How to manage leukopenia in patients with long COVID?

From the Guidelines

Managing leukopenia in patients with long COVID requires a careful and individualized approach, prioritizing monitoring and targeted interventions to minimize morbidity, mortality, and improve quality of life. The management strategy should start with establishing baseline complete blood counts and regular monitoring to track white blood cell levels 1. Given the potential for long COVID to impact quality of life significantly, as suggested by the need for assessments that include symptom severity and impact on quality of life 1, treatment should focus on addressing underlying causes such as inflammation and potential autoimmune mechanisms.

Key considerations in management include:

• Addressing underlying inflammation, potentially with anti-inflammatory medications, though specific guidance on this for long COVID is still evolving.
• Nutritional support to enhance immune function, focusing on foods rich in protein, zinc, vitamin B12, and folate.
• Avoidance of bone marrow suppressant medications when possible.
• Appropriate vaccinations and infection prevention measures to reduce the risk of complications.
• Treatment of any co-infections, which can exacerbate leukopenia.

In severe cases, where the absolute neutrophil count is significantly low, interventions such as granulocyte colony-stimulating factors may be considered to stimulate white blood cell production. However, the specific application of such treatments in the context of long COVID would need to be guided by the most recent clinical evidence and expert consensus, considering the unique pathophysiology of long COVID. Regular reassessment of blood counts during active management is crucial to guide treatment adjustments and ensure the best possible outcomes for patients.

From the FDA Drug Label

INDICATIONS AND USAGE ZARXIO is a leukocyte growth factor indicated to • Reduce the incidence and duration of sequelae of severe neutropenia (e.g. ‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia (1.5)

The management of leukopenia in patients with long COVID is not directly addressed in the provided drug labels. However, filgrastim is indicated to reduce the incidence and duration of sequelae of severe neutropenia in symptomatic patients with congenital, cyclic, or idiopathic neutropenia 2.

• Key points:
  • Filgrastim may be considered for patients with long COVID who have leukopenia, but only if they have a condition that is similar to the approved indications, such as congenital, cyclic, or idiopathic neutropenia.
  • The recommended starting dose for patients with congenital neutropenia is 6 mcg/kg subcutaneous injection twice daily 2.
  • The recommended starting dose for patients with cyclic or idiopathic neutropenia is 5 mcg/kg subcutaneous injection daily 2.
• Important consideration: The use of filgrastim in patients with long COVID and leukopenia is not explicitly approved, and the decision to use it should be made on a case-by-case basis, considering the individual patient's condition and medical history.

From the Research

Management of Leukopenia in Long COVID Patients

To manage leukopenia in patients with long COVID, it is essential to understand the underlying causes and correlations with inflammatory markers.

• A study published in the Journal of community hospital internal medicine perspectives 3 found that patients with long COVID symptoms had higher Neutrophil to lymphocyte ratio (NLR) values and more severe lymphopenia.
• Another study published in IEEE access: practical innovations, open solutions 4 developed a scoring system using complete blood count (CBC) parameters, including white blood cell count, to predict disease severity in COVID-19 patients.

Correlations with Inflammatory Markers

Research has shown that inflammatory markers, such as C-reactive protein (CRP), can be associated with long COVID symptoms 3.

• A cross-sectional study published in the Journal of community hospital internal medicine perspectives 3 found correlations between CBC markers, including red blood cell (RBC), white blood cell (WBC), and NLR, and long COVID symptoms at a 6-month follow-up.
• The study suggested that utilizing available data like CBC can help predict upcoming symptoms of previously hospitalized patients and inform further measures like rehabilitation.

Latent Infections and Long COVID

Emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may contribute to the complexity of long COVID 5.

• A review published in the Journal of clinical medicine 5 highlighted the potential involvement of latent viral infections in long COVID and examined whether these infections play an independent role or act synergistically with other factors.
• The review suggested that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, may reduce long COVID risk by preventing viral reactivation.

Clinical Presentation and Mortality

Studies have investigated the clinical presentation and mortality rates of long COVID patients.

• A study published in JMIR public health and surveillance 6 found that people presenting to primary care after hospital infection were more likely to be men, more socioeconomically deprived, and with higher multimorbidity scores than those presenting after an index community infection.
• The study also found that all-cause mortality in people with long COVID was associated with increasing age, male sex, and higher multimorbidity score, while vaccination was associated with reduced odds of mortality.