Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression

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1. Version published to 10.1038/s41392-022-00952-w

   Mar 18, 2022
2. 

   ScreenIT

   Oct 22, 2021

   SciScore for 10.1101/2021.10.19.21263786: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Consent: Patient enrollment and experiment animal: All COVID-19 patients enrolled in this study have received a written informed consent upon admission into the Shanghai Public Health Clinical Center (SPHCC), the designated hospital for COVID-19 patients in Shanghai, China10. IRB: This study was approved by the Ethics Committee of the SPHCC (YJ-2020-S123-02).
   Sex as a biological variable	Exclusion criteria for COVID-19 patients were listed as below: 1) Serious non-infectious pulmonary diseases, including pulmonary tumor, pulmonary edema, atelectasis, pulmonary embolism, pulmonary eosinophilic infiltration, pulmonary vasculitis etc.; 2) Severe liver and kidney dysfunction: a) ALT and AST value …

   SciScore for 10.1101/2021.10.19.21263786: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	Consent: Patient enrollment and experiment animal: All COVID-19 patients enrolled in this study have received a written informed consent upon admission into the Shanghai Public Health Clinical Center (SPHCC), the designated hospital for COVID-19 patients in Shanghai, China10. IRB: This study was approved by the Ethics Committee of the SPHCC (YJ-2020-S123-02).
   Sex as a biological variable	Exclusion criteria for COVID-19 patients were listed as below: 1) Serious non-infectious pulmonary diseases, including pulmonary tumor, pulmonary edema, atelectasis, pulmonary embolism, pulmonary eosinophilic infiltration, pulmonary vasculitis etc.; 2) Severe liver and kidney dysfunction: a) ALT and AST value were more than 10 times higher than the upper limit of normal value; b) serum creatinine value was more than 1.5 times higher than the upper limit of normal value; c) total bilirubin was more than 2 times the upper limit of normal value; 3) Patients with biliary obstruction; 4) Pregnant women (urine or serum pregnancy test positive) or lactating women; 5) Other factors considered unsuitable by the researchers for this trial, or the situation that may increase the risk of subjects or interfere with the clinical trial.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Cell Line Authentication	not detected.

   Table 2: Resources

   Experimental Models: Cell Lines
   Sentences	Resources
   Moreover, we evaluated whether hymecromone can reduce hyaluronan levels in the cell using HEK293T and HUVEC cells.	HEK293T suggested: CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)
   Twenty-four hours after HEK293T and HUVEC were treated with DMSO or hymecromone (250 μg/ml), cell culture mediums were collected to detect the hyaluronan levels using the Hyaluronan DuoSet ELISA (R&D Systems) according to the manufacturer’s descriptions.	HUVEC suggested: None
   Experimental Models: Organisms/Strains
   Sentences	Resources
   Adult C57BL/6 mice were purchased from Shanghai Jiesijie experimental animal Co	C57BL/6 suggested: None

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   Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   There are several limitations in our study. First, the total number of patients involved in our clinical trial is relatively insufficient, which requires a larger sample and multi-center clinical study in the future. Second, we did not evaluate whether hymecromone can reduce the mortality rates of COVID-19 patients because of no critical patients in this clinical trial. Third, given that the exact value of hyaluronan may be different using diverse methods, it is necessary to identify the hyaluronan concentration to clinically distinguish the healthy subjects and COVID-19 patients by uniform standard methods. Overall, the increased hyaluronan is significantly correlated with the decreased lymphocytes and pulmonary lesions of COVID-19 patients. Hymecromone administration can markedly improve the clinical manifestations of COVID-19 patients. Thus, hymecromone could be a potential and efficient drug for COVID-19 therapy, which is needed to further clarify the effect of hymecromone on COVID-19 in a larger sample of clinical trials. Our findings highlight that inhibiting the synthesis of hyaluronan with specific drugs is a promising therapeutic strategy for COVID-19.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   Results from rtransparent:

   • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a protocol registration statement.

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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2021.10.19.21263786v1 on medRxiv

   Oct 19, 2021