PRE AND POST-MONOCLONAL INFUSION NEUTRALIZING ACTIVITY IN A SUBGROUP OF PATIENTS TREATED IN THE PRESENCE OF TWO SARS-COV-2 DOMINANT VARIANT OF CONCERN (VOCS) AND AN ONGOING VACCINATION. OVERALL CLINICAL EFFICACY OF TWO MONOCLONAL ANTIBODIES ASSOCIATION IN UMBRIA

Main Article Content

Elisabetta Schiaroli
Giuseppe Vittorio De Socio
Anna Gidari
Lisa Malincarne
Sara Benedetti
Alessandra Lanzi
Sabrina Bastianelli
Sara Pierucci
Chiara busti
Daniela Francisci

Keywords

COVID19, mAbs, VOCs, neutralizing activity

Abstract

Background and Objective: In patients with mild-to-moderate COVID-19 and at high risk of progression, casirivimab/imdevimab and bamlanivimab/etesivimab were utilized in Umbria from late April to November 2021. This period was characterized by an initial prevalence of alpha (B1.1.1.7) and its progressive substitution with the delta variant (B1.617.2). Many delta infections occurred in patients already recently vaccinated.


Our study aimed to observe the clinical outcome of patients treated with mAbs associations in a subgroup in which viral isolation was obtained, the pre and post-infusion neutralizing antibody activity against their viral isolate.


Methods: In this retrospective observational study, the clinical outcome before and 30 days after infusion, the baseline neutralizing activity of sera against their viral isolate, and the titers of neutralizing antibodies (NAbTs) one-hour post-infusion relative to the type of mAbs associations were evaluated.


Results: Better efficacy of the mAbs combinations relative to monotherapy regarding global hospitalization (p = 0.021) and 30 days symptoms (p<0.001) were seen. Infections after vaccination mostly occurred in the absence of neutralizing antibody titers (NAbT). SARS-CoV-2 delta variants were isolated within 2-4 months from vaccinations without NAbTs, or in the presence of high specific neutralizing activity after 5-6 months. NAbTs were higher after casirivimab/imdevimab infusion (p=0.001).


Conclusions: Alpha infections occurred prevalently in unvaccinated patients or after 5-6 months, while delta infections prevailed in vaccinated ones. A poor neutralizing activity in most of these patients was seen. A higher NAbT after infusion of casirivimab/imdevimab was observed.


 

Downloads

Download data is not yet available.
Abstract 1116 | PDF Downloads 224 HTML Downloads 90

References

1. Eugenia Quiros-Roldan , Silvia Amadasi , Isabella Zanella , Melania Degli Antoni , Samuele Storti , Giorgio Tiecco , Francesco Castelli . Monoclonal Antibodies against SARS-CoV-2: Current Scenario and Future Perspectives. Pharmaceuticals (Basel) 2021 Dec 6;14(12):1272. doi: 10.3390/ph14121272.
2. Food and Drug Administration. Letter to Eli Lilly and Company. 10 Nov 2020. https://www.fda.gov/media/143602/download
3. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19 November 21, 2020
4. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19. February 09, 2021
5. Peter Chen, Ajay Nirula , Barry Heller , Robert L Gottlieb, Joseph Boscia , Jason Morris , Gregory Huhn , Jose Cardona , Bharat Mocherla , Valentina Stosor , Imad Shawa , Andrew C Adams , Jacob Van Naarden , Kenneth L Custer , Lei Shen , Michael Durante, Gerard Oakley, Andrew E Schade , Janelle Sabo , Dipak R Patel , Paul Klekotka , Daniel M Skovronsky , BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med 2021 Jan 21; 384(3): 229-237.doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28.
6. Gottlieb RL, Nirula A, Chen P, Boscia J, Heller B, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Klekotka P, Shen L, Skovronsky DM. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.JAMA. 2021 Feb 16;325(7):632-644. doi: 10.1001/jama.2021.0202. PMID: 33475701
7. Tracking SARS-CoV-2 Variants. Available online: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants (accessed on 15 November 2021
8. Food and Drug Administration.April 16, 2021 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab.
9. Marco Falcone, Giusy Tiseo, Beatrice Valoriani, Chiara Barbieri, Sara Occhineri, Paola Mazzetti, Maria Linda Vatteroni, Lorenzo Roberto Suardi, Niccolo` Riccardi, Mauro Pistello, Danilo Tacconi, Francesco Menichetti. Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern. Infect Dis Ther. 2021 Dec;10(4):2479-2488. doi: 10.1007/s40121-021-00525-4. Epub 2021 Aug 25.PMID: 34435337
10. Schiaroli E, De Socio GV, Martinelli L, Malincarne L, Savoia M, Spinelli AL, Francisci D. Early Treatment with Bamlanivimab Alone does not Prevent COVID 19 Hospitalization and Its Post-Acute Sequelae. A Real Experience in Umbria, Italy. Mediterr J Hematol Infect Dis. 2021 Nov 1;13(1): e2021061. doi: 10.4084/MJHID.2021.061. eCollection 2021
11. Gidari A, Sabbatini S, Bastianelli S, Pierucci S, Busti C, Bartolini D, et al. SARS-CoV-2 Survival on Surfaces and the Effect of UV-C Light. Viruses 2021;13:408. doi: 10.3390/v13030408
12. Gidari A, Sabbatini S, Bastianelli S, Pierucci S, Busti C, Monari C, Luciani Pasqua B, Dragoni F, Schiaroli E, Zazzi M, Francisci D. Cross-neutralization of SARS CoV2 B.1.1.7 and P.1 variants in vaccinated, convalescent and P.1 infected. J Infect. 2021 Oct;83(4):467-472. doi: 10.1016/j.jinf.2021.07.019. Epub 2021 Jul 25 PMID: 34320390
13. Planas D, Veyer D, Baidaliuk A, Staropoli I, GuivelBenhassine F, Rajah MM, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596:276–8
14. Press Release N°37/2021 COVID-19: in Italy with over 90% of cases, the 'Delta variant' has replaced the 'Alpha' variant, ISS, July 30th 2021, Edited 10/01/2022
15. FDA STATEMENT Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant, Patrizia Cavazzoni, M.D, January 24, 2022
16. Stephen J Halpin , Claire McIvor , Gemma Whyatt ,Anastasia Adams , Olivia Harvey , Lyndsay McLean , Christopher Walshaw , Steven Kemp , Joanna Corrado , Rajinder Singh , Tamsin Collins , Rory J O'Connor , Manoj Sivan. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2021 Feb;93(2):1013-1022. doi: 10.1002/jmv.26368. Epub 2020 Aug 17.
17. Claudia Carvalho-Schneide, Emeline Laurent, Adrien Lemaignen, Emilie Beaufils , Céline Bourbao-Tournois , Saïd Laribi, Thomas Flament, Nicole Ferreira-Maldent, Franck ,Bruyère , Karl Stefic, Catherine Gaudy-Graffin, Leslie Grammatico-Guillon , Louis Bernard. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021 Feb;27(2):258-263. doi: 10.1016/j.cmi.2020.09.052.Epub 2020 Oct 5.

Most read articles by the same author(s)