensitive to the haemoglobin level of COVID‐19 patients” when they are admitted to hospital.
The odds ratio (OR) of anaemia related to severe manifestations of COVID‐19 in the study was 3.47(95% CI: 1.02‐11.75, P=0.046) and 3.77 (95% CI: 1.33‐10.71, P=0.013) after adjusting for baseline data and laboratory indices, respectively.
The retrospective, observational study involved a total of 222 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) admitted to Wuhan Ninth Hospital from December 1, 2019, to March 20, 2020. Among these, 202 were non-severe COVID-19 cases and 20 had severe disease. In addition, 79 (35.6%) of the 222 patients had anaemia, defined as haemoglobin level <120 g/L in women and <130 g/L in men, while the other 143 patients did not.
The authors reported that in severe COVID-19 patients, haemoglobin levels showed a significant decline when compared to non-severe patients (128 g/L vs 111.5 g/L, P=0.002). Further, significantly more patients in the severe group met the diagnostic criteria for anaemia (32.2% vs 70.0%, P=0.001).
The prevalence of severe illness in the anaemic group was significantly higher than that in the non-anaemic group (8.1% vs 17.7%, P=0.001). Compared to patients without anaemia, those with anaemia were older and more likely to have chronic kidney disease (0.0% vs 3.8%), cardiovascular disease (CVD) (3.5% vs 15.2%), and chronic obstructive pulmonary disease (COPD) (0.0% vs 10.1%) (all P<0.05).
COVID-19 patients with anaemia were predisposed to more severe inflammatory responses, coagulation disorders, and organ injuries. Specifically, more patients had elevated levels of C-reactive protein (CRP) (8.5% vs 24.7%) and procalcitonin (PCT) (1.3% vs 15.6%) in the anaemic group (all P<0.05). Patients with anaemia also showed significantly higher levels of erythrocyte sedimentation rate (ESR), D-dimer, myoglobin, T‐pro brain natriuretic peptide (T‐pro‐BNP) and urea nitrogen (BUN) (all P<0.05).
Forty-six patients were classified as having mild anaemia, whereas 29 and 4 patients were classified as having moderate and severe anaemia, respectively. There was no significant difference in the proportion of severe patients or in mortality between the anaemia subtypes. However, severity of anaemia was “positively and strongly” associated with inflammatory responses and also positively associated with coagulation disorders, while no significant relationship with organ injuries was observed.
In univariate analysis, baseline data including age ≥60 years, anaemia, any comorbidities, hypertension, CVD, COPD, and laboratory indices containing CRP ≥10 mg/L, lactate dehydrogenase (LDH) ≥250 U/L, D-dimer ≥0.5 mg/L and creatinine ≥133 μmol/L were significantly associated with greater disease severity in patients with COVID-19. Anaemia remained significant as an independent risk factor for patients with severe COVID-19 in the multivariable analysis, even after adjusting for baseline data (OR: 3.47, 95%CI: 1.02-11.75, P=0.046) and laboratory indexes (OR: 3.77, 95%CI: 1.33-10.71, P=0.013).
Three patients died in the severe COVID-19 group (15%) compared to none in the non-severe group. The authors noted there was an “insignificant relationship” between anaemia and overall mortality in univariate regression analysis (P=0.996), “possibly because of the limited death toll in our cohort.”
The authors said that in their study, the prevalence of anaemia in hospitalised COVID-19 patients was up to 35.5%, which was “much higher” than a previous report that had found the frequency of anaemia in COVID-19 patients to be 15%. “Due to the limited literature on anaemia among COVID-19 patients, the accurate prevalence…remains unclear,” they said.
The authors also pointed out that as anaemia and low haemoglobin could decrease oxygen delivery, it is possible that COVID-19 patients are more susceptible to severe illness due to worse pulmonary function and poor tissue oxygenation. However, there was a lack of significant differences in lung function-related parameters between anaemic and non-anaemic patients in this particular study, but the authors noted that those with moderate-to-severe anaemia were more likely to present with dyspnea symptoms and lower levels of PaO2 and SaO2 than patients with mild anaemia.
This study also found that myocardial injury and renal dysfunction were more remarkable in patients with anaemia, possibly due to a progressive reduction in blood oxygen content and limited tissue oxygen delivery, the authors said.
In terms of limitations, researchers highlighted the small number of patients (20) in the study who had severe COVID-19. They also cautioned that the diagnosis of anaemia was made based on the levels of haemoglobin on admission, but “the exact cause and duration of anaemia remained unclear. Thus, it is difficult to verify whether SARS-CoV-2 has a direct role in anaemia, as well as if patients have anemia of chronic disease.”