We also analyzed a different set of 26 CP units from LifeSouth Community Blood Centers (LSCPs) that were pre-screened with a SARS-CoV-2 spike immunoassay (Ortho-VITROS)

We also analyzed a different set of 26 CP units from LifeSouth Community Blood Centers (LSCPs) that were pre-screened with a SARS-CoV-2 spike immunoassay (Ortho-VITROS). the administered units. To obtain the full therapeutic benefits of CP immunotherapy, it will thus be important to determine the neutralizing activity in both CP units and transfusion candidates. Keywords: immunodeficiency, chronic lymphocytic leukemia, CLL, SARS-CoV-2, COVID-19, convalescent plasma, neutralizing antibodies, pneumonia, immunotherapy Graphical Abstract Open in a separate window Highlights Convalescent plasma clinically benefited a severely ill immunodeficient patient The transfer of high-titer neutralizing antibodies led to rapid clinical recovery Neutralizing activity was low in most convalescent plasmas but high in recipients Neutralizing activity should be tested in both plasma donors and recipients An immunodeficient patient with protracted COVID-19 unable to mount a humoral immune response rapidly recovered following transfusion with convalescent plasma. Honjo et?al. found that immunotherapy with high-titer neutralizing antibodies was clinically beneficial. However, since neutralizing activity of convalescent plasmas varies widely, units should be tested prior to therapy. Introduction One strategy to treat coronavirus disease 2019 (COVID-19) is to use convalescent plasma (CP) from individuals who have successfully cleared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and established humoral immunity.1 Historical evidence indicates that CP mitigates human infectious diseases,2 including those caused by the related SARS-CoV-1 (SARS) and Middle East respiratory syndrome (MERS) coronaviruses.3,4 CP therapy is widely used and was initiated as an investigational new drug (IND) by the US Food and Drug Administration (FDA) through a nationwide expanded access treatment protocol.5 Considered safe,6,7 it was approved for emergency use authorization (EUA) on August 23, 2020.8 However, as of yet there is no evidence for efficacy,9, 10, 11, 12 thus rendering this decision controversial.13 This may be because correlates of immune protection are lacking, which render the identification of appropriate convalescing donors and recipients difficult. A key component of CP is neutralizing antibodies (NAbs) that impede SARS-CoV-2 entry into human cells, usually by inhibiting nanomolar affinity interactions between the receptor-binding domain (RBD) of the viral spike (S-protein) and the angiotensin-converting enzyme 2 (ACE2) receptor.14,15 Recent reports indicate, but do not prove, that CPs containing high NAb titers can be beneficial when administered within a few days of hospitalization.9, 10, 11 Given later or in lower amounts, CP NAbs may be SS-208 unable to meaningfully supplement endogenous NAbs produced during seroconversion. Here, we report the successful administration of CP to a COVID-19 patient who was unable to generate her own antiviral antibodies (Abs) due to underlying B cell chronic lymphocytic leukemia (CLL). The CP contained high-titer NAbs (ID50 >5,000) and was given on day 33 after symptom onset. Her prolonged clinical Mouse monoclonal to CD152(PE) illness and fever resolved rapidly and she was discharged 4?days later, providing compelling evidence for a curative antiviral SS-208 effect of the administered NAbs, even though they were given late in the disease course. To place this case in context, we quantified NAb titers in additional banked and remnant CP units used to treat COVID-19 patients at the University of Alabama at Birmingham (UAB), as well as in CP recipients before and after transfusion. Many CP units from convalescent donors had only low-titer NAbs and thus were unable to usefully supplement endogenously produced Abs post-seroconversion. Results Presentation of the case and clinical course A 72-year-old female with a 20-year history of CLL developed a dry cough following exposure to her daughter (relative 1) who had contracted COVID-19 (Figure?1). The patient had a history of humoral immunodeficiency with chronic sinopulmonary infections requiring monthly intravenous immunoglobulin (IVIg) infusions for over 4 years. Given the progression of her CLL with Rai stage III disease in December 2019, obinutuzumab anti-CD20 B cell depletion immunotherapy was initiated. Her last treatment was 23?days before symptom onset and she had received IVIg 9?days earlier. Relative 1 developed a dry SS-208 cough 17?days after a holiday in Key West, FL (Figure?S1A), presented to a local hospital with headache, ageusia, and diarrhea, tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) analysis of a respiratory swab 11?days post-symptom onset (DPO), and was admitted with fever, dyspnea, and psychataxia. Her spouse (relative 2), who had also traveled, developed myalgia and headache, and was SARS-CoV-2 virus positive on DPO 8 (Figure?S1B). With worsening cough.