Effectiveness and Tolerability of Early Treatment with Monoclonal Antibodies against SARS-Cov-2: Results from A Real-Life Study before Omicron Surge (preprint)

Abstract Despite the lightning-fast advances in the management of SARS-CoV after 2 years of pandemic, COVID-19 continues to pose a challenge for fragile patients, who could benefit from early administration of monoclonal antibodies (mAbs) to reduce the risk of severe disease progression. We conducted a prospective study to evaluate effectiveness of mAbs against SARS-CoV-2 among patients at risk for severe disease progression, namely elderly and those with comorbidities, before the omicron variant surge. Patients were treated with either casirivimab/imdevimab, sotrovimab, and bamlanivimab/etesevimab. The rates and risk factos for clinical worsening, hospitalization, ICU admission and death (unfavourable outcomes) were evaluated. A stratified analysis according to the presence of SARS-CoV-2 IgG was also performed. Among 185 included patients, we showed low rates of unfavorable outcomes (9.2%), which were more frequent in patients with chronic kidney disease (aOR: 10.44, 95CI: 1.73-63.03; p<0.05) and basal D-dimer serum concentrations >600 ng/ml (aOR 21.74, 95CI: 1.18-397.70; p<0.05). Patients with negative SARS-CoV-2 serology at baseline showed higher C-reactive protein values compared with patients with positive serology (p <0.05) and showed a trend toward a higher admission rate to SICU and ICU compared with patients with positive serology. Our results thus showed, in a real-life setting, the efficacy of mAbs against SARS-CoV-2 before Omicron surge when the available mabs become not effective.

Serological Response and Clinical Protection of Anti-SARS-CoV-2 Vaccination and the Role of Immunosuppressive Drugs in a Cohort of Kidney Transplant Patients.

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines.

Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study (preprint)

Molnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy. We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, p<0.01). Globally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions. In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.

Monoclonal antibodies against SARS-CoV-2: potential game-changer still underused (preprint)

Even several months after the start of a massive vaccination campaign against COVID-19, mortality and hospital admission are still in considerable numbers in many nations. Monoclonal antibodies are the ideal complement to vaccination in high-risk subjects who have been infected by SARS-CoV-2 and are at high risk of developing severe disease. Combining data provided by clinal trials and demographics of SARS-CoV-2 infections, this analysis tries to predict the benefits of an extensive use of monoclonal antibodies to reduce hospital admissions, deaths, and costs.