Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

Abstract

Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19–related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.

COVID -19: Case report of assertive treatment in diabetic patients

“…In addition to their anti-inflammatory activity, the potential of tetracyclines to provide a prophylactic benefit in reducing ventilatory support and the length of ICU stay for patients with ARDS (acute respiratory distress syndrome) associated with Sars-Cov-2 infection was evident. Tetracyclines are lipophilic and therefore easily penetrate lung tissues where they inhibit viral replication [26].…”

Doxycycline in the Coronavirus Disease 2019 Therapy

“…Hayder M. Al-kuraishy et al 12 indicate tetracyclines as a possible therapy for COVID-19 patients. They emphasise the effectiveness of doxycycline and minocycline in treatment, as well as the synergistic effect with chloroquine.…”

“…It is difficult to unequivocally confirm the effectiveness of the medication in the presented cases, but similar observations were made by other researchers. 3,[9][10][11][12] In the study of Mohammud M. Alam et al, 9 a description of a series of 89 elderly patients with confirmed moderate to severe COVID-19 with concomitant diseases was presented. All patients in this group were treated with doxycycline for 7 days at a dose of 100 mg daily.…”

Evaluation of minocycline combined with favipiravir therapy in coronavirus disease 2019 patients: A case-series study

“…Minocycline (MIN) has been reported to exert anti-inflammatory, immunomodulatory, and antiviral effects in addition to its broad antibacterial activity. The possibility of antiviral activity against SARS-CoV-2 has also been suggested by several researchers [6,7]. The objective of the present study was to investigate the efficacy and safety of combination therapy comprising MIN and FPV.…”