Prevalence of inappropriate use of nirmatrelvir-ritonavir antiviral therapy in hospitalized patients: A multi-centre retrospective study in China.

BACKGROUND: Nirmatrelvir-ritonavir (NMVr) is a recently developed antiviral agent for treating coronavirus disease 2019 (COVID-19); however, data describing its appropriate use are scarce. This study examined the prevalence of inappropriate use of NMVr in a Chinese hospital setting. METHODS: A multi-centre retrospective chart review was performed for all hospitalized patients who received NMVr between 15 December 2022 and 15 February 2023 in four university-affiliated hospitals in Hangzhou, China. A multi-disciplinary team of experts developed the evaluation criteria. A group of senior clinical pharmacists examined and verified the suitability of NMVr prescriptions. RESULTS: In total, 247 patients received NMVr during the study period, of which 13.4% (n=31) met all the criteria for appropriate use of NMVr. The main types of inappropriate use of NMVr were delayed initiation of treatment (n=147, 59.5%), no dose adjustment for moderate renal impairment (n=46, 18.6%), use in patients with severe-to-critical COVID-19 (n=49, 19.8%), presence of contra-indicated drug‒drug interactions with other medications (n=36, 14.6%), and prescription for patients without a confirmed diagnosis of COVID-19 (n=36, 14.6%). CONCLUSIONS: The proportion of inappropriate use of NMVr was particularly high in the Chinese hospital setting, highlighting the urgent need to improve the appropriate use of NMVr.

Multisystem inflammatory syndrome (MIS-C) with SARS-CoV-2 omicron variant BA.2.38 in a four-year-old Chinese girl: A case report.

We report a severe COVID-19 complicated with MIS-C in a girl treated by the author in China, and discuss the current research status and progress in the diagnosis and therapy of MIS-C in children. The patient was a 4-year-old child previously healthy who was referred to the hospital with a complaint of fever, finally, Multisystem inflammatory syndrome was diagnosed with COVID-19.

Procalcitonin in infectious diseases: a bibliometric analysis.

BACKGROUND: Infectious disease is ubiquitous and can represent a major threat to human health. Procalcitonin (PCT) is mainly used to identify the severity of bacterial infections, which can be secondary to many non-bacterial infectious diseases. The purpose of this study was to evaluate current research in the field of infectious diseases and to suggest directions for further investigation. METHODS: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection (WOSCC) was used as the search data source. The search parameters including the search scope were limited to "infectious disease" and the search term was "procalcitonin". The time range of the target literature was 1900 to the final search date of this research (May 7, 2021), and the language was limited to English. The full records of the search results and cited references were exported in plain text format, and Citespace software was used to analyze the documents. RESULTS: A total of 996 related research documents were found, and the number increased significantly in 2020. The United States, Germany, and the United Kingdom were the main sources of research, and the main research institutions were Aarhus University Hospital and Harvard University. The main journals are publishing material were Clin Infect Dis, Lancet, and Crit Care Med. Analysis of key words showed that the most common current research topics were sepsis and biomarkers of disease monitoring. CONCLUSIONS: Research on infectious disease and the role of PCT is increasing. The main research topics are sepsis and biomarkers for disease monitoring.

Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein-protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2.

Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. METHODS: PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. RESULTS: Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. CONCLUSION: We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.