Chaolin Huang’s research while affiliated with China Academy of Chinese Medical Sciences and other places

After the coronavirus disease 2019 (COVID‐19) pandemic, the postacute effects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have gradually attracted attention. To precisely evaluate the health status of convalescent patients with COVID‐19, we analyzed symptom and proteome data of 442 plasma samples from healthy controls, hospitalized patients, and convalescent patients 6 or 12 months after SARS‐CoV‐2 infection. Symptoms analysis revealed distinct relationships in convalescent patients. Results of plasma protein expression levels showed that C1QA, C1QB, C2, CFH, CFHR1, and F10, which regulate the complement system and coagulation, remained highly expressed even at the 12‐month follow‐up compared with their levels in healthy individuals. By combining symptom and proteome data, 442 plasma samples were categorized into three subtypes: S1 (metabolism‐healthy), S2 (COVID‐19 retention), and S3 (long COVID). We speculated that convalescent patients reporting hair loss could have a better health status than those experiencing headaches and dyspnea. Compared to other convalescent patients, those reporting sleep disorders, appetite decrease, and muscle weakness may need more attention because they were classified into the S2 subtype, which had the most samples from hospitalized patients with COVID‐19. Subtyping convalescent patients with COVID‐19 may enable personalized treatments tailored to individual needs. This study provides valuable plasma proteomic datasets for further studies associated with long COVID.

The high costs associated with biological agents often limit accessibility for many patients, whereas biosimilars allow the wider application of biological treatment. The objectives of this phase I clinical trial were to compare the pharmacokinetics, immunogenicity, and safety profiles of the biosimilar adalimumab-WIBP and the reference product Humira® and to assess the precision of the bioequivalence evaluation. In this randomized, double-blind, parallel-group bioequivalence study, 164 healthy male Chinese participants were selected and randomly divided into two groups on a 1:1 ratio. The subjects were administered a single 40 mg subcutaneous dose of either adalimumab-WIBP or Humira®. Blood samples extracted at multiple intervals after administration were analyzed to interpret pharmacokinetic parameters, and any adverse events were documented. Alongside ensuring safety measures, the subjects were monitored for immunogenicity. The pharmacokinetic results demonstrated similar serum concentration–time curves in both groups. There were no significant differences in safety and no differences in immunogenicity profiles between the two groups. The bioequivalence was confirmed: the 90% confidence interval for the geometric mean ratio of the main pharmacokinetic parameters was within the range of 80–125%. The trial indicated the bioequivalence between adalimumab-WIBP and the reference product Humira® based on pharmacokinetics, immunogenicity, and safety profile. These findings reinforce the use of the adalimumab-WIBP biosimilar as a possible therapeutic alternative to Humira®.

Various substances in the blood plasma serve as prognostic indicators of the progression of COVID-19. Consequently, multi-omics studies, such as proteomic and metabolomics, are ongoing to identify accurate biomarkers. Cytokines and chemokines, which are crucial components of immune and inflammatory responses, play pivotal roles in the transition from mild to severe illness. To determine the relationship between plasma cytokines and the progression of COVID-19, we used four study cohorts to perform a systematic study of cytokine levels in patients with different disease stages. We observed differential cytokine expression between patients with persistent-mild disease and patients with mild-to-severe transformation. For instance, IL-4 and IL-17 levels significantly increased in patients with mild-to-severe transformation, indicating differences within the mild disease group. Subsequently, we analysed the changes in cytokine and chemokine expression in the plasma of patients undergoing two opposing processes: the transition from mild to severe illness and the transition from severe to mild illness. We identified several factors, such as reduced expression of IL-16 and IL-18 during the severe phase of the disease and up-regulated expression of IL-10, IP-10, and SCGF-β during the same period, indicative of the deterioration or improvement of patients’ conditions. These factors obtained from fine-tuned research cohorts could provide auxiliary indications for changes in the condition of COVID-19 patients.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.