Demographic and clinical Characteristics of COVID-19 patients
A total of 375 patients were admitted to hospital, and 153 cases were excluded due to having negative reverse-transcription polymerase chain reaction (RT-PCR) results (n=144), age<18 (n=3), missing data on haemoglobin levels(n=3)(Figure 1). Finally, a total of 222 cases, including 202 non-severe patients and 20 severe patients, were included in our study. Among 222 patients, 3 died. Baseline characteristics are described in Table 1. The median age of the patients was 55 years (IQR, 42-66 years); there were with 80(36.0%) male and 142(64.0%) women. Overall, 81(36.5%) patients had one or more comorbidities, of which hypertension(28.6%)was the most common one, followed by diabetes(12.2%), cardiovascular disease(CVD)(7.7%), and chronic obstructive pulmonary disease(COPD)(3.6%).The most common symptom at the onset of the illness was fever(59.5%), followed by cough(54.1%), expectoration(23.0%), weakness(18.0%), chest pain(15.3%), and dysponea (13.5%). A minority of patients initially presented with diarrhoea(9.9%), myalgia(1.8%), and pharyngula(1.4%). Based on the guideline described previously, disease severity was graded as severe or non-severe, respectively. As reported by previous studies, compared with non-severe patients, severe cases were significantly older(54 years vs 65 years,P=0.004) and significantly more likely to suffer from underlying disorders (31.7% vs 85.0%, P=0.000), such as hypertension, CVD, andCOPD.
Laboratory measurement of COVID-19 patients
Laboratory tests of COVID-19 patients were conducted at the time of admission, and the results are shown in Table2. Patients with COVID-19 presented with an inflammatory response combined with functional impairment of major organs. Differences were observed between the subgroups. Compared with non-severe patients, some indices of coagulation, cardiac, renal, and liver function,such as D-dimer,prothrombin time(PT), lactate dehydrogenase (LDH), urea nitrogen(BUN), glutamic oxiracetam transaminase(ATS), total bilirubin,were significantly elevated in severe patients(all P<0.05).Moreover, inflammatory biomarkerssuch as c-reactive protein (CRP), procalcitonin(PCT), erythrocyte sedimentation rate(ESR), and neutrophil countswere higherin severe patients than in non-severe cases. Notably, 79(35.6%) patients met the diagnostic criteria foranaemia. Consistent with previous researches, in severe patients, haemoglobin levels showed a significant decline when compared to non-severe patients (128g/L vs 111.5g/L,P=0.002). Further, significantly more patients inthe severe group met the diagnostic criteria for anaemia(32.2% vs 70.0%,P=0.001) , which is of great significance but can easily be ignored.
Comparisons between patients with anaemia and without anaemia
The diagnosis and severity of anaemia were established based on the WHO definitions[10]. Haemoglobin levels of patients with and without anaemiawere 134 g/L and 112 g/L, respectively(P=0.000)(Figure2A). In our study, the prevalence of severe illness in the anaemic group was significantly higher than that in the non-anaemicgroup (8.1% vs 17.7%, P=0.001)(Figure2B,). Tables 3 and 4 present the differences between the subgroups. Compared with patients without anaemia, patients with anaemia were older and more likely to undergo chronic kidney disease(CKD)(0.0% vs 3.8%), CVD(3.5% vs 15.2%), and COPD(0.0% vs 10.1%)(all P<0.05). Neither sex nor symptoms were significantly different between patients with anaemia and those without. In terms of laboratory testing, COVID-19 patients with anaemia were predisposed to more severe inflammatory responses, coagulation disorders, and organ injuries. More patients demonstrated elevated levels of CRP(8.5% vs 24.7%), and PCT(1.3% vs 15.6%) in theanaemic group(all P<0.05) (Figure2C,2D). Beyond that, patients with anaemia showed significantly higher levels of ESR, D-dimer, myoglobin, T-pro-BNP and BUN(all P<0.05) (Figure2E).Further, most indices of blood routine including white blood cell count(WBC), lymphocyte, neutrophils, eosinophils, red blood cell count(RBC), haematocrit, and platelet count were prominently lower in theanaemicgroup compared to the non-anaemic group(all P<0.05) (Figure 2F). Kaplan-Meier survival curve showed that patients with anaemia had lower survival rate than patients without anaemia(Log-rank test: P=0.019)( see additional file 3).
Differences between patients with anaemia in various severity
The severity of anaemia was established based on the WHO definitions[10]. Among the 222 patients in our study,46 patients were classified as having mild anaemia, whereas 29 and 4 patients were classified as having moderate and severe anaemia, respectively. Haemoglobin levels of the three groups were 116g/ L, 103g/ L, and72g/L, respectively. Compared with the mild anaemia group, patients with moderate to severe anaemiawere more likely to present with dyspnoea(24.2% vs 6.5%,P=0.025), while no significant difference was found in the age, sex, comorbidities, proportion of severe patients, and mortality between the anaemiasubtypes (As is shown in Table3, Figure2B, additional file 1). For laboratory indices, we found that the severity of anaemia was positively associated with inflammatory responses and coagulation disorders, whereas no significant relationship with organ injuries was observed. The prevalence of CRP, PCT beyond the normal range, and elevated levels of ESR and D-dimer, were prominently higher in patients with moderate to severe anaemiacompared to patients with mild anaemia(Figure2C,2D). Moreover, the absolute values of WBC, lymphocyte count(Figure2E), eosinophils, RBC, platelet count, haematocrit, SO2, and PO2 gradually and significantly decreased as theanaemia grade increased(all P<0.05).
Associations between anaemia and severe illness of COVID-19
To assess whether anaemia is a risk factors for the severe illness of COVID-19, logistic regression analysis was performed. Based on the recent studies and our statistical results, some variables among the baseline data and laboratory findings were included in the logistic regression model. As summarised in Figure3andadditional file 2, in univariate analysis, baseline data including hypertension, CVD, COPD, age≥60 years, anaemia and laboratory indices containing CRP≥10 mg/ L, LDH≥250 U/L, and D-dimer≥0.5 mg/L were significantly associated with the increased disease severity in patients with COVID-19. We further screened and selected the variables to be included in the multivariable logistic regression model. The multivariable analysis indicated that anaemia remained significant as an independent risk factor for patients with severe COVID-19, even after adjusting for baseline data(OR:5.07,95%CI:1.82-14.18,P=0.002) and laboratory indexes(OR:3.47,95%CI:1.02-11.75,P=0.046).However, anaemiashowed an insignificant relationship with the overall mortality of COVID-19 patients in univariate analysis (P=0.996), possibly because of the limited death toll in our cohort.