Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS‐CoV‐2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS‐CoV‐2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100‐fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub‐nanomolar IC50, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)‐MoonTag provides protection against SARS‐CoV‐2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS‐CoV‐2 infections.
Here, we presented 11 cases with colistin-resistant Pseudomonas aeruginosa infection and co-existence of OXA-48 and NDM-1 in the ST235 high-risk clone. The molecular analyses were performed by Sanger sequencing and RT-PCR. The eight patients (72.7%) had an invasive infection and three (27.3%) had colonization. The 30-day mortality rate was 87.5% (7/8). Three patients (37.5%, 3/8) received colistin therapy before isolation of P. aeruginosa. In the Multilocus sequence typing (MLST) analysis of 11 isolates, eight (72.7%) isolates belonged to P. aeruginosa ST235 clone. All isolates were NDM-1 positive, and nine isolates (81.8%) were found to be positive for both OXA-48 and NDM-1. Sequences of pmrAB and phoPQ revealed numerous insertions and deletions in all isolates. In 10 isolates pmrAB and phoPQ were found to be upregulated. In conclusion, the co-existence of OXA-48 and NDM-1 genes in colistin-resistant P. aeruginosa ST235 high-risk clone indicates the spread of carbapenemases in clinical isolates and highlights need of continuous surveillance for high-risk clones of P. aeruginosa.
Objective: We aimed to describe the infectivity of adult and pediatric COVID-19 patients in the presence of viral shedding and anti-SARS-CoV-2 antibody response.
Materials and Methods:A total of 408 consequent samples from eleven adults and five pediatric patients with SARS-CoV-2 infection were included. Reverse transcription-polymerase chain reaction (RT-PCR) and viral culture were performed for the samples obtained every other day from saliva, nasopharynx, feces, serum, urine, and tear. Anti-SARS-CoV-2 antibodies were measured.
Results:The median duration of RNA shedding in all specimens was 7 (2-15) days in adults and 5 (3-19) days in children. The median duration from symptom onset to admission was three days. The viral RNA was positive in 44.7 % of the nasopharynx and 37.6% of saliva samples up to 16 days in adults and 19 days in children. We detected the latest viral culture positivity in the nasopharynx on day eight of symptoms. The viral RNA was found in 6.1% of feces, 4.4% of serum, 4.3 % of tear, 2.9% of urine. The earliest seroconversion was the seventh day for adults and the eighth day for children. On the 14th day, total antibody positivity was 78% in adults and 80% in children. After seroconversion, the viral RNA was still detected in the nasopharynx and saliva of three patients; however, the infectious virus was not present.
Conclusion:The infectivity of a positive patient is low after eight days of symptoms. The risk of fecal-oral transmission is very low, and strict hand hygiene measures could be preventive.
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