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The true historical origin of convalescent plasma therapy

2020; Elsevier BV; Volume: 59; Issue: 5 Linguagem: Inglês

10.1016/j.transci.2020.102847

1878-1683

Piero Marson, Andrea Cozza, Giustina De Silvestro,

Historical Psychiatry and Medical Practices

The use of convalescent plasma, a strategy of passive immunization that has been applied in the prevention and treatment of epidemic infections for more than 100 years [1Garroud O. Heshmati F. Pozzetto B. Lefrere F. Girot R. Saillol A. et al.Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow.Transfus Clin Biol. 2016; 23: 39-44Crossref PubMed Scopus (106) Google Scholar], has been proposed and performed also during the recent COVID-19 pandemic [2Seghatchian J. Lanza F. Convalescent plasma, an apheresis research project targeting and motivating the fully recovered COVID 19 patients: a rousing message of clinical benefit to both donors and recipient alike.Transfus Apher Sci. 2020; https://doi.org/10.1016/transci.2020.102792Crossref Google Scholar]. Generally the convalescent plasma use during the Spanish influenza A (H1N1) pneumonia (pandemic of 1918–1920) has been reported as its first application [3Brown B.L. McCullough J. Treatment for emerging viruses: convalescent plasma and COVID-19.Transfus Apher Sci. 2020; https://doi.org/10.1016/transci.2020.102790Crossref PubMed Google Scholar, 4Cao H. Shi Y. Convalescent plasma: possible therapy for novel coronavirus disease 2019.Transfusion. 2020; 60: 1078-1083Crossref PubMed Scopus (25) Google Scholar, 5Tiberghien P. de Lamballiere X. Morel P. Gallian P. Lacombe K. Yazdanpanah Y. Collecting and evaluating convalescent plasma for COVID-19 tratment: why and how?.Vox Sang. 2020; https://doi.org/10.1111/vox.12926Crossref Scopus (120) Google Scholar, 6Rajendran K. Krishnasamy N. Rangarajan J. Rathinam J. Natarajan M. Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: systematic review.J Med Virol. 2020; https://doi.org/10.1002/jmv.25961Crossref PubMed Scopus (235) Google Scholar]. In fact, several studies conducted during this pandemic suggested that the convalescent plasma could be effective in reducing mortality risk, as later confirmed by the meta-analysis carried out by Luke et al. in 2006 [7Luke T.C. Kilbane E.M. Jackson J.L. Hoffman S.L. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H1N1 treatment?.Ann Intern Med. 2006; 145: 599-609Crossref PubMed Scopus (501) Google Scholar], involving overall 1,703 patients from 8 suitable reports. Actually, serotherapy from convalescent patients has been long used also before the Spanish influenza pandemic. For instance, it was tried as a medical treatment of acute paralysis in the 1916 New York outbreak of poliomyelitis [8Anonymous Monograph on the epidemic of poliomyelitis (infantile paralysis) in New York City in 1916. New York City Department of Health, New York, 1917 (cited by Wyatt HV. Before the vaccines: medical treatments of acute paralysis in the 1916 New York epidemic of poliomyelitis.Open Microbiol J. 2014; 8: 144-147PubMed Google Scholar]. Again in 1916, Nicolle and Conseil applied serotherapy to contain a small measles epidemic in Tunis [9Nicolle C. Conseil E. Pouvoir preventif du serum d'un malade convalescent de rougeole.Bull Soc Méd Hôp Paris. 1918; 42: 336-338Google Scholar]. In 1915 Hess used the same therapeutic option to treat mumps and prevent its testicular complications [10Hess A.F. A protective therapy for mumps.Am J Dis Child. 1915; 10: 99-103Google Scholar]. Finally, the Italian Francesco Cenci is credited to be the first to use convalescent serum as a therapeutic tool, to protect children exposed to measles infection [11Pontecorvo M. Storia delle vaccinazioni: dalle origini ai giorni nostri. Ciba Geigy Edizioni, Origgio1991: 104Google Scholar]. It was possible to get the original article by Cenci [12Cenci F. Alcune esperienze di sieroimmunizzazione e sieroterapia nel morbillo.Riv Clin Ped. 1907; 5: 1017-1025Google Scholar], published in 1907 in an Italian pediatric journal (Fig. 1). The author was a public health doctor working in a small town of Central Italy near Perugia (Campello sul Clitunno, about 1,800 inhabitants in the early twentieth century [13ISTAT data, cited in https://it.wikipedia.org/wiki/Campello_sul_Clitunno.Google Scholar]). Starting from the observation that, once cured of measles, it is very unlikely that a patient will fall ill a second time, and thus presuming the existence of some serum protective factor, during an epidemic outbreak in 1901 Cenci practiced a bloodletting of 600 mL to a 20-year old man, three weeks after recovery from measles. After blood coagulation, he collected serum in three sterilized tubes, adding a solution of phenic acid as a protective agent. The convalescent serum was then inoculated to four children aged between 4 and 8 years, who did not contract measles after this treatment, unlike their cohabitant siblings. It has to be noticed that, to ensure safety of the product, 60 h before administration to patients, a portion of serum was inoculated into the peritoneum of a rabbit and also into the arm of Cenci himself, without this causing general or local reactions. In these cases, however, human convalescent serum was successfully used as a prophylactic agent. This prophylactic application lasted several decades, as measles had a high mortality (6–7 %) in some populations [14Casadevall A. Scharff M.D. Return to the past: the case for antibody-based therapies in infectious diseases.Clin Infect Dis. 1995; 21: 150-161Crossref PubMed Scopus (264) Google Scholar]. In December 1906, there was another outbreak of measles in the Campello sul Clitunno area, with about forty sick children. Cenci successfully repeated prophylaxis through the convalescent serum inoculation. Moreover, in a child with a severe form of measles with pneumonia serotherapy made infection milder and duration of the disease shorter. This case unequivocally represents a therapeutic and not only prophylactic use of the convalescent serum, probably for the first time. As a matter of facts, Cenci reported that a similar treatment had been made on two children in 1900, in the Pediatric Clinic of Rome directed by Luigi Concetti [15Concetti L. L'insegnamento della pediatria in Roma. III Rendiconto statistico-clinico del biennio 1898–99 e 1899–1900. Tip. Centenari, Roma1901: 69Google Scholar], that was the first to use serotherapy against diphtheria in Italy, after the seminal studies by Emil Behring and Shibasaburo Kitasato [16Simon J. Emil Behring's medical culture: from disinfection to serotherapy.Med Hist. 2007; 51: 201-218Crossref PubMed Scopus (28) Google Scholar]. Evidently, this therapeutic innovation was soon put into practice in an Italian suburban area, suggesting already then a good public health system. In fact, it may seem singular that this pioneering investigation was fully performed outside academic or research centres, and moreover in a deeply rural area of Italy, but it is well known that intuition and experimentalism at that time were typical of the whole medical class, which still breathed the cultural ground of the nineteenth century, namely a truly innovative period in the history of medicine. Piero Marson: Writing - original draft, Conceptualization. Andrea Cozza: Investigation. Giustina De Silvestro: Supervision. We declare no relevant conflicts of interest.