4.3 Article

Sequential doxycycline and colchicine combination therapy in Covid-19: The salutary effects

Journal

PULMONARY PHARMACOLOGY & THERAPEUTICS
Volume 67, Issue -, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2021.102008

Keywords

COVID-19; SARS-CoV-2; Colchicine; Doxycycline; Clinical outcomes

Funding

  1. Portuguese Foundation for Science and Technology under the Horizon 2020 Program [PTDC/PSI-GER/28076/2017]
  2. Fundação para a Ciência e a Tecnologia [PTDC/PSI-GER/28076/2017] Funding Source: FCT

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COVID-19, caused by SARS-CoV-2, is a global pandemic with complications including acute lung injury and acute respiratory distress syndrome due to exaggerated immune response. A series of case reports showed marked improvements in symptoms, clinical, and radiological outcomes in COVID-19 pneumonia patients treated with a combination of doxycycline and colchicine, suggesting the need for large-scale prospective studies.
Coronavirus virus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), actually considered as a global pandemic. The entry-point for SARS-CoV2 is angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4), which are highly expressed in the lung. Among other complications, COVID-19leads to fatal pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to development of cytokine storm (CS). The pathogenesis of SARSCoV-2 infection depends on the viral load and human innate/adaptive immune response that are required for viral elimination in the first phase of COVID-19. However, an exaggerated immune response in the second phase of COVID-19 results in immune overreaction and CS-induced ALI and ARDS. Thus, in view of these considerations, we report here a series of five patients with COVID-19 pneumonia who developed ALI. In addition to the supportive therapy, the patients received doxycycline in the first week and doxycycline plus colchicine in the second week. Following sequential therapy with doxycycline and/or colchicine in patients with COVID-19 pneumonia, the patients had reduction of disease severity and symptoms with better clinical and radiological outcomes. However, it is tough to confirm the link between this therapeutic combination and recovery from COVID-19 pneumonia, as it is a small case-series report. Nevertheless, this study gives a rational for large-scale prospective studies to evaluate the dual sequential effect of doxycycline and colchicine on the COVID-19 severity. This case-series illustrated that use of colchicine: doxycycline combination is linked with marked improvements in the clinical, laboratory and radiological outcomes in patients with COVID-19 pneumonia. However, we cannot sketch any definitive conclusion from our observation, despite we hypothesize that this combination therapeutic regimen may attenuate and treat COVID-19. Further, namely prospective, randomized, and controlled clinical studies are recommended in this regard.

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