key: cord-0702187-1vhbbz92
authors: Ordaya, Eloy E.; Abu Saleh, Omar M.; Stubbs, James R.; Joyner, Michael J.
title: Vax-Plasma in Patients With Refractory COVID-19
date: 2021-11-12
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2021.11.001
sha: bc1e4ccd526d785ba59b5b1423816ca88bfde3fb
doc_id: 702187
cord_uid: 1vhbbz92

nan

To the editor: Convalescent plasma (CP) therapy uses neutralizing antibodies harvested from recovered patients to treat viral infections, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Influenza A. 1 The emerging data from randomized controlled trials and observational studies suggestsconsistent with historical precedent -that CP therapy has limited efficacy in severely ill patients with coronavirus disease 2019 (COVID-19) treated late in the disease course. However, early treatment with high titer CP shows signs of efficacy. 2 Additionally, CP use in immunocompromised hosts unable to generate endogenous antibodies suggest a mortality benefit and rapid clinical improvement. 3, 4 One group of patients that benefit from CP therapy are those with primary or secondary B-cell deficiencies with a high risk for severe COVID-19 due to their reduced ability to produce neutralizing antibodies. 5, 6 These patients can also have prolonged refractory COVID-19 that can last many months and include the generation of novel viral variants. In this context, Vax-plasma is the CP from patients who have recovered from natural infection and been subsequently vaccinated. It can have 10 -100 times higher antibody titers than standard high-titer CP with broad coverage of known COVID-19 variants. 7 Herein, we present our first experience using Vax-plasma in an immunocompromised patient with refractory COVID-19. (Table) .

During his last hospitalization in the summer of 2021, the patient presented again with fever, hypoxia, and persistent pulmonary infiltrates (Figure C-D) . He received remdesivir, corticosteroids, and two units of high-titer CP. Semi-quantitative detection of total antibodies against SARS-CoV-2 Spike protein (Roche Elecsys Anti-SARS-CoV-2 S assay) resulted 2.9 U/mL after the first infusion of CPT and 4.1 U/mL after the second unit. IMMUNO-COV™ SARS-Cov-2 neutralizing antibody test was negative. As he persisted with hypoxia, Vax-plasma was administered. After the first infusion, the semiquantitative detection of total antibodies against SARS-CoV-2 Spike antibody was repeated and resulted >250 (Roche Elecsys Anti-SARS-CoV-2 S assay). After the second dose the following day, the semi-quantitative detection of total antibodies resulted >250, Anti-and IMMUNO-COV™ SARS-CoV-2 neutralizing antibody was positive (level = 286). No adverse side effects were reported. The patient improved progressively, and on dismissal seven days later, he was afebrile and not hypoxic. On follow-up, he remained afebrile, with normal oximetry, and imaging showed almost complete resolution of pulmonary infiltrates (Figure E-F) . He also had a negative SARS-CoV-2 RNA test one month after his last hospitalization and 305 days after his first positive test. He has subsequently received monthly outpatient infusions of Vax-J o u r n a l P r e -p r o o f plasma, and after ten weeks of follow-up, the patient has not been admitted to the hospital.

To our knowledge, this is the first report of Vax-plasma treatment in a COVID-19 patient unable to mount normal antibody responses to the disease. Notably, the serum neutralizing antibody response from individuals who have been infected is enhanced after receiving an mRNA vaccine and could effectively neutralize an array of COVID-19 variants. 7,8 In conclusion, the use of Vax-plasma is a promising therapy that can be included in the treatment and prevention of COVID-19 in immunocompromised patients.

Franchini 

The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory metaanalysis

The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis

use of convalescent plasma in COVID-19 patients with immunosuppression

SARS-CoV-2 Spike Ab: SARS-CoV-2 spike glycoprotein antibody (Roche Elecsys Anti-SARS-CoV-2 S Reagent assay from Roche Diagnostics), SARS-CoV-2 Neutralizing Ab: IMMUNOCOV. ND: no data. a Patients received initially between 5 to 10 days of dexamethasone but then PDN at different doses after the diagnosis of COP. b Admission complicated by aspiration pneumonia and cryptogenic organizing pneumonia (COP) starting prednisone (PDN) 20 mg per day, and then receiving progressive tapering dose. c SARS-CoV-2 nucleocapsid antibody was negative before receiving convalescent plasma (CP) and then turned positive after receiving 2 units of high-titer CP. d Patient required intubation with SARS-CoV-2 positive from nasopharynx and bronchoalveolar lavage samples. e SARS-CoV-2 spike protein antibody test results after receiving the first and second unit of high-titer convalescent plasma. f SARS-CoV-2 spike protein antibody test results after receiving the first and second unit of super high-titer convalescent plasma (Vax-plasma). g SARS-CoV-2 neutralizing antibodies after receiving two units of high-titer convalescent plasma