Doxycycline in COVID-19: Learnings from the Asian Experience
Written By : Dr. Kamal Kant Kohli
Published On 2020-10-29 04:58 GMT | Update On 2021-02-05 09:33 GMT
Coronavirus disease 2019 (COVID19) : A World Health Organisation (WHO) declared global pandemic, has infected over millions of people by severe acute respiratory syndrome‐coronavirus‐2 (SARS-CoV-2), and billions have become victims of its direct and indirect socioeconomic squeal. While the efforts in the direction of vaccine development are yet to meet success, there are no well- established treatment options available. Early treatment, before the disease becomes severe, would be optimal. (1) Along with this objective, one of the emerging therapeutic candidates, Doxycycline, is a potent antimicrobial with both antiviral and anti-inflammatory activities. (2) The pandemic has manifested a diverse spectrum globally and it may be interesting to review the Asian experience with the use of Doxycycline in clinical practice settings for the management of COVID-19 infection.
Doxycycline added as Combination in Mild to Moderate COVID-19 Infections
A study was conducted to investigate and compare the clinical outcomes of Doxycycline-Ivermectin versus. Hydroxychloroquine-Azithromycin combination therapy COVID19 patients with mild to moderate COVID-19 infection. In a modest clinical setting in Bangladesh, Patients were segmented randomly into two groups: The first group received Ivermectin 200μgm/kg single dose plus Doxycycline 100 mg BID for 10 days, while the second group received Hydroxychloroquine 400mg 1st day, followed by 200mg BID for 9 days plus Azithromycin 500mg daily for 5 days
Doxycycline Treatment across a heterogeneous patient profile
The total number of patients enrolled in the study was 116 - 90 males and 26 females, covering a broad age group ranging from 16 to 80 years, with a mean age of 34 years. The Doxycycline- Ivermectin consisted of 43 males and 17 females, aged 35.72 ± 15.1 years; while the Hydroxychloroquine + Azithromycin treatment arm formed of 47 males and 9 females, with a mean age of 32 years.
Out of the total, 91 patients were symptomatic, while 25 were asymptomatic patients with a history of contact.
Outcomes after Treatment
Polymerase chain reaction (PCR) for SARS-CoV-2 was repeated in all symptomatic patients, on the second day onward without symptoms, or, for those who were asymptomatic throughout the study, on the 5th day after taking medication and repeated every two days onward if the result is positive. Time to negative PCR and time to full symptomatic recovery was measured for each group
Faster Recovery with Doxycycline Based Combination
All subjects in the Doxycycline- Ivermectin group reached a negative PCR for SARS-CoV-2, at a mean period of 8.93 days, and all reached symptomatic recovery, at a mean duration of 5.93 days, with 55.10% symptom-free by the 5th day. In the Hydroxychloroquine-Azithromycin group, 96.36% reached a negative PCR at a mean of 9.33 days and were symptom-free at a mean period of 6.99 days.
The Doxycycline- Ivermectin based combination showed a trend toward superiority to the Hydroxychloroquine-Azithromycin therapy in patients with mild to moderate COVID19 disease.
Summarizing the Asian Experience
Doxycycline is a tetracycline-class of antimicrobial agents, which acts via the inhibition of bacterial ribosomes. It is a well-tolerated bacteriostatic drug which a well-recognized history of clinical use. (3) The efficacy and tolerability of Doxycycline and Ivermectin are established in combination with an earlier study for the treatment of onchocerciasis. (4) Several recent studies have suggested a therapeutic role of Doxycycline against COVID-19. (5)
In yet another published case series on 100 patients with COVID-19 treated with a combination of doxycycline and Ivermectin, concluded the treatment to be very effective in viral clearance in mild and moderately sick COVID-19 patients, with all patients tested negative and their symptoms improved within 72 hours without any noticeable side effects.
Such studies have cited that using doxycycline-based combination therapies within the first few days of being positive with or without symptoms may save the hospital admissions of that 20% who suffer and the unnecessary deaths whilst on ventilators. The community transmission by asymptomatic carriers can be halted by treating these asymptomatic COVID-19 positive patients. Importantly, it is a cost-effective option, and seems suitable for use, specifically for low resource Asian settings. (6)
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References
Adapted from
1 Abu Taiub Mohammed Mohiuddin Chowdhury et al, A comparative study on Ivermectin- Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients, DOI: 10.13140/RG.2.2.22193.81767/3
2 Ismail Anwar , Eman Kamal El-dien Anwer & Mohamed AbdAllah (2020) Doxycycline: a new treatment option for COVID-19, Alexandria Journal of Medicine, 56:1, 130-131, DOI: 10.1080/20905068.2020.1790957
3 Holmes, Natasha E., and Patrick G. Charles. "Safety and Efficacy Review of Doxycycline." Clinical Medicine Insights: Therapeutics, vol. 1, 2009, pp. 471-482
4 Abegunde, Ayokunle T., et al. "Doxycycline plus ivermectin versus ivermectin alone for treatment of patients with onchocerciasis." Cochrane Database of Systematic Reviews, no. 1, 2016, p. CD011146.
5 Conforti, Claudio, et al. "Doxycycline, a widely used antibiotic in dermatology with a possible anti‐inflammatory action against IL‐6 in COVID‐19 outbreak."Dermatologic Therapy, 2020, p. e13437
6 M Alam et al, A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline, Journal of Bangladesh College of Physicians and Surgeons 2020;38:10-15
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