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LETTER TO THE EDITOR
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 1109-1110

The proposed bridging management protocol for COVID-19


1 Department of Medicine, SMS Medical College Hospital, Jaipur, Rajasthan, India
2 Department of Physiology, SMS Medical College Hospital, Jaipur, Rajasthan, India
3 Department of Pharmacology, SMS Medical College Hospital, Jaipur, Rajasthan, India

Date of Submission16-May-2020
Date of Decision06-Jul-2020
Date of Acceptance27-Jul-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Shivankan Kakkar
SMS Medical College Hospital, JLN Road, Jaipur, Rajasthan 302 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_177_2

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How to cite this article:
Bhandari S, Singh A, Sharma R, Mehta S, Dube A, Gupta J, Gupta K, Tak A, Kakkar S. The proposed bridging management protocol for COVID-19. Menoufia Med J 2020;33:1109-10

How to cite this URL:
Bhandari S, Singh A, Sharma R, Mehta S, Dube A, Gupta J, Gupta K, Tak A, Kakkar S. The proposed bridging management protocol for COVID-19. Menoufia Med J [serial online] 2020 [cited 2020 Oct 29];33:1109-10. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/1109/296653



Abstract

SARS-CoV-2, the coronavirus family virus, has ravaged the very fabric of human society, threatening the survival of humans. It has a propensity to access pulmonary portal via angiotensin-converting enzyme receptor 2 (ACE2) or basigin-mediated entry [1] and has four structural proteins, namely, S (spike), E (envelope), M (membrane), and N (nucleocapsid) [2]. The entry of virus is also facilitated by proteases of host cells. Considering the entry of virus and its initiation into host cell through proteases, the concept of designing a definitive management protocol primarily targeting the entry point and protease facilitator was evolved. Subsequently, there has been use of antiretroviral drugs lopinavir–ritonavir, approved for use in patients afflicted with HIV, protease inhibitors (moreover documentation of genome similarity of SARS-CoV-2 with HIV), as well as of hydroxychloroquine (HCQ)owing its inhibitory action on respiratory angiotensin-converting enzyme receptor (ACE2), the portal and receptor of entry of SARS-CoV-2. The aforementioned rationale was instrumental in designing a probable definitive management protocol with the aim of decreasing the chances and/or inhibiting entry of virus through use of HCQ and inhibitors of protease axes, namely, lopinavir–ritonavir, which influences unfolding of virion RNA that conclusively stimulates the cell to amplify and excrete the virion particle.

The combination management protocol of HCQand lopinavir–ritonavir designed according to severity score of COVID-19-positive patients, so adopted at COVID-19 center of S.M.S. Medical College Hospital, Jaipur, has given some encouraging results as of this date of May 9, 2020. The COVID-19 study by Geleris et al. [3] concluded that HCQ does not greatly lower or increase the risk of a composite end point. Currently, this is being observed by clinicians the world over. A combination therapy seemed only logical. It can be employed until a specific management protocol evolves or breakthrough occurs. The HCQ and lopinavir–ritonavir regimen was run on 22 patients with following clinical features:

  1. Age between 30 and 60 years (except for two patients of 64 years of age)
  2. Moderate to severe symptomatology of COVID-19
  3. Pulmonary infiltrations in form of pneumonia, with a CT score of 13
  4. Raised levels of D-dimer and ferritin in serum
  5. Relative low lymphocyte counts
  6. ECG did not document QT elongation
  7. Average duration of RT-PCR test for SARS-CoV-2 being negative since the time of being detected was 8 days as against 10–12 days among nonusers with standard of care only.


Considering the above and the ruthless and relentless course of COVID-19, it is submitted that the aforementioned regimen protocol of HCQ and lopinavir–ritonavir tailor-made as per se verity score of COVID-19 and the precarious condition when a COVID-19-positive patient mandates a 24 h constant professional vigil (a situation that is too demanding and not practically viable), the following demands attention and diligence with utmost care and caution being observed in welfare of the patient.

Recently, an article by Hung et al. [4] described that a triple antiviral therapy involving the combination of interferon-β-1b, lopinavir–ritonavir, and ribavirin was safe and superior in treatment of mild to moderate Covid-19. However, the study by Chong et al. [5] showed that potentially significant cardiac adverse effects were common in patients treated with HCQ add on therapy to lopinavir–ritonavir. It may be pertinent to mention that most medications currently in use for COVID-19 (i.e. HCQ, chloroquine, lopinavir–ritonavir, and azithromycin) all are associated with QTc prolongation. It has been recommended by Sarma et al. [6], that ECG monitoring is essential in a patient with COVID-19 with pre-existing cardiac morbidity. Nonetheless in the absence of a definitive protocol, there is a need of additional trials for combination therapy of antiviral drugs in patients with COVID-19.

'Till a specific antiviral agent is discovered that inhibits the entry and restricts the unfolding of virion and its replication, the dictum of present times, withstanding its vicissitudes, is a regimen of HCQ and lopinavir–ritonavir, tailor-made to severity score of COVID-19, and is the most logical bridge providing the essential scaffold for tomorrow's definitive anti-COVID-19 management protocol'.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the perfusion conformation. Science 2020; 367:1260–1263.  Back to cited text no. 1
    
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Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020; 10:766–788. doi: 10.1016/j.apsb.2020.02.008.  Back to cited text no. 2
    
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Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020;382:2411–2418. DOI: 10.1056/NEJMoa2012410.  Back to cited text no. 3
    
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Hung IF-N, Lung K-C, Tso EY-K, Liu R, Chung TW-H, Chu M-Y, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. The Lancet 2020; 395:1695–1704. DOI: https://doi.org/10.1016/S0140-6736(20)31042-4.  Back to cited text no. 4
    
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Chong VH, Chong PL, Metussin D, Asli R, Momin RN, Mani BI, et al. Conduction abnormalities in hydroxychloroquine add on therapy to lopinavir/ritonavir in COVID-19. J Med Virol 2020. [published online ahead of print, 2020 May 13]. doi: 10.1002/jmv.26004.  Back to cited text no. 5
    
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Sarma P, Kaur H, Kumar H, Mahendru D, Avti P, Bhattacharyya A, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis. J Med Virol 2020; 92:776–785. 10.1002/jmv.25898.  Back to cited text no. 6
    




 

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