A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation: in vitro evidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients
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Abstract
The need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant ( Thymbra capitata (L.) Cav., Salvia fruticosa Mill. and Origanum dictamnus L.) essential oil mixture (CAPeo) has a remarkable in vitro antiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans ( NCT04705753 ).
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SciScore for 10.1101/2021.01.11.20248947: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: The study received approval by the University of Crete Bioethics Committee (No 78/01.04.2020). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and virus titration: SARS -CoV-2 (isolate 30-287) was obtained through culture in Vero E6 cells, from an infected patient, in Alexandroupolis, Greece. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Statistical analysis: Data were analyzed using the SPSS software (IBM SPSS Statistics for Windows, Version 26.0 … SciScore for 10.1101/2021.01.11.20248947: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: The study received approval by the University of Crete Bioethics Committee (No 78/01.04.2020). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and virus titration: SARS -CoV-2 (isolate 30-287) was obtained through culture in Vero E6 cells, from an infected patient, in Alexandroupolis, Greece. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Statistical analysis: Data were analyzed using the SPSS software (IBM SPSS Statistics for Windows, Version 26.0 Armonk SPSSsuggested: (SPSS, RRID:SCR_002865)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).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:A concrete limitation of this study is that we do not have a control group; we have therefore compared the evolution of disease symptoms with the few studies reporting the evolution of symptoms in non-hospitalized patients (Allen et al., 2020;Tenforde et al., 2020). As discussed previously (Allen et al., 2020;Lechien et al., 2020), symptoms may vary significantly, related to the ethnicity of participants. At the beginning of the study (patient consultation and positive real-time PCR result), the main general symptoms include headache, myalgia, weakness and fever, in accord with previous investigations (Allen et al., 2020;Lechien et al., 2020;Tenforde et al., 2020). However, in our group, fever was low <37.5°C in all but one patient, and the frequency and severity of other symptoms, such as gastrointestinal (diarrhea, respiratory and ENT symptoms were low, possibly because of the low viral load, but without excluding the possibility of simply witnessing an effect prevalent simply because of the small group size. Symptoms evolution was compared to that reported symptoms at days 1 and 14, by (Tenforde et al., 2020) and (Allen et al., 2020), including a larger number of cases, in which symptoms were self-reported, daily, but without the participation of a medical examiner. In our group, treated with CAPeo, we report a complete resolution of headache, fatigue and fever, major general symptoms in COVID-19. In contrast, headache, and fatigue persisted in the studies of (Allen et al....
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04705753 Completed Assessment of the Clinical Effectiveness of a Herbal Extract… 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).
Results from JetFighter: We did not find any issues relating to colormaps.
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.
- No protocol registration statement was detected.
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