Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels

Fredeking, Terry; Zavala-Castro, Jorge; González-Martínez, Pedro; Moguel-Rodríguez, William; Sanchez, E. Corona; Foster, Michael J.; Díaz-Quijano, Fredi Alexander

doi:10.2174/1574891x10666150410153839

Cited by 70 publications

(49 citation statements)

References 24 publications

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“…Although cephazolin and cephalexin have been proved in animal models for Leptospira treatment, apparently with good response, currently, they are not the treatment of choice [26,27]. Doxycycline, which is among the preferred antibiotic therapy, has showed reduction of chikungunya virus replication and reduction in serum levels of IL-6, TNF and mortality in in-vitro and clinical studies [28][29][30]. Since antibiotic therapy in leptospirosis is open to discussion because the lack of conclusive evidence of its benefits, especially penicillin in severe disease [27].…”

Section: Discussionmentioning

confidence: 99%

Fatal Dengue, Chikungunya and Leptospirosis Co-Infection: The Febrile Patient in Tropical Areas, Importance of Co-Infection Assessment

Cardona-Ospina¹,

Ce²,

Vásquez-Serna³

et al. 2018

Preprint

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Background: The febrile patient from tropical areas, in which emerging arboviruses are endemic, represent a diagnostic challenge and potential co-infections with other pathogens (i.e bacteria or parasites) are usually overlooked. Objectives: We present a case of an elderly woman diagnosed with dengue, chikungunya and Leptospira interrogans co-infection. Study Design: Case report. Results: An 87-year old woman from Colombia complained of upper abdominal pain, arthralgia, myalgia, hyporexia, malaise and intermittent fever accompanied with progressive jaundice. She had a medical history of chronic heart failure (Stage C, NYHA III), without documented cardiac murmurs, right bundle branch block, non-valvular atrial fibrillation, hypertension, and chronic venous disease. Her cardiac and pulmonary status quickly deteriorated after 24 hours of her admission without electrocardiographic changes and she required ventilatory and vasopressor support. In the next hours the patient evolved to pulseless electrical activity and then she died. Dengue IgM, NS1 ELISA, MAT for Leptospira interrogans and RT-PCR for chikungunya, were positive. Discussion: This case illustrates a multiple co-infection in a febrile patient from a tropical area of Latin America that evolved to death.

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Section: Discussionmentioning

confidence: 99%

Fatal Dengue, Chikungunya and Leptospirosis Co-Infection: The Febrile Patient in Tropical Areas, Importance of Co-Infection Assessment

Cardona-Ospina¹,

Ce²,

Vásquez-Serna³

et al. 2018

Preprint

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“…Moreover, based on molecular docking and dynamic studies, minocycline was proposed as potential antiviral therapy against Congo Crimean hemorrhagic fever virus to inhibit the binding of virus to host nucleoprotein [57]. In a randomized controlled trial of dengue hemorrhagic fever patients, compared with standard-of-care, combination therapy with doxycycline (analogue of minocycline) signi cantly decreased the TNF and IL-6 levels, and mortality [58].…”

Section: Biological Activities Of Minocyclinementioning

confidence: 99%

Minocycline Might Be an Adjunctive Therapy Option for the Treatment of COVID-19: In Silico Screening, Structure-affinity Relationship, and Literature Review

Xiao¹

2020

Preprint

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Abstract Up to now, there is no specific therapy for the globally ongoing COVID-19. To explore potential inhibitors of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) for the treatment of novel coronavirus disease (COVID-19), in silico screening of 135 clinical drugs was performed targeting on 3-chymotrypsin-like protease (3CLpro, or M pro ). Six drugs including anti-HIV drug (raltegravir), antibacterial drugs (cefonicid, cefoperazone, minocycline), and antidiabetic drugs (canaglifozin, glyburide) showed high binding affinities (≤ -8.5 kcal/mol) and interesting binding conformations compared with the designed co-crystal ligand N3 (-7.7 kcal/mol). In which the antibiotic minocycline, an inhibitor of bacterial ribosomal rRNA, showed the highest binding affinity (-9.6 kcal/mol). Valuable hydrogen bonding and hydrophobic interactions were found between minocycline and Mpro active site. Beside the hydrogen bond with Cys145, minocycline formed a Pi-Cation with His41, which strongly supported minocycline as a Michael Addition acceptor to bind with the catalytic site of Mpro . The structure-affinity relationship was studied based on molecular docking of minocycline analogues. Literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad-spectrum of biological markers during minocycline administration were opposed to those of COVID-19 condition (both severe and non-severe). Minocycline deserves in vitro and in vivo evaluations as SARS-CoV-2 inhibitor as well as a randomized controlled trial to investigate the efficacy for COVID-19. These studies will shed new light on an adjuvant treatment strategy for this potentially lethal viral disease.

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“…It is hypothesised that with doxycycline, this rate would increase to 12%. Indeed, the article concerning the effect of doxycycline on dengue patients: "Dengue Patients Treated With Doxycycline Showed Lower Mortality Associated with a Reduction in IL-6 and TNF Levels" [48], shows that the group on doxycycline has a lower mortality than those in the untreated group (11.2% [13/116] vs 20.9% [24/115], respectively, p=0.05). In addition, doxycycline administration resulted in a signi cant drop in IL6 and TNF.…”

Section: Sample Sizementioning

confidence: 99%

Impact of Doxycycline on Covid-19 Patients With Risk Factors of Disease Degradation: Dynamic, A Randomised Controlled Double-blind Trial

Poinas

Boutoille

Vrignaud

et al. 2020

Preprint

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Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from metalloproteases (MMPs). It is possible that their chelating activity may help to inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. The lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among tetracyclines, the advantages of doxycycline are triple: its long history of safety (infrequent side effects with no notable risks), the short duration of treatment and its low cost.Methods: By estimating the rate of patients presenting pulmonary signs requiring hospitalisation in at-risk patients infected with COVID-19 at 25%, we hypothesise that on doxycycline, this rate would decrease to 12%. The main objective involves 2 embedded hypotheses tested successively in case of rejection of the previous one: (i) Decrease the rate of patients requiring hospitalisation, (ii) Decrease the use of mechanical ventilatory assistance.Discussion: This study could have an impact on the management of COVID-19 risk factor patientsupstream of hospitals by general practitioners. These patients,if kept at home under experimental treatment, would participate in reducing the risk of dissemination of SAR-CoV-2in the population.Thus, this treatment would contribute to supporting the deconfinement strategy through blocking the viral infection early and reducing the contagious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.

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Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels

Abstract: The above findings suggest that doxycycline can provide a clinical benefit to dengue patients at high risk of complications. This effect could be mediated by decreasing pro-inflammatory cytokine levels.

Cited by 70 publications

References 24 publications

Fatal Dengue, Chikungunya and Leptospirosis Co-Infection: The Febrile Patient in Tropical Areas, Importance of Co-Infection Assessment

Fatal Dengue, Chikungunya and Leptospirosis Co-Infection: The Febrile Patient in Tropical Areas, Importance of Co-Infection Assessment

Minocycline Might Be an Adjunctive Therapy Option for the Treatment of COVID-19: In Silico Screening, Structure-affinity Relationship, and Literature Review

Impact of Doxycycline on Covid-19 Patients With Risk Factors of Disease Degradation: Dynamic, A Randomised Controlled Double-blind Trial

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