Convalescent blood plasma (CBP) donated by recovered COVID-19 patients – A comment

Abstract

Convalescere: a latin word for ‘to recover’ with linguistics reaching into current English - says it all: the revival of patients from COVID-19 infection to a healthy (virus-free?) life. [[1]Lopez-Otin C. Kroemer G. Hallmarks of health.Cell. 2021; 184: 33-63Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar,[2]Conti A.A. Historical evolution of the cocept of health in Western medicine.Acta Biomed. 2018; 83: 352-354Google Scholar]. Even after a poorly defined waiting period of one month, blood banks collect blood plasma during the dynamics of recovery: donor recruitment impossible without med lab assessment of fitness (Table 1) [[3]Bloch E.M. Shoham S. Tobian A.A. coautors Deployment of convalescent plasma for the prevention and treatment of COVID-19.J Clin Invest. 2020; 130: 2757-2765Crossref PubMed Scopus (490) Google Scholar]. Whereas the safety of apheresis plasma donation was scrutinized during the development of this technique and persists to be acknowleged since inception, the safety procedures required for convalescent blood plasma (CBP) donation are questionable. [[4]Joyner M.J. Wright R.S. Casadevall A. Early safety indicators of COVID-19 convalescent plasma in 5,000 patients.J Clin Invest. 2020; 130 (coautors): 4791-4797Crossref PubMed Scopus (250) Google Scholar].Table 1Proposed med lab tests within reference intervals to estimate fitness for donation of convalescent plasma.clinical chemistryhematologyimmunologymicrobiologystandard: CRP, ferritin, creatinine, LDH, ALT, CK, bilirubinhb, RBC count, ABO histo-blood typeIg levels (polyclonal, IgG,IgM, IgA, SARS-CoV-2 Ig titers), C5a, SC5b-9regular blood donation tests (**HIV, HCV, HBV, syphiliss.)High titered SARS-CoV levels (hyperimmune); different commercially available assays.LDH lactate dehydrogenase.ALT alanine aminotransferase.CK creatine kinase.** HIV, HCV, HBV, syphiliss. Open table in a new tab High titered SARS-CoV levels (hyperimmune); different commercially available assays. LDH lactate dehydrogenase. ALT alanine aminotransferase. CK creatine kinase. The infant-Covid-19 group study [[5]Khanna N. Weisser M. Buser A. Efficacy of COVID-19 pathogen inactivated convalescent plasma for patients with moderate to severe acute COVD-19: a case matched control study.Blood. 2020; 136 (coautors): 29-30Crossref Google Scholar,[6]Libster R. Pérez Marc G.P. Group I-C Early high-titer plasma therapy to prevent severe Covid-19 in older adults.New Engl J Med. 2021; Crossref PubMed Scopus (501) Google Scholar] clearly showed that early administration of high-titer CBP can reduce progression of COVID-19. Ever since CBP was asserted with other infectious diseases than SARS-CoV 2, specific sets of lab assays were required to meet donation requirements; as of 2020, under the pressure of treating an ever increasing number of younger COVID 19 patients [7Huang L. Zhang X. Xu A. Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: a prospective contact-tracing study.J Infect Public Health. 2020; (coauthors)Google Scholar, 8Jafari R. Kouchaksrael S. Hosseini R. Nayeb M. Ranbajar A. Convalescent plasma:an old trick for the treatment of COVID-19.J Pedr Rev. 2020; 8: 209-210Crossref Google Scholar, 9Felsenstein S. Willis E. Lythgoe H. McCann L. Cleary A. Mahmood K. et al.Presentation, treatment response and short-term outcomes in paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS).J Clin Med. 2020; 14Google Scholar] we cannot remain inactive to apply simple procedures prior to CBP, this fresh-frozen semi- stable blood product remaining remote from pharmaceutical approaches as those seen for polyconal and/or monoclonal antibodies (abs) [[10]Weinreich D.M. Sivapalasingam S. Norton T. Investigators T REGN-COV2, a Neutralizing Antibody Cocktail.New Engl J Med. 2020; : 17Google Scholar]. Pathogen inactivation is has now been achieved applying such methods as Amotosalen UVA which blocks DNA and RNA replication - this Intercept Blood System is used for blood plasma, without compromising anti SARS-CoV-2 activity [[5]Khanna N. Weisser M. Buser A. Efficacy of COVID-19 pathogen inactivated convalescent plasma for patients with moderate to severe acute COVD-19: a case matched control study.Blood. 2020; 136 (coautors): 29-30Crossref Google Scholar]. Thus, the containment of anti-SARS-CoV 2 antibodies in CBP produced by the convalescing donor or added as spike, is more and more perceived as bringing therapeutic efficacy to some patients receiving CBP [[11]Lung T. Risch L. Risch M. Sakem B. Wurzner R. Nydegger U. The utility of complement assays in clinical immunology: a comprehensive review.J Autoimmun. 2018; 95: 191-200Crossref PubMed Scopus (3) Google Scholar,[12]Lung T. Kazatchkine M. Risch L. Risch M. Nydegger U. A consideration of convalescent plasma and plasmaderivatives in the care of severely- ill patients with COVID 19.Transfus Apher Sci. 2020; 59Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar]. In addition, glycan constitution of the abs seems to confer virotoxicity: afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity [[13]Larsen M.D. de Graaf E.L. Sonneveld MEea Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.Science. 2020; : eabc8378PubMed Google Scholar]. The polyclonal machinery in humans which synthesizes abs can best be screened using a pan-immunoglobulin assay quantifying specificities towards receptor-binding domain of the SARS-CoV-2 S1-subunit of the spike protein [[14]Schaffner A. Risch L. Risch M. Characterization of a pan-immunoglobulin assay quantifying antibodies directed against the receptor binding domain of the SARS-CoV-2 S1-subunit of the spike protein: a population-based study.J Clin Med. 2020; 9 (coauthors): 3989Crossref Scopus (26) Google Scholar] or assays based on PCR neutralization [[15]Danh K. Karp D.C. Tsai C. Detection of SARS-CoV-2 neutralizing antibodies with a cell-free PCR assay. medRxiv, 2020Crossref Scopus (0) Google Scholar]. We have recently proposed that CBP contains as yet to be defined components different from anti-SARS-CoV-2 abs; one may underline this assumption adressing the GIS (geographic information system) approach forwarded by Topol et al. [[16]Topol E. Individualized medicine from prewomb to tomb.Cell. 2014; 157: 241-253Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar]. This can be completed with data-driven Bayesian networks estimated to uncover complex interrelationships and confounding effects [[12]Lung T. Kazatchkine M. Risch L. Risch M. Nydegger U. A consideration of convalescent plasma and plasmaderivatives in the care of severely- ill patients with COVID 19.Transfus Apher Sci. 2020; 59Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar,[17]Cippa P.E. Cugnata F. Di Serio C. A data-driven approach to identify risk profiles and protective drugs in COVID-19.Proc Natl Acad Sci U S A. 2020; 118 (coauthors)Crossref PubMed Scopus (27) Google Scholar]. Recovery from COVID-19, including expiration of SARS-CoV-2 load, may in fact depend on metabolome and proteome including different components from abs alone and scoop from multiple and superimposed layers of innate and acquired immune events; recovery also takes hold of such components as α1−antitrypsin, C1 esterase inhibitor, metalloproteinase or shed IL- receptors: their putative convalescing potential might get lost to the convalescing/recovering COVID 19 patient. The involvement of the DNA ladder, here coding for ABO histo-blood groups and complement in COVID -19 just begins to be considered on a patients` chart [[18]Valenti L. Griffini S. Cugno M. Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19.J Autoimmun. 2021; (coautors)Crossref Scopus (33) Google Scholar,[19]Ellinghaus D. Degenhardt F. Karlsen T.H. The ABO blood group loccus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. medRxiv, 2020Google Scholar]. The medicalized smartphone [[20]Topol E. The patient will see you now. Basic Books, New York2015Google Scholar] software on a bracelet, programmed to clear a convalescent COVID-19 patient to qualify for plasma donation, may enable advance us to recruit sufficient CBP donors - should this treatment become part of good medical practice.