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| CORRESPONDENCE |
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| Year : 2020 | Volume
: 152
| Issue : 1 | Page : 144-145 |
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Authors' response
Pranab Chatterjee1, Tanu Anand2, Kh Jitenkumar Singh3, Reeta Rasaily4, Ravinder Singh5, Santasabuj Das6, Harpreet Singh7, Ira Praharaj8, Raman R Gangakhedkar8, Balram Bhargava9, Samiran Panda10
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 Publication | 04-Aug-2020 |
Correspondence Address:
Samiran Panda
ICMR-National AIDS Research Institute, Pune, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
Read associated with this article DOI: 10.4103/0971-5916.291398
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;152:144-5 |
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 Sep 16];152:144-5. Available from: https://www.ijmr.org.in/text.asp?2020/152/1/144/291398 |
We thank the authors of the letter for their critical reading of our case-control investigation[1]. During this investigation, we matched the cases and controls by time and location using the date of testing and laboratory where they were tested following the development of symptoms of respiratory tract infection, to limit the variability between cases and controls. The overall purpose of our investigation was to identify factors associated with SARS-CoV-2 infection (protective or risk posing). However, we realize that examining the safety and efficacy of pre-exposure prophylaxis, based on hydroxychloroquine (HCQ), would require clinical trials as indicated in the discussion section of our article[1].
Chloroquine (CQ) and HCQ are known to have extensive tissue spread, resulting in a large volume of distribution in the human body. Single-dose kinetics studies in the context of malaria chemoprophylaxis show that adequate plasma levels of chloroquine may be achieved only after four weeks. During this period, the individual taking CQ prophylaxis may not achieve the desired plasma concentration of the drug needed for protection[2]. These findings prompted the recommendation that CQ prophylaxis in malaria-naïve travellers be initiated at least two weeks prior to entry into malaria-endemic areas. Interestingly, our study also provided a similar hint of protection against SARS-CoV-2 infection obtained through HCQ chemoprophylaxis, where a dose-response relationship appeared unfolding after the intake of four or more maintenance doses following the initial loading dose.
Importantly, although CQ and HCQ are efficiently concentrated in lung tissue over time, reaching at least 11.8 times the concentration in plasma, in vivo concentrations needed to counter SARS-CoV-2 infection, may be achieved in a dose-dependent manner[3],[4]. For a drug like HCQ where lysosomal sequestration is known and can lead to variable concentrations in various body tissues compared to plasma levels[5], information regarding HCQ levels, specifically in lung tissues, is important as far as the activity against SARS-CoV-2 and other respiratory viruses is concerned. With the current evidence, it is unclear if parameters such as area under the curve (AUC) can be reliably used to predict levels in respiratory tissues and drug efficacy[6].
As our study was specifically conducted to identify the associations between various exposure variables and SARS-CoV-2 infection in symptomatic healthcare workers (HCWs), it would be inappropriate to extrapolate the findings to home-based contacts of confirmed cases of COVID-19. Notwithstanding the findings of our study, we would still like to underscore the necessity of pondering over protective behavioural factors and appropriate use of personal protective equipment along with plausible chemoprophylaxis-based biologic intervention while examining the occurrence of SARS-CoV-2 infection in HCWs.
 References | |  |
| 1. | Chatterjee P, Anand T, Singh Kh, 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. Indian J Med Res 2020; 151 : 459-67.  |
| 2. | Frisk-Holmberg M, Bergqvist Y, Termond E, Domeij-Nyberg B. The single dose kinetics of chloroquine and its major metabolite desethylchloroquine in healthy subjects. Eur J Clin Pharmacol 1984; 26 : 521-30. |
| 3. | Adelusi SA, Salako LA. Kinetics of the distribution and elimination of chloroquine in the rat. Gen Pharmacol 1982; 13 : 433-7. |
| 4. | Smit C, Peeters MYM, van den Anker JN, Knibbe CA. Chloroquine for SARS-CoV-2: Implications of Its unique pharmacokinetic and safety properties. Clin Pharmacokinet 2020; 59 : 659-69. |
| 5. | Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther 2018; 365 : 447-59. |
| 6. | Arnold SL, Buckner F. Hydroxychloroquine for treatment of SARS-CoV-2 Infection? Improving our confidence in a model-based approach to dose selection. Clin Transl Sci 2020; 13 : 642-5. |
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