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   Table of Contents      
CORRESPONDENCE
Year : 2020  |  Volume : 152  |  Issue : 1  |  Page : 122-123

Authors' response


1 Translational Global Health Policy Research Cell, New Delhi, India
2 Multidisciplinary Research Unit/Model Rural Health Research Unit, New Delhi, India
3 ICMR-National Institute of Medical Statistics, New Delhi, India
4 Division of Reproductive Biology, Maternal Health & Child Health, New Delhi, India
5 Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
6 Division of Clinical Medicine, ICMR-National Institute of Cholera & Enteric Diseases, Kolkata, West Bengal, India
7 Informatics, Systems & Research Management Cell, Indian Council of Medical Research, New Delhi, India
8 Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, New Delhi, India
9 Department of Health Research, Ministry of Health & Family Welfare; Indian Council of Medical Research, New Delhi, India
10 ICMR-National AIDS Research Institute, Pune, Maharashtra, India

Date of Web Publication17-Jul-2020

Correspondence Address:
Samiran Panda
ICMR-National AIDS Research Institute, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


Read associated with this article

DOI: 10.4103/0971-5916.290075

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How to cite this article:
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, Panda S. Authors' response. Indian J Med Res 2020;152:122-3

How to cite this URL:
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, Panda S. Authors' response. Indian J Med Res [serial online] 2020 [cited 2021 Apr 18];152:122-3. Available from: https://www.ijmr.org.in/text.asp?2020/152/1/122/290075

We thank the authors[1] for their interest in the case-control investigation[2] we conducted and also acknowledge the importance of using preventive strategies, such as social distancing and utilization of personal protective equipment for preventing SARS-CoV-2 infection in healthcare workers. They mention that the previous in vitro experiments with quaternary ammonium compounds such as ammonium chloride have documented an increase in endosomal p H in specific cell lines as is observed with hydroxychloroquine (HCQ). However, we would like to emphasize that the referred study reported on SARS-CoV, not on SARS-CoV-2[3]. It is also vital to consider that the stated evidence is derived from an in vitro study, which has shown increased antibody-mediated infection of specific cell lines expressing Fc receptors in the presence of ammonium chloride. But importantly, the antibody-dependent enhancement (ADE) only led to abortive infection in the experiments described in the quoted article. In addition, the increase in infection was only seen in the ADE pathway and not in the angiotensin-converting enzyme 2 (ACE2) receptor pathway. For SARS-CoV-2, while the ACE2 receptor pathway has been shown to be relevant, the importance of ADE pathway is not clear[4]. Contrary to the claim by authors[1], the in vitro results for the effect of ammonium chloride on in vitro infection for SARS-CoV in the quoted study did not biologically explain why short duration of HCQ should increase the risk of infection for SARS-CoV-2. The extrapolation to our study therefore, seems inappropriate.

The authors[1] have suggested an alternate dosing schedule for prophylaxis, which is higher than the current schedule. Before any such changes in the dosing schedule are considered, the safety of the proposed schedule must be proven through clinical studies. The pharmacological activity of HCQ against SARS-CoV-2 has been assessed in vitro, and the loading dose of 400 mg twice daily followed by twice daily maintenance dose of 200 mg has been assessed in physiology-based pharmacokinetics (PBPK) models for concentrations in the lungs[5]. Further, models describing the highly compartmentalized distribution of chloroquine in humans have been developed, which show that if the prophylactic effect is considered to be based on the pulmonary exposure of HCQ, then once weekly dosing could prove effective[6]. We agree that the dosing schedule suggested by the authors[1] should be based on the available in vitro or in vivo data derived from PBPK models or on clinical studies of safety and efficacy.

 
   References Top

1.
Tirlangi P, Khan AR, Desai D, Soneja M. False reassurance or inadequate drug levels? IndianJ Med Res 2020; 152 : 121-2.  Back to cited text no. 1
    
2.
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, et al. Healthcare workers and SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. IndianJ Med Res 2020; 151 : 459-67.  Back to cited text no. 2
    
3.
Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F,et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway. J Virol 2011; 85 : 10582-97.  Back to cited text no. 3
    
4.
Hui KP, Cheung MC, Perera RA, Ng KC, Bui CH, Ho JC, et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: An analysis in ex vivo and in vitro cultures. Lancet RespirMed 2020; 8 : 687-95.  Back to cited text no. 4
    
5.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; ciaa237.  Back to cited text no. 5
    
6.
Aljayyoussi G, Rajoli R, Pertinez H, Pennington SH, Hong WD, O'Neill PM, et al. Modelling of systemic versus pulmonary chloroquine exposure in man for COVID-19 dose selection. medRxiv 2020. doi: 2020.04.24.20078741.  Back to cited text no. 6
    




 

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