COVID-19 convalescent plasma as long-term therapy in immunodeficient patients?

Abstract

Objectives The patients with hematological malignancies are a vulnerable group to COVID-19, due to the immunodeficiency resulting from the underlying disease and oncological treatment that significantly impair cellular and humoral immunity. Here we report on a beneficial impact of a passive immunotherapy with convalescent plasma to treat a prolonged, active COVID-19 infection in a patient with a history of nasopharyngeal diffuse large B-cell lymphoma treated with the therapy inducing substantial impairment of particularly humoral arm of immune system. The specific aim was to quantify SARS-CoV2 neutralizing antibodies in a patient plasma during the course of therapy. Materials and methods Besides the standard of care treatment and monitoring, neutralizing antibody titers in patient's serum samples, calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human), were quantified in a time-dependent manner. During the immunotherapy period peripheral blood flow cytometry immunophenotyping was conducted to characterize lymphocyte subpopulations. Results The waves of clinical improvements and worsening coincided with transfused neutralizing antibodies rises and drops in the patient's systemic circulation, proving their contribution in controlling the disease progress. Besides the patient's lack of own humoral immune system, immunophenotyping analysis revealed also the reduced level of helper T-lymphocytes and immune exhaustion of monocytes. Conclusion Therapeutic approach based on convalescent plasma transfusion transformed a prolonged, active COVID-19 infection into a manageable chronic disease.

Is Better Standardization of Therapeutic Antibody Quality in Emerging Diseases Epidemics Possible?

“…The first patient was diagnosed with nasopharyngeal diffuse large C-cell lymphoma and treated with R-CHOP/R-DHAP chemotherapy protocols (containing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone/rituximab, dexamethasone, cytarabine and cisplatin), followed by autologous stem cell transplantation, radiotherapy of Waldeyer’s ring, and finally maintenance therapy with the anti-CD-20 monoclonal antibody rituximab. At the start of CCP therapy a nasopharyngeal swab showed persistent RT-PCR positivity for SARS-CoV-2 for 45 days and he had a fever, respiratory insufficiency and lung infiltrates ( 28 ). The second patient had history of chronic lymphocytic leukaemia and was treated with rituximab and bendamustine.…”

Collection of Monoclonal Antibodies Targeting SARS-CoV-2 Proteins

“…SARS-CoV-2 viruses used for infection of ACE-2 transfected HEK 293T cells were USA-WA1/2020 (NR-52281, here named as WT1), obtained from BEI resources; B.1.1.7 (Alpha) and B.1.617.2 (Delta) strains, isolated from oropharyngeal swabs and B.1.351 (Beta), kindly provided by Dr. Alex Sigal (Nelson R Mandela School of Medicine, UKZN). SARS-CoV-2 virus used for infection of Vero E6 cells was a SARS-CoV-2/297/20 Zagreb (here named as WT2), isolate derived from a positively tested nasopharyngeal swab in Zagreb, Croatia (GISAID database ID: EPI_ISL_451934) passage 5 [10,11] or 0707*149 (B.1.617.2, Delta) passage 3 isolated from a nasopharyngeal swab. All virus stocks were propagated (four passages) and tittered on Vero E6 cells.…”

Compassionate mesenchymal stem cell treatment in a severe COVID-19 patient: a case report

“…The plasma was obtained in the Croatian Institute of Transfusion Medicine from a healthy donor with a documented history of SARS-CoV-2 infection who had been asymptomatic for ≥28 days and was specified eligible according to standard blood donor criteria. SARS-CoV-2 neutralizing antibodies in CCP were quantified by infective-virus neutralization assay, using a reference calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human) (NIBSC code 20/136, NIBSC, Potters Bar, UK), so the titer is expressed in international units per milliliter (IU/mL) ( 4 ). The volume of the CCP dose used for therapy was 200 mL, and the titer of neutralizing antibodies was 242 IU/mL.…”