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Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro

Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (date from preprint)
Mar 2020  
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In Vitro study showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells.
Clementi et al., 31 Mar 2020, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro
Nicola Clementi, Elena Criscuolo, Roberta Antonia Diotti, Roberto Ferrarese, Matteo Castelli, Lorenzo Dagna, Roberto Burioni, Massimo Clementi, Nicasio Mancini
Frontiers in Microbiology, doi:10.3389/fmicb.2020.01704
While the SARS-CoV-2 pandemic is heavily hitting the world, it is of extreme importance that significant in vitro observations guide the quick set up of clinical trials. In this study, we evidence that the anti-SARS-CoV2 activity of a clinically achievable hydroxychloroquine concentration is maximized only when administered before and after the infection of Vero E6 and Caco-2 cells. This suggests that only a combined prophylactic and therapeutic use of hydroxychloroquine may be effective in limiting viral replication in patients.
ETHICS STATEMENT The study involving human participants was reviewed and approved by Ospedale San Raffaele IRB in the COVID-19 Biobanking project. The patient from whose samples the virus was isolated provided written informed consent. AUTHOR'S NOTE This manuscript has been released as a pre-print at bioRxiv preprint. doi: 10.1101/2020.03.29.014407, Hu et al. (2020) . AUTHOR CONTRIBUTIONS NC and NM conceived the study. EC, RD, and RF performed the experiments. NC, NM, EC, MCa, and MCl analyzed the data. NC, NM, EC, and RD wrote the manuscript. NC, NM, LD, RB, and MCl revised the manuscript. All authors contributed to the article and approved the submitted version. coronavirus (2019-nCoV) in vitro. Cell Res. 30, 1-3. doi: 10.1038/s41422-020-0282-0 Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., et al. (2020) . In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect. Dis. doi: 10.1093/cid/ciaa237. [Epub ahead of print]. Zhou, D., Dai, S.-M., and Tong, Q. (2020). COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J. Antimicrob. Chemother. 63, 457-454. doi: 10.1093/jac/ dkaa114 Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest...
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