{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:29:15Z","timestamp":1785569355662,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients\u2019 median age was 66 years (IQR 50\u201374 years) and approximately half of them (47.6%, 10\/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3\/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.<\/jats:p>","DOI":"10.3390\/v14071443","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T01:40:36Z","timestamp":1656639636000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-0580","authenticated-orcid":false,"given":"Massimo","family":"Franchini","sequence":"first","affiliation":[{"name":"Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-195X","authenticated-orcid":false,"given":"Daniele","family":"Focosi","sequence":"additional","affiliation":[{"name":"North-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Percivalle","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Beccaria","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Garuti","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Arar","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Pecoriello","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Spreafico","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Greco","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bertacco","sequence":"additional","affiliation":[{"name":"Intensive Care Respiratory Unit, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ghirardini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-7795","authenticated-orcid":false,"given":"Michele","family":"Schiavulli","sequence":"additional","affiliation":[{"name":"Regional Reference Center for Coagulation Disorders, Santobono-Pausilipon Children\u2019s Hospital, AORN, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzzica","family":"Stefania","sequence":"additional","affiliation":[{"name":"Pediatric Emergency and Short Stay Unit, Santobono-Pausilipon Children\u2019s Hospital, AORN, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaililja","family":"Gagliardo","sequence":"additional","affiliation":[{"name":"Pediatric Emergency and Short Stay Unit, Santobono-Pausilipon Children\u2019s Hospital, AORN, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e8 Camilla","family":"Sammartino","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Zani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Ballotari","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Glingani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, 46100 Mantua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1001\/jama.2020.4783","article-title":"Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma","volume":"323","author":"Shen","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.3324\/haematol.2020.261784","article-title":"Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial","volume":"105","author":"Perotti","year":"2020","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1186\/s12879-021-06829-7","article-title":"Association between convalescent plasma treatment and mortality in COVID-19: A collaborative systematic review and meta-analysis of randomized clinical trials","volume":"21","author":"Axfors","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref_4","unstructured":"(2022, April 01). WHO Recommends Against the Use of Convalescent Plasma to Treat COVID-19. Available online: https:\/\/www.who.int\/news\/item\/07-12-2021-who-recommends-against-the-use-of-convalescent-plasma-to-treat-covid-19#:~:text=Convalescent%20plasma%20is%20a%20transfusion,while%20it%20has%20significant%20costs."},{"key":"ref_5","unstructured":"(2022, April 01). IDSA Guideline on the Management and Treatment of COVID-19. Available online: https:\/\/www.idsociety.org\/globalassets\/idsa\/practice-guidelines\/covid-19\/treatment\/idsa-covid-19-gl-tx-and-mgmt---convalescent-plasma-2022-02-03.pdf."},{"key":"ref_6","first-page":"277","article-title":"Italian Society for Transfusion Medicine and Immunohaematology (SIMTI), and the Italian Society for Haemapheresis and Cell Manipulation (SIdEM). Position paper on the use of COVID-19 convalescent plasma: An update","volume":"19","author":"Prati","year":"2021","journal-title":"Blood Transfus."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.mayocp.2021.06.011","article-title":"How Safe Is COVID-19 Convalescent Plasma?","volume":"96","author":"Franchini","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1003872","DOI":"10.1371\/journal.pmed.1003872","article-title":"Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study","volume":"18","author":"Senefeld","year":"2021","journal-title":"PLoS Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0020021","DOI":"10.1128\/cmr.00200-21","article-title":"COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes","volume":"9","author":"Focosi","year":"2022","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","unstructured":"(2022, April 01). FDA, Available online: https:\/\/www.fda.gov\/media\/141477\/download."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Franchini, M., Glingani, C., De Donno, G., Lucchini, G., Beccaria, M., Amato, M., Castelli, G.P., Bianciardi, L., Pagani, M., and Ghirardini, M. (2022). Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience. Life, 12.","DOI":"10.3390\/life12030420"},{"key":"ref_12","first-page":"42","article-title":"Outcome of SARS CoV-2 inpatients treated with convalescent plasma: One-year of data from the Veneto region (Italy) Registry","volume":"97","author":"Marson","year":"2021","journal-title":"Eur. J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1080\/10428194.2021.1872070","article-title":"Convalescent hyperimmune plasma for chemo-immunotherapy induced immunodeficiency in COVID-19 patients with hematological malignancies","volume":"62","author":"Ferrari","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2136246","DOI":"10.1001\/jamanetworkopen.2021.36246","article-title":"Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial","volume":"4","author":"Menichetti","year":"2021","journal-title":"JAMA Netw. Open."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejim.2022.01.016","article-title":"Convalescent plasma for COVID-19. TSUNAMI is not the final word","volume":"97","author":"Franchini","year":"2022","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","unstructured":"Italian Ministry of Health (2022, April 01). COVID-19 in Italy, Available online: https:\/\/www.salute.gov.it\/portale\/nuovocoronavirus\/dettaglioContenutiNuovoCoronavirus.jsp?lingua=english&id=5367&area=nuovoCoronavirus&menu=vuoto."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.mayocpiqo.2021.01.010","article-title":"Safety and Efficacy of Convalescent Plasma in Elderly COVID-19 Patients: The RESCUE Trial","volume":"5","author":"Franchini","year":"2021","journal-title":"Mayo Clin. Proc. Innov. Qual. Outcomes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.tracli.2021.02.005","article-title":"Impact of pathogen-reduction technologies on COVID-19 convalescent plasma potency","volume":"28","author":"Focosi","year":"2021","journal-title":"Transfus. Clin. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/vox.12940","article-title":"Operational protocol for donation of anti-COVID-19 convalescent plasma in Italy","volume":"116","author":"Franchini","year":"2020","journal-title":"Vox Sang."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102817","DOI":"10.1016\/j.transci.2020.102817","article-title":"Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19","volume":"59","author":"Accorsi","year":"2020","journal-title":"Transfus. Apher. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"198786","DOI":"10.1016\/j.virusres.2022.198786","article-title":"Comparative analysis of SARS-CoV-2 quasispecies in the upper and lower respiratory tract shows an ongoing evolution in the spike cleavage site","volume":"315","author":"Gaiarsa","year":"2022","journal-title":"Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sammartino, J.C., Cassaniti, I., Ferrari, A., Giardina, F., Ferrari, G., Zavaglio, F., Paolucci, S., Lilleri, D., Piralla, A., and Baldanti, F. (2022). Evaluation of the Neutralizing Antibodies Response against 14 SARS-CoV-2 Variants in BNT162b2 Vaccinated Na\u00efve and COVID-19 Positive Healthcare Workers from a Northern Italian Hospital. Vaccines, 10.","DOI":"10.3390\/vaccines10050703"},{"key":"ref_23","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2001031","DOI":"10.2807\/1560-7917.ES.2020.25.24.2001031","article-title":"Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi red Zone in Lombardy, Italy, as at 06 April 2020","volume":"25","author":"Percivalle","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/trf.16887","article-title":"Neutralizing antibody levels against SARS-CoV-2 variants of concern Delta and Omicron in vaccine breakthrough-infected blood donors","volume":"62","author":"Franchini","year":"2022","journal-title":"Transfusion"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.mayocp.2021.11.001","article-title":"Vax-Plasma in Patients With Refractory COVID-19","volume":"97","author":"Ordaya","year":"2022","journal-title":"Mayo Clin. Proc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41467-020-20688-x","article-title":"Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy","volume":"12","author":"Alteri","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_28","first-page":"559","article-title":"The COVID-19 Epidemic: The experience in the Social and Health Care Center of the Mantua District (Lombardy Region, Northern Italy)","volume":"45","author":"Casari","year":"2021","journal-title":"Epidemiol. Prev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Destras, G., Bal, A., Simon, B., Lina, B., and Josset, L. (2022). Sotrovimab drives SARS-CoV-2 Omicron variant evolution in immunocompromised patients. Lancet Microbe.","DOI":"10.1101\/2022.04.08.22273513"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:01Z","timestamp":1760139661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["v14071443"],"URL":"https:\/\/doi.org\/10.3390\/v14071443","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}