English, South African, Brazilian, Indian. Or rather alpha, beta, gamma, delta, as the World Health Organization wanted to rename the variants of Sars-CoV-2 to detach them from the place where they were first sequenced and thus avoid geographical associations that could be misleading. Whatever you want to call them, it is clear that the variants, the delta in the lead, are the main concern of those who have to face the spread of the virus. Faced with their spread, one wonders about the effectiveness of the tools we have at our disposal: the vaccine shield seems to withstand the wave of variants, but what do we know about monoclonal antibodies? The first real life study that compared these drugs in the treatment of Covid infection caused by variants was conducted in Pisa and presented at the ECCMID congress a few weeks ago. “The results we have obtained show that unfortunately the variants modify the target of action of monoclonal antibodies and potentially can decrease their effectiveness. But this decrease is not the same for all molecules ”, explains Marco Falcone, associate in Infectious Diseases at the University of Pisa, infectious disease specialist at the Infectious Diseases Unit of the Pisan University Hospital directed by Francesco Menichetti and author of the study.
In Italy, three monoclonal antibodies have been authorized – the combinations bamlanivamb / etesevimab and casirivimab / imdevimab and sotrovimab – and in Pisa a specialized clinic was born immediately to manage this which, to date, is the only home therapy that has proven to be effective. . “In reality, the patient must be taken to the hospital for the infusion and for subsequent observation but then he can go home,” explains Falcone. “A management that is all in all easy that allows to intervene in fragile patients to prevent the disease from developing in a severe form”. The Pisan researchers therefore began to first administer the two approved combinations to patients as they presented themselves, first intercepting the beta variant, which had an outbreak in Umbria and then slowly spread to Tuscany, and then the others. “In our laboratory we always sequenced all the isolated viruses and then we could see in real time which drug worked best on which variant,” says Falcone. The study presented at the international congress, which will soon be published in “Infectious Diseases and Therapy”, tells precisely this and shows how bamlanivamb / etesevimab loses efficacy on the beta and gamma variants, which instead is maintained by casirivimab / imdevimab.
On the other hand, the AIFA also draws attention to the fact that the monoclonal antibodies anti-Sars-CoV-2 currently available, while presenting overlapping indications for use, differ from each other, on the basis of recent literature evidence, for ability to neutralize the different circulating variants. “All anti-Sars-CoV-2 antibodies available in Italy maintain adequate antiviral activity against the alpha variants, while the clinical efficacy and neutralizing activity of the bamlanivamb / etesevimab combination, unlike the other monoclonal antibodies available, appears to be reduced in case of infection with beta and gamma variants. Therefore, in the geographical areas where there is a circulation of beta and gamma variants, it is suggested to use monoclonal antibodies effective against all variants or to precede the start of therapy by genotyping / sequencing “, reads the note of 5 August. . “However, it is not always possible to do the sequencing before starting the therapy, even for a matter of time. So the decision on which drug to use must be made on the basis of epidemiology and the scientific knowledge we have accumulated ”, concludes Falcone. And speaking of new evidence, based on the results of the Recovery study, which demonstrated the efficacy in terms of decreased mortality of treatment with casirivimab and imdevimab in hospitalized adult patients, even on conventional oxygen therapy and with negative serology for IgG antibodies anti-Spike of SARS-CoV-2, Aifa has decided to extend the possible use of the combination in this subpopulation.
.