COVID-19-associated lymphopenia

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

Synonyms and keywords:

Overview

Coronavirus disease 2019 (COVID-19) has been considered as a global pandemic since its first emergence in Wuhan, China. On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. There is no established system for the classification regarding COVID-19 related lymphopenia. four hypothetical mechanisms regarding lymphopenia are Direct infection of Lymphocyte, direct destroying of lymphocytic organs, inflammatory cytokines such as TNFɑ, IL-6, Lymphocyte inhibition,

Historical Perspective

• Coronavirus disease 2019 (COVID-19) has been considered as a global pandemic since its first emergence in Wuhan,China.

• On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
• Since the first descriptive study lymphocyte count has been a marker of interest.

Classification

There is no established system for the classification regarding COVID-19 related lymphopenia.

Pathophysiology

• There are four hypothetical mechanisms regarding lymphopenia
  • Direct infection of Lymphocytes
  • Direct destroying lymphatic organs
  • Inflammatory cytokines such as TNF ɑ, IL-6 , etc inducing lymphopenia
  • Inhibition of lymphocytes by metabolic molecules such as hyperlactic acidemia

Causes

The SARS-CoV-2 (COVID-19) viral infection is the known cause of lymphopenia in COVID-19 patients. To read more click here

Differentiating COVID-19 related Lymphocytopenia from other Diseases

COVID-19 related Lymphocytopenia starts acutely in the course of the disease, with other manifestations of the disease. Lymphocytopenia, is associated with corticosteroid use, infections with HIV and other viral, bacterial, and fungal agents, Hodgkin's disease, leukemia, malnutrition, systemic lupus erythematosus, high stress levels, whole body radiation, rheumatoid arthritis, and iatrogenic conditions.

In alphabetical order.

• After influenza
• After snakebite
• Anesthesia
• Antibody deficiency syndrome
• Aplastic Anemia
• Banti's Syndrome
• Burns
• Congenital immune deficiency
• Cushing's Disease
• Dermatomyositis
• Drugs, toxins
• Exudative enteropathy
• Felty's Syndrome
• Heavy exercise
• HIV
• Hodgkin's Lymphoma
• Inflammatory Bowel Disease
• Lymphocyte tuberculosis
• Measles
• Paroxysmal nocturnal hemoglobinuria
• Polycythemia
• Postoperative
• Pregnancy
• Sarcoidosis
• Scarlet Fever
• Secondary hypersplenism
• Single non-Hodgkin's lymphomas
• Surgery
• Systemic Lupus Erythematosus
• Trauma
• Tuberculosis
• Uremia
• Whipple's Disease
• Zinc deficiency

Epidemiology and Demographics

• The incidence of the Coronavirus Disease 2019 (COVID-19) as of June 28, 2020 is approximately 9,843,073 cases worldwide with 495,760 deaths.
• Patients of all age groups may develop COVID-19. However, the elderly population and immunocompromised individuals are more likely to develop severe cases of COVID-19.

Risk Factors

People of any age with certain underlying medical conditions are at increased risk for severe illness from COVID-19. These medical conditions include:

• Chronic kidney disease
• Chronic obstructive pulmonary disease
• Immunocompromised state (weakened immune system) from solid organ transplant
• Obesity (body mass index [BMI] of 30 or higher)
• Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
• Sickle cell disease
• Type 2 diabetes mellitus

Screening

• Lymphopenia on admission has been associated with predicting the severity of clinical outcomes. Approximately, a three-fold increase in severity has been associated with lymphopenia on admission.
• A routine CBC with differential can be used for monitoring and predicting disease progression and severity in patients.

Natural History, Complications, and Prognosis

• Lymphopenia is the most common laboratory finding in COVID-19, and is found in as many as 83% of hospitalized patients.
• Lymphopenia is lymphocyte count of less than 1.5 × 109/L. It is associated with a 3-fold increased risk of severe COVID-19 infection.
• Patients with lymphopenia on admission have been associated with poor prognostic outcomes. Recent studies have shown that 85% of severely ill patients have lymphopenia. Futhermore, patients who have died from COVID-19 infection showed significantly lower lymphocyte level than survivors.
• Common hematologic complications of coronavirus also include neutrophilia and thrombocytosis.

Diagnosis

Diagnostic Choice of Study

Lymphopenia refers to a count of less than 1,000 lymphocytes per microliter of blood in adults, or less than 3,000 lymphocytes per microliter of blood in children. The following tests are used to diagnose lymphopenia:

• Complete Blood test
• Flow cytometry

History and Symptoms

Lymphopenia as a result of COVID-19 can present with different symptoms. People with COVID-19 have had a wide range of symptoms reported – ranging from mild symptoms to severe illness. Symptoms may appear 2-14 days after exposure to the virus. People with these symptoms may have COVID-19:

• Fever or chills
• Cough
• Shortness of breath or difficulty breathing
• Fatigue
• Muscle or body aches
• Headache
• New loss of taste or smell
• Sore throat
• Congestion or runny nose
• Nausea or vomiting
• Diarrhea

Physical Examination

• There are no physical findings associated with lymphopenia.
• However patients with significant lymphopenia can show signs of the associated disorder, in this case COVID-19 symptoms.

Laboratory findings

• Lymphocyte count on CBC with differential is less than 1.5x109/L is potentially associated with severe outcomes.
• Peripheral blood smear- This maybe helpful, however there is insufficient evidence recommending routine peripheral blood smear in COVID-19 patients.

Electrocardiogram

There are no ECG findings associated with COVID-19 associated lymphopenia.

X-ray

There are no X-ray findings associated with COVID-19 associated lymphopenia.

Echocardiography or Ultrasound

There are no echocardiography or ultrasound findings associated with COVID-19 associated lymphopenia.

CT Scan

There are no CT scan findings associated with COVID-19 associated lymphopenia.

MRI

There are no MRI findings associated with COVID-19 associated lymphopenia.

Other imaging findings

There are no other imaging findings associated with COVID-19 associated lymphopenia.

Other Diagnostic studies

• Bone marrow biopsy, although not recommended may be helpful if there is suspision of other disorders that can cause lymphopenia , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients.

Treatment

Medical therapy

Immune-Based Therapy:

• There are insufficient data to recommend either for or against the use of COVID-19 convalescent plasma or SARS-CoV-2 immune globulins for the treatment of COVID-19.

The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial. This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.

• There are insufficient data to recommend either for or against the use of the following agents for the treatment of COVID-19:
  • Interleukin-1 inhibitors (e.g., anakinra)
  • Interleukin-6 inhibitors (e.g., sarilumab, siltuximab, tocilizumab)

Except in the context of a clinical trial, the Panel recommends against the use of other immunomodulators, such as: Interferons, because of the lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity. Janus kinase inhibitors (e.g., baricitinib), because of their broad immunosuppressive effect.

References

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