Discussion
nausea, SARS-CoV-2 infection, pain, AG86, infection
VIRUS, SARS-COV-2 INFECTION, ALLERGIC REACTION, ADVERSE EFFECTS, INFECTION
The nasal spray antibody cocktail A8G6 had demonstrated broad spectrum potency blocking the SARS-CoV-2 infection in our previous preclinical data and also demonstrated favorable safety profile in a first-in-human trial (unpublished data, manuscript in preparation). In this study, we conducted an open-label, non-randomized, two-arm, blank-controlled trial among close contacts of COVID-19 patients in several designated quarantine hotels, during the COVID-19 outbreak occurred in November, 2022 in Chongqing, China. The intranasal spray antibody cocktail A8G6 was assessed to the effectiveness and safety for the post-exposure prophylaxis of COVID-19 in the real-world. Our data suggest that the application of A8G6 in the close contacts within the 72 h exposure decreased COVID-19 incidence rate by more than 30%. Moreover, the A8G6 treatment delayed the occurrence of SARS-CoV-2 infection by at least one day.At present, most previously authorized COVID-19 antibody treatments under EUA were administrated via vein or intramuscular injection with a high dosage. Those treatment also had several adverse effects that affect quality of life, including pain at the site of injection, allergic reaction, nausea and so onCurrent data in this study showed that 6.9% of A8G6 treated participant became SARS-CoV-2 positive (vs 44.4% in the blank control group) during the study period. Our results suggested that post-infection A8G6 treatment provided limited benefits on viral load reduction and time to viral clearance. This is consistent with the potential mechanism of action of A8G6 nasal spray. Once SARS-CoV-2 virus enters into the cells and starts viral replication, A8G6 neutralizing antibody has limited efficacy to stop the viral replication. Our data also indicated that the efficiency of viral replication of these two groups were similarThere were several limitations for this study. First limitation is the lack of a placebo arm. We did not conduct this study with the double-blind procedure because there was a small window of time to initiate and complete the study so not allowing enough time for the placebo to be produced before the trial. Second limitation is the lack of participant randomization in the study design. This was primarily due to a large percentage of eligible participants, especially older people, showed their unwillingness or worries to take the A8G6 treatment at the time of enrollment. Therefore, we had to assign those participants to blank-controlled group. Under this situation, complete randomization was impossible. However, we supposed that our data and conclusion were not affected by ages of these participants. Because in our previous first-in-human trial, pharmacokinetics of A8G6 nasal spray showed that A8G6 has minimum penetration in the systemic blood circulation. Neutralizing activity of A8G6 against SARS-CoV-2 focuses on nasal mucosa, which is less affected by age. Third limitation is the lack of participants developing severe COVID-19 that need hospitalization due to small sample size. Therefore, this study did not assess the efficacy of A8G6 in preventing severe COVID-19. During the study period, there was an adjustment of the public health policy of the COVID-19 pandemic in China, that the SARS-CoV-2 infected persons no longer were reported in the future. As a result, the definition of close contacts became difficult and it became difficult to enroll more participants to increase the sample size. Fourth limitation is that the study was conducted in the designated quarantine hotels. Study participants were assumed to be single-exposure to positive COVID-19 individuals. The effects of increased infection risks of multiple exposures in the real world on the A8G6 efficacy should be considered in the further study.In conclusion, we observed potent post-exposure prevention efficacy of intranasal spray AG86 antibody combination in close contacts of COVID-19 patients. This proof-of-concept study result suggested the potential beneficial effect of neutralizing antibody administrated as nasal spray in COVID-19 prevention. Currently A8G6 nasal spray is under clinical development to further assess its efficacy and safety.