COVID-19-associated neutrophilia

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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:WBC changes in COVID-19, SARS-COV2 related neutrophilia

Overview

Coronavirus disease 2019 (COVID-19) first emerged in Wuhan,China in late 2019. 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 associated neutrophilia. Research suggests COVID-19 associated neutrophilia could be the cause of the severe symptoms of COVID-19, including acute respiratory distress syndrome (ARDS) and can be linked to the Neutrophil Extracellular Traps (NETs). Acute respiratory distress syndrome (ARDS), pulmonary inflammation, thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be a result of the action of neutrophils. When neutrophils detect pathogens, they can expel their DNA in a web laced with toxic enzymes (called a Neutrophil Extracellular Trap) to attack them. These NETs capture and digest the unwanted pathogen. However, in cases of ARDS, (COVID-19 manifestation) they cause damage to the lungs and other organs. People of any age with certain underlying medical conditions are at increased risk for severe illness from COVID-19. Recent studies have shown the association of a high neutrophil-to-lymphocyte ratio (NLR) to severe forms of COVID-19 disease.

Historical Perspective

• Coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China in late 2019.

• On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.

Classification

• There is no established system for the classification regarding COVID-19 associated neutrophilia.

Pathophysiology

• Study suggests COVID-19 associated neutrophilia could be the cause of the severe symptoms of COVID-19, including acute respiratory distress syndrome (ARDS). It can be linked to the Neutrophil Extracellular Traps (NETs).
• Acute respiratory distress syndrome (ARDS), pulmonary inflammation, thick mucus secretions in the airways, extensive lung damage, and blood clots are suggested to be a result of the action of neutrophils. When neutrophils detect pathogens, they can expel their DNA in a web laced with toxic enzymes (Neutrophil Extracellular Trap) to attack them.
• These NETs capture and digest the unwanted pathogen, however, in cases of ARDS (COVID-19 manifestation) they cause damage to the lungs and other organs.
• Neutrophilia as an indicator for severe disease:
  • Recent studies have shown the association of a high neutrophil-to-lymphocyte ratio (NLR) to severe forms of COVID-19 disease.
  • NLR >4 on admission has been linked to ICU admission.
  • COVID-19 patients with severe disease presentation had a higher NLR on admission compared to patients with a milder COVID-19 disease presentation.

Causes

• The SARS-CoV-2 COVID-19 viral infection is the known cause of neutrophilia associated disease in infected patients.

Differentiating COVID-19 related Neutrophilia from other Diseases

• COVID-19 related neutrophilia starts acutely in the course of the disease, with other manifestations of the disease. Neutrophilia can occur in the following conditions:
  • Acute infections
    • Bacteria - Staphyloccoci, streptococci, meningococci
    • Virus- Varicella, herpes zoster
    • Fungi- Candida, coccidioides
  • Non-infectious inflammation
    • Rheumatic fever
    • Acute glomerulonephritis
    • Collagen-vascular diseases
    • Diabetic ketoacidosis

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 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

• A high neutrophil-to-lymphocyte ratio has been linked to ICU admission. A routine complete blood count (CBC) test should be done in COVID-19 patients for early detection.

Natural History, Complications, and Prognosis

• Common hematologic complications of coronavirus include lymphopenia, neutrophilia and thrombocytosis.
• The pathogenesis of the cytokine storm associated with neutrophilia in COVID-19 patients is unclear.
• It has, however, been associated with poor outcomes in patients. The neutrophil-to-lymphocyte ratio has been identified as an independent risk factor for severe disease in COVID-19 patients.

Diagnosis

Diagnostic study of Choice

• Peripheral white blood cell count on a CBC with differential test
• Neutrophil-lymphocyte ratio
• C-reactive protein
• Erythrocyte sedimentation rate

History and Symptoms

• Neutrophilia 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 (SOB) 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 COVID-19 associated neutrophilia.

• For COVID-19 Physical examination click here.

Laboratory findings

• Increased neutrophils on CBC
• Increased inflammatory markers such as IL-6, CRP
• For more information about COVID-19 related laboratory findings please click here.

Electrocardiogram

• There are no ECG findings associated with COVID-19 associated neutrophilia.
• To view the electrocardiogram findings on COVID-19, click here.

X-ray

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

Echocardiography or Ultrasound

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

CT Scan

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

MRI

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

Other imaging findings

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

• To view other imaging findings on COVID-19, click here.

Other Diagnostic studies

• Bone marrow biopsy, although not recommended may be helpful if there is suspicion of other disorders that can cause neutrophilia , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients.
• To view other diagnostic studies for COVID-19, click here.

Treatment

Medical therapy

Immune-Based Therapy:

• There is 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 the 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.

Surgery

• Surgical intervention is not recommended for the management of COVID-19 associated neutrophilia.

Primary Prevention

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

Secondary Prevention

• There are no established measures for the secondary prevention of COVID-19 associated neutrophilia.