Clinical evidence
Overall, whilst tetracycline’s direct anti-viral activity against
SARS-CoV2 is not yet strongly supported by experimental data, their
above described beneficial mechanisms in ARDS can be directly translated
to COVID-19-induced ARDS. Furthermore, our hypothesis of the therapeutic
potential of repurposing tetracyclines for COVID-19 treatment is getting
the support of the clinical reports published up to date. These are
scarce, but positive and promising. For example, rapid clinical
improvement was reported in 4 high risk COVID-19 patients after
doxycycline treatment (Yates et al., 2020). A multicenter prospective
observational study including 38 COVID-19 patients treated with
tetracyclines reported a remarkable resolution of mild symptoms within
the first week of treatment (Gironi et al., 2020). In a larger study,
early treatment with doxycycline in 89 high-risk COVID-19 patients was
associated with early clinical recovery, decreased hospitalization and
decreased mortality (Alam et al., 2020). Furthermore, doxycycline has
been used for COVID-19 treatment in combination with hydroxychloroquine
or lopinavir, reporting an overall 4.2% fatality rate vs 27% and 23%
for monotherapy, respectively (Cag et al., 2021). In another study, in
combination with ivermectin, doxycycline helped to reduce disease
progression and the time to recovery in patients with severe COVID-19.
The mortality rate was also reduced from 22.72% to 0% compared to
standard care with azithromycin (Hashim et al., 2020). Altogether, we
believe that these reports provide sufficient clinical evidence to
support the inclusion of tetracyclines in ARDS and COVID-19 therapeutic
management.