COVID-19-associated anemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

Synonyms and keywords: Hemoglobin changes in COVID 19, anemia in COVID 19, effects on erythropoiesis in COVID 19

Overview

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2, which caused a respiratory illness outbreak that was first detected in Wuhan, China. Anemia in general is defined as a hemoglobin level of less than 13 gm/dL in men and less than 12 gm/dL in women by the World Health Organization (WHO). Although anemia is not a common finding in patients with COVID-19 infection, decrease in hemoglobin in patients with severe COVID-19 infection has been reported. The pathophysiology of decrease in hemoglobin in patients with COVID-19 infection are hypothetically affected erythropoiesis due to inflammation during COVID-19 infection which leads to decrease in hemoglobin.

Historical Perspective

• Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2, which caused a respiratory illness outbreak that was first detected in Wuhan, China.
• On January 30, 2020, the outbreak was declared a Public Health Emergency of International Concern.
• On March 12, 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO).

Classification

• Anemia, in general, is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
• The following is the classification of anemia in general by red blood cell size with mean corpuscular volume (MCV):
  • Macrocytic anemia (MCV>100)
  • Normocytic anemia (80<MCV<100)
    • High reticulocyte count
    • Low reticulocyte count
  • Microcytic anemia (MCV<80)

Here is a schematic representation of how to consider anemia with MCV as the starting point:

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Pathophysiology

The pathophysiology of decrease in hemoglobin and rarity of anemia in patients with COVID-19 infection are as the followings:

• Erythropoiesis may be affected by inflammation during COVID-19 infection which leads to decrease in hemoglobin.
• Anemia is not a common finding probably due to the compensation of erythrocyte proliferation caused by pneumonia-induced hypoxia and the long life span of erythrocytes.

Causes

• Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called SARS-CoV-2 is the cause of COVID-19-associated-anemia.

Differentiating COVID-19-associated Anemia from other Diseases

• Differential diagnosis of anemia in general may include: Iron deficiency anemia, thalassemia, sideroblastic anemia, anemia of inflammation, aplastic anemia, hypothyroidism, liver disease, renal disease, reticulocytosis, thyroid disease, vitamin B12 and folate deficiency, chemotherapy, myelodysplastic syndrome, acute onset hemolysis or blood loss.

For complete differential diagnosis of anemia please click here.

Epidemiology and Demographics

• Anemia is a very rare complication of COVID-19.
• There is no new update about COVID-19 associated anemia.

Risk Factors

• There is no associated risk factor for COVID-19 associated anemia.

Screening

• There is insufficient evidence to recommend routine screening for anemia in COVID-19 infection.

Natural History, Complications, and Prognosis

• Although anemia is not a common finding in patients with COVID-19 infection, but decrease in hemoglobin in patients with severe COVID-19 infection has been reported.
• The median hemoglobin is lower in patients with severe COVID-19 (12.8 gm/dL) compared to patients with non-severe infection (13.5 gm/dL).
• Decrease in hemoglobin is seen more in critically ill patients with severe COVID-19 infection.

Diagnosis

Diagnostic Study of Choice

• The diagnostic study of choice for anemia is complete blood count (CBC).
• Anemia, in general, is defined as a hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women by the World Health Organization (WHO).
• The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).

History and Symptoms

• There is insufficient information about the symptoms of COVID-19-associated-anemia.
• Patients with anemia in general should be asked about:
  • Blood loss  
  • Duration of the anemia  
  • Any associated features  
  • Infection
  • Cancer
  • Comorbidities that cause anemia (such as renal failure, rheumatoid arthritis, and inflammatory bowel disease)
  • Past medical history
  • Patient’s ethnicity may influence the differential  
  • Family history
  • Drug history (aspirin and NSAIDs)

Physical Examination

• There is insufficient information about the signs found on physical examination of COVID-19-associated-anemia.
• The physical examination in patients with anemia in general may include checking for:
  • Pallor of the conjunctiva 
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Bone tenderness
  • Petechiae
  • Ecchymose  

Laboratory Findings

• Complete blood count (CBC):
  • The median hemoglobin is lower in patients with severe COVID-19 (12.8 g/dL) compared to patients with non-severe infection (13.5 g/dL).
• Peripheral blood smear:
  • Maybe helpful if there is a suspicion of other causes of anemia. However, there is insufficient evidence recommending routine peripheral blood smear in COVID-19 patients.
• Reticulocyte count: 
  • Maybe helpful if there is a suspicion of other causes of anemia.
• Red cell indices: May be helpful if there is a suspicion of other causes of anemia which includes:
  • MCV
  • Mean corpuscular hemoglobin concentration (MCHC)
  • Mean corpuscular hemoglobin (MCH)
• To view the laboratory findings on COVID-19, click here.

Electrocardiogram

• There are no ECG findings associated with COVID-19-associated anemia.
• However, the following findings may be seen on ECG in patients with anemia:
  • Tachycardia, ST depression, T wave changes (T wave flattening and inversion), and QRS abnormalities (indicating LVH and cardiac enlargement).
• To view the electrocardiogram findings on COVID-19, click here.

X-ray

• There are no x-ray findings associated with COVID-19 associated anemia.
• To view X-ray findings of COVID-19 ,click here.
  

Echocardiography or Ultrasound

• There are no echocardiography/ultrasound findings associated with COVID-19-associated anemia.
• To view the echocardiographic findings on COVID-19, click here.
  

CT scan

• There are no CT scan findings associated with COVID-19 associated-anemia.
• To view the CT scan findings on COVID-19, click here.

MRI

• There are no MRI findings associated with COVID-19 associated-anemia.
• To view the MRI findings on COVID-19, click here.
  

Other Imaging Findings

• There are no other imaging findings associated with COVID-19 associated-anemia.
• To view other imaging findings on COVID-19, click here.
  

Other Diagnostic Studies

• Bone marrow examination: 
  • May be helpful if there is a suspicion of other causes of anemia. However, there is insufficient evidence recommending routine bone marrow examination in COVID-19 patients.
• Cytogenetic and molecular tests: 
  • May be helpful if there is a suspicion of other causes of anemia. However, there is insufficient evidence recommending routine cytogenetic and molecular in COVID-19 patients.
• To view other diagnostic studies for COVID-19, click here.
  

Treatment

Medical Therapy

• Treatment of anemia in general depends on the cause of anemia.
• No specific treatment has been reported for COVID-19-associated-anemia.

Surgery

• Surgery is not a treatment option for patients with COVID-19 associated anemia.

Primary Prevention

• There are no established measures for the primary prevention of COVID-19 associated anemia.

Secondary Prevention

• Minimal amount of blood should be drawn for blood tests and only clinically necessary tests should be ordered in order to prevent aggregation of COVID-19 associated anemia.