RESUMEN
Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 g/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP can be considered an integral instrument for COVID-19 prevention.
RESUMEN
PurposeWhen severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. MethodsWe studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1[->]3)-{beta}-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. ResultsOf the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA ([≥] 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. ConclusionsBacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease