Antibiotic Management in Covid-19: Scope of Doxycycline

Written By :  Dr. Kamal Kant Kohli
Published On 2020-09-04 06:00 GMT   |   Update On 2020-10-26 08:43 GMT

The coronavirus disease 2019 (COVID-19) pandemic, due to its characteristic novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global sudden and substantial rise in hospitalization burden for pneumonia with multiorgan dysfunction. COVID-19 first recognized in December 2019, when a group of patients with pneumonia of unknown cause was identified in...

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The coronavirus disease 2019 (COVID-19) pandemic, due to its characteristic novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global sudden and substantial rise in hospitalization burden for pneumonia with multiorgan dysfunction. COVID-19 first recognized in December 2019, when a group of patients with pneumonia of unknown cause was identified in Wuhan, China.

Transmission of Coronavirus Disease 2019 (COVID-19)
Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) happens mainly through respiratory droplets from face-to-face contact and, to a lesser degree, via contaminated surfaces. Aerosol spread may likely occur, but the role of such transmission in humans yet remains to be further confirmed. An estimated 48 % to 62% of transmission may occur via pre-symptomatic carriers.
Clinical Features
Common manifestations in hospitalized patients comprise of fever (up to 90%), dry cough (up to 86%), shortness of breath (up to 80%), fatigue (38%), myalgias (up to 44%), nausea/vomiting or diarrhoea (up to 39%), headache, weakness (25%), and rhinorrhea (7%). Anosmia or ageusia may be the sole presenting symptom in approximately 3% of individuals with COVID-19.
Diagnosis
Laboratory abnormalities indicate lymphopenia (83%), elevated inflammatory markers (e.g., erythrocyte sedimentation rate, C-reactive protein, ferritin, tumour necrosis factor-α, IL-1, IL-6), and abnormal coagulation parameters (e.g., prolonged prothrombin time, thrombocytopenia, elevated D-dimer and low fibrinogen).
Radiographic findings in patients with COVID-19 include bilateral, lower-lobe predominate infiltrates on chest radiographic imaging and bilateral, peripheral, lower-lobe ground-glass opacities and/or consolidation on chest computed tomographic imaging.
Doxycycline – Potential Choice of Antibiotic
While selecting an antibiotic, Doxycycline is cited as a potential partner in COVID-19 treatment armamentarium because of its anti-viral and anti-inflammatory effects, microbiological coverage against atypical bacterial pneumonia, and alleviating the lung sequel complications associated with COVID-19.
This is further substantiated by a recently published Asian observational study, bringing out real-life management strategy of COVID-19 Patients at a tertiary centre in Bangladesh, cited the use of Doxycycline, given at a dose of 100 mg, twice daily for 10 days added to standard care, resulting in favourable outcomes, acceptable recovery at the time of discharge and no mortality. 
Scope of Doxycycline – Clinical Pointers in COVID-19 Management Armamentarium
√ Doxycycline is a broad-spectrum antibiotic with unique anti-inflammatory activity, pertinent to the pathophysiology of COVID-19.
√ Doxycycline possesses anti-viral properties; in-vitro studies indicating antiviral activity of against SARS-CoV-2  and potential role in overcoming respiratory distress sequels.
√ Doxycycline acts on the interleukin-6 (IL-6) pathway, thus may help in mitigating the cytokine storm which influences clinical outcomes in COVID-19. Doxycycline has proven efficacy in improving clinical outcomes in dengue, where it reduced inflammatory cytokines and improved mortality outcomes.
√ Doxycycline has endorsements for empirical use as one of the choices of antibiotics from certain global guidelines for the management of COVID-19.
√ Evidence from published scientific papers indicates the use of oral doxycycline 100 mg twice daily for 5-10 days in the treatment of COVID-19 patients.
√ Much relevant in the Indian practice settings, doxycycline is inexpensive, safe and easily available, garnering additional testimony from benefitting COVID-19 patients in a recently published Asian evidence.
Summary
While the vaccine is a few weeks to months away, and treatment modalities continue to evolve through the spectacle of emerging evidence and clinical experiences, doxycycline emerges as a promising consideration through multiple perspectives of scientific reasoning for use in the management of COVID- 19 – mechanistic, clinical benefits, past experiences, guideline recommendations, and meeting the Indian patient-centric feasibilities relevant in the real world practice settings.
References 
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2. Ganyani T, Kremer C, Chen D, et al. Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020. Euro Surveill. 2020;25(17). doi:10.2807/ 1560-7917.ES.2020.25.17.2000257
3. Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020; 5(7):667-678. doi:10.1016/S2468-1253(20)30126-6
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6. Faizul Huq A, Rahman MF, Islam MA, et al. Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study. Euroasian J Hepatogastroenterol. 2020;10(1):31-35. doi:10.5005/jp-journals-10018-1316
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8. In vitro antiviral activity of doxycycline against SARS-CoV-2 – IHU. [cited 2020 Apr 23]. Available from: https://www.mediterranee-infection.com/invitro- antiviral-activity-of-doxycycline-against-sars-cov-2
9. Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020, doi:http://dx.doi.org/10.1016/j.apsb.2020.02.008.
10. Fredeking TM, Castro JEZ, Vado-Solis I, Perez-Osorio C. Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever. Clin Dev Immunol 2011, doi:http://dx.doi.org/10.1155/2011/370872.
11. COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital, NICE guideline Published: 1 May 2020 www.nice.org.uk/guidance/ng173
12. Massachusetts General Hospital (MGH) COVID-19 Treatment Guidance, July 2020, Version 6.1 7/1/2020

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