Some patients with malignant tumors and autoimmune diseases are prescribed rituximab. Rituximab is a B-cell monoclonal antibody that depletes B cells.
Patients who receive rituximab are prone to contracting viral infections. French scientists described lingering forms of SARS-CoV-2 illness with persistent fever and poor breathing in two patients who received rituximab to treat autoimmune diseases.
With SARS-CoV-2 infection, more than 90% of non-immunocompromised patients develop IgM and IgG antibodies within the first 14 days. However, in patients receiving rituximab, IgG to SARS-CoV-2 was not produced. Scientists have suggested that the cause of prolonged COVID-19 is the incomplete elimination of SARS-CoV-2 due to impaired or delayed antibody production.
Two Cases of Lingering SARS-Cov-2 Pneumonia During Treatment With Rituximab
The first patient is a 65-year-old male who received rituximab for 2 years to treat optic neuromyelitis. The man reported flu-like symptoms within 10 days, and a PCR test confirmed SARS-CoV-2 infection. 7 days after the symptoms disappeared, the patient developed fever, weakness, weight loss, muscle and joint pain, and diarrhea. The patient was admitted to the hospital on the 32nd day. Computed tomography of the chest 32 days after symptoms showed bilateral pneumonia with 10–25% lesion. Nasopharyngeal swab tested negative for SARS-CoV-2. Despite therapy with broad-spectrum antibiotics, the patient’s condition worsened – the patient had persistent fever and increased oxygen demand. Bronchoalveolar lavage on the 39th day revealed a high viral load. PCR test revealed SARS-CoV-2 in the blood serum. The patient is treated with intravenous methylprednisolone. On the 42nd day, the patient was transferred to the intensive care unit due to respiratory failure – computed tomography showed more than 50% lung involvement. The patient received mechanical ventilation for 17 days and corticosteroid therapy for 27 days, which improved his condition. On day 81, the patient returned home. SARS-CoV-2 IgA peaked after more than 40 days of illness, but IgG remained undetectable even on day 68.
The second patient is a 46-year-old male who received rituximab for 2 years to treat severe rheumatoid arthritis. The man was diagnosed with SARS-CoV-2 infection. Due to persistent fever above 39 ° C and significant weight loss, the patient was admitted to the hospital 34 days after symptom onset. Computed tomography of the chest showed pneumonia with 10–25% lesions. On day 34, the SARS-CoV-2 PCR test was negative in a nasopharyngeal swab, but bronchoalveolar lavage showed a high viral load. Pseudomonas aeruginosa was found in lung cells. Treatment is with intravenous dexamethasone and ceftazidime. After 7 days, the patient still had a fever above 40°C and required supplemental oxygen. On the 45th day, PCR for SARS-CoV-2 gave a positive result in blood plasma. The lung damage reached 25-50%. The patient received remdesivir for 56 days and twice-convalescent plasma. After that, the patient’s temperature immediately dropped. He was discharged on the 56th day. On the 84th day, the patient had a fever. IgA was detectable on day 35, but IgG levels remained undetectable on day 43 and 5 months after the onset of COVID-19.
Immunostimulation With Interferon-γ For Protracted Pneumonia SARS-Cov-2
Sometimes convalescent plasma does not have a therapeutic effect. That was the case with a 68-year-old female patient from another French study.
The patient received long-term rituximab for the treatment of rheumatoid arthritis. Her medical history includes Sjogren’s syndrome, renal failure, and polyneuropathy. 14 days after the onset of symptoms and the diagnosis of COVID-19, the patient was prescribed dexamethasone (15 days). 20 days after the start of symptoms and diagnosis of COVID-19, the patient was admitted to the intensive care unit with respiratory distress syndrome requiring high-flux oxygen therapy. The PCR test detected SARS-CoV-2 in both bronchoalveolar lavage and serum. In addition to severe lymphopenia with a complete absence of B cells, the patient lacked IgG to SARS-CoV-2, the functions of cytotoxic T cells were impaired, and low levels of expression of the central histocompatibility complex receptors on the surface of monocytes (HLA-DR) were observed. The primary function of HLA-DR is to present foreign compounds to the immune system for the body to produce antibodies.
On days 22 and 23, after the onset of symptoms of COVID-19, the patient received convalescent plasma. However, the treatment did not help, and the degree of bilateral lung damage continued to increase – from 30 to 70% in 6 days. On days 28 and 30, the patient received convalescent plasma again. However, on day 32, her condition continued to deteriorate, therapy with interferon-gamma (IFN-γ) was prescribed of100 mcg per day subcutaneously for 3 days.
The introduction of IFN-γ improved the patient’s condition within a few days. In addition, mHLA-DR expression and lymphocyte count increased, and nasopharyngeal swabs and blood were negative for SARS-CoV-2. The patient did not require mechanical ventilation. On the 41st day, the patient left the intensive care unit and returned home on the 54th day. During treatment with interferon-γ, the patient complained only of mild joint pain.
Output
Immunotherapy with interferon-gamma improved the antiviral response by increasing the cytotoxicity of T cells and the expression of MHC molecules on the cell surface of monocytes and infected cells. IFN-γ treatment prevented the need for mechanical ventilation.
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References
- Immunostimulation with interferon-γ in protracted SARS-CoV-2 pneumonia
- Protracted SARS ‐ CoV ‐ 2 pneumonia with rituximab treatment: About two cases
