Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study
Akshay Rao, Sundar Kumar Veluswamy, Banashankari Gunjiganur Shankarappa, Rithika Manjunatha Reddy, Nethravathi Umesh, Lissy John, Lysamma Mathew, Naresh Shetty
Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2015326
Background: Hydroxychloroquine had attracted significant attention in the initial phases of the COVID-19 pandemic but current recommendations do not support its use. However, the evidence against its use as pre-exposure prophylaxis have been of low to moderate quality and have been limited by high risk of bias. Methods: Following institutional ethics committee approval, healthcare workers (n = 1294) completing their first week-long COVID in-patient duty, subsequent institutional quarantine and RT-PCR testing for COVID-19 infection were included for this prospective cohort study. Demographic data, hydroxychloroquine usage and related adverse effects were captured through a 'Caring for the Caregivers' surveillance system. A chi-Square test of independence was used to determine the effect of hydroxychloroquine prophylaxis. Results: Among the 1294 participants (age: 31 ± 7 years, 61% women), 273 (21.1%) healthcare workers used hydroxychloroquine prophylaxis as per Indian Council of Medical Research recommendations and 83/1294 (6.4%) tested positive after their duty. There was no significant difference in COVID-19 incidence between those on hydroxychloroquine prophylaxis and those not on it (5.9% vs 6.6%, χ 2 = 0.177, p = 0.675; RR = 0.89, 95% CI -0.53 to 1.52). There were no significant adverse effects to hydroxychloroquine usage.
Conclusion: This study demonstrated no benefit of hydroxychloroquine prophylaxis and provides quality evidence against its use in COVID-19 prevention.
Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions Concept and design: The study was conceived by N Shetty, A Rao and S Kumar Veluswamy. B Gunjiganur Shankarappa, L John and L Mathew contributed towards the design of the study. Data collection: A Rao, S Kumar Veluswamy. L John, L Mathew, N Umesh and R Manjunatha Reddy contributed towards data collection. Analysis: A Rao and S Kumar Veluswamy analysed the data. Writing: A Rao and S Kumar Veluswamy together wrote the first draft and all authors critically reviewed the manuscript and contributed towards the writing. Approval: All authors read and approved the final version of the manuscript for submission
ORCID Akshay Rao http://orcid.org/0000-0002-4111-5424 Sundar Kumar Veluswamy http://orcid.org/0000-0003-2241-6229
References
Abella, Jolkovsky, Biney, Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a randomized clinical trial, JAMA Intern Med
Andrade, Rangel, Santos, Repurposing approved drugs for guiding COVID-19 prophylaxis: a systematic review, Front Pharmacol
Barnabas, Brown, Bershteyn, Hydroxychloroquine as postexposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 infection: a randomized trial, Ann Intern Med
Bergwerk, Gonen, Lustig, Covid-19 breakthrough infections in vaccinated health care workers, N Engl J Med
Bhattacharya, Chowdhury, Nandi, Pre-exposure hydroxychloroquine prophylaxis for covid-19 in healthcare workers: a retrospective cohort, Int J Res Med Sci
Boulware, Pullen, Bangdiwala, A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19, N Engl J Med
Bourgeault, Maier, Dieleman, The COVID-19 pandemic presents an opportunity to develop more sustainable health workforces, Hum Resour Health
Burki, Global COVID-19 vaccine inequity, Lancet Infect Dis
Cook, Personal protective equipment during the coronavirus disease (COVID) 2019 pandemic -a narrative review, Anaesthesia
Cruciani, Pati, Masiello, Ivermectin for prophylaxis and treatment of COVID-19: a systematic review and meta-analysis, Diagnostics
Cutolo, Paolino, Smith, Evidences for a protective role of vitamin D in COVID-19, RMD Open
Dinesh, Cs, Kaur, Hydroxychloroquine for SARS CoV2 prophylaxis in healthcare workers -a multicentric cohort study assessing effectiveness and safety, J Assoc Physicians India
Grau-Pujol, Camprubí, Marti-Soler, Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: initial results of a double-blind, placebo-controlled randomized clinical trial, Res Square,
doi:10.21203/rs.3.rs-72132/v1Kumar, Kubota, Chernov, Potential role of zinc supplementation in prophylaxis and treatment of COVID-19, Med Hypotheses
Liu, Cao, Xu, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov
Martins-Filho, Ferreira, Heimfarth, Efficacy and safety of hydroxychloroquine as pre-and post-exposure prophylaxis and treatment of COVID-19: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials, Lancet Reg Health Am
Mehra, Ruschitzka, Patel, Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet
Mitjà, Marc, Ubals, A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19, N Engl J Med
Nguyen, Drew, Graham, Coronavirus pandemic epidemiology consortium. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study, Lancet Public Health
Niburski, Niburski, Impact of Trump's promotion of unproven COVID-19 treatments and subsequent internet trends: observational study, J Med Internet Res
Rajasingham, Bangdiwala, Nicol, Hydroxychloroquine as pre-exposure prophylaxis for coronavirus disease 2019 (COVID-19) in healthcare workers: a randomized trial, Clin Infect Dis
Reardon, Flawed ivermectin preprint highlights challenges of COVID drug studies, Nature
Singh, Chauhan, Kakkar, Hydroxychloroquine for the treatment and prophylaxis of COVID-19: the journey so far and the road ahead, Eur J Pharmacol
Stricker, Fesler, Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers from india: a meta-analysis, J Infect Public Health
DOI record:
{
"DOI": "10.1080/14787210.2022.2015326",
"ISSN": [
"1478-7210",
"1744-8336"
],
"URL": "http://dx.doi.org/10.1080/14787210.2022.2015326",
"alternative-id": [
"10.1080/14787210.2022.2015326"
],
"assertion": [
{
"label": "Peer Review Statement",
"name": "peerreview_statement",
"order": 1,
"value": "The publishing and review policy for this title is described in its Aims & Scope."
},
{
"URL": "http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ierz20",
"label": "Aim & Scope",
"name": "aims_and_scope_url",
"order": 2,
"value": "http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ierz20"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Received",
"name": "received",
"order": 0,
"value": "2021-10-24"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Revised",
"name": "revised",
"order": 1,
"value": "2021-11-18"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Accepted",
"name": "accepted",
"order": 2,
"value": "2021-11-22"
},
{
"group": {
"label": "Publication History",
"name": "publication_history"
},
"label": "Published",
"name": "published",
"order": 3,
"value": "2021-12-04"
}
],
"author": [
{
"ORCID": "http://orcid.org/0000-0002-4111-5424",
"affiliation": [
{
"name": "Department of Internal Medicine, MS Ramaiah Medical College"
}
],
"authenticated-orcid": false,
"family": "Rao",
"given": "Akshay",
"sequence": "first"
},
{
"ORCID": "http://orcid.org/0000-0003-2241-6229",
"affiliation": [
{
"name": "Department of Physiotherapy, MS Ramaiah Medical College"
},
{
"name": "Healthy Living for Pandemic Event Protection (HL- PIVOT) network, Chicago, Illinois, USA"
}
],
"authenticated-orcid": false,
"family": "Veluswamy",
"given": "Sundar Kumar",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Microbiology, MS Ramaiah Medical College"
}
],
"family": "Shankarappa",
"given": "Banashankari Gunjiganur",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "MS Ramaiah Medical College"
}
],
"family": "Reddy",
"given": "Rithika Manjunatha",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "MS Ramaiah Medical College Hospital"
}
],
"family": "Umesh",
"given": "Nethravathi",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "MS Ramaiah Medical College Hospital"
}
],
"family": "John",
"given": "Lissy",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "MS Ramaiah Memorial Hospital"
}
],
"family": "Mathew",
"given": "Lysamma",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Caring for the Caregivers Surveillance System, MS Ramaiah Medical College Hospitals"
}
],
"family": "Shetty",
"given": "Naresh",
"sequence": "additional"
}
],
"container-title": [
"Expert Review of Anti-infective Therapy"
],
"content-domain": {
"crossmark-restriction": true,
"domain": [
"www.tandfonline.com"
]
},
"created": {
"date-parts": [
[
2021,
12,
4
]
],
"date-time": "2021-12-04T12:55:16Z",
"timestamp": 1638622516000
},
"deposited": {
"date-parts": [
[
2021,
12,
4
]
],
"date-time": "2021-12-04T12:55:25Z",
"timestamp": 1638622525000
},
"indexed": {
"date-parts": [
[
2021,
12,
5
]
],
"date-time": "2021-12-05T05:47:41Z",
"timestamp": 1638683261871
},
"is-referenced-by-count": 0,
"issn-type": [
{
"type": "print",
"value": "1478-7210"
},
{
"type": "electronic",
"value": "1744-8336"
}
],
"issued": {
"date-parts": [
[
2021,
12,
4
]
]
},
"language": "en",
"link": [
{
"URL": "https://www.tandfonline.com/doi/pdf/10.1080/14787210.2022.2015326",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "301",
"original-title": [],
"prefix": "10.1080",
"published": {
"date-parts": [
[
2021,
12,
4
]
]
},
"published-online": {
"date-parts": [
[
2021,
12,
4
]
]
},
"publisher": "Informa UK Limited",
"reference": [
{
"DOI": "10.1186/s12960-020-00529-0",
"doi-asserted-by": "publisher",
"key": "cit0001"
},
{
"key": "cit0002",
"unstructured": "2. Nguyen LH, Drew DA, Graham MS, et al., Coronavirus Pandemic Epidemiology Consortium. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health. 2020;5:e475-83."
},
{
"DOI": "10.1111/anae.15071",
"doi-asserted-by": "publisher",
"key": "cit0003"
},
{
"DOI": "10.1016/j.mehy.2020.109848",
"doi-asserted-by": "publisher",
"key": "cit0004"
},
{
"DOI": "10.1136/rmdopen-2020-001454",
"doi-asserted-by": "publisher",
"key": "cit0005"
},
{
"DOI": "10.3389/fphar.2020.590598",
"doi-asserted-by": "crossref",
"key": "cit0006",
"unstructured": "6. Andrade BS, Rangel FS, Santos NO, et al. Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review. Front. Pharmacol. 2020;11:590598."
},
{
"DOI": "10.1038/s41421-020-0156-0",
"doi-asserted-by": "publisher",
"key": "cit0007"
},
{
"DOI": "10.2196/20044",
"doi-asserted-by": "publisher",
"key": "cit0008"
},
{
"DOI": "10.1016/S0140-6736(20)31324-6",
"doi-asserted-by": "publisher",
"key": "cit0009"
},
{
"DOI": "10.1016/j.ejphar.2020.173717",
"doi-asserted-by": "publisher",
"key": "cit0010"
},
{
"key": "#cr-split#-cit0011.1",
"unstructured": "11. Indian Council of Medical Research. Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection. [Internet] 2020. [updated: 2020 May 22"
},
{
"key": "#cr-split#-cit0011.2",
"unstructured": "cited: 2021 March 18]. Available from: https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisory_on_the_use_of_HCQ_SARS_CoV2_infection.pdf"
},
{
"DOI": "10.18203/2320-6012.ijrms20205444",
"doi-asserted-by": "publisher",
"key": "cit0012"
},
{
"DOI": "10.7326/M20-6519",
"doi-asserted-by": "publisher",
"key": "cit0013"
},
{
"DOI": "10.21203/rs.3.rs-72132/v1",
"doi-asserted-by": "publisher",
"key": "cit0014"
},
{
"DOI": "10.1001/jamainternmed.2020.6319",
"doi-asserted-by": "publisher",
"key": "cit0015"
},
{
"DOI": "10.1093/cid/ciaa1571",
"doi-asserted-by": "publisher",
"key": "cit0016"
},
{
"DOI": "10.1056/NEJMc2023617",
"doi-asserted-by": "publisher",
"key": "cit0017"
},
{
"DOI": "10.1056/NEJMoa2021801",
"doi-asserted-by": "crossref",
"key": "cit0018",
"unstructured": "18. Mitjà O, Marc CM, Ubals M et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. N. Engl. J. Med. 2021;384:417–27."
},
{
"key": "cit0019",
"unstructured": "19. World Health Organisation. WHO Coronavirus (COVID-19) Dashboard. [Internet] 2021. [cited: 2021 October 16]. Available from: https://covid19.who.int/"
},
{
"DOI": "10.1016/S1473-3099(21)00344-3",
"doi-asserted-by": "publisher",
"key": "cit0020"
},
{
"DOI": "10.1016/j.jiph.2021.08.001",
"doi-asserted-by": "publisher",
"key": "cit0021"
},
{
"key": "#cr-split#-cit0022.1",
"unstructured": "22. World Health Organisation. Coronavirus disease (COVID-19): Solidarity Trial and hydroxychloroquine. [updated: 2020 June 19"
},
{
"key": "#cr-split#-cit0022.2",
"unstructured": "cited: 2021 October 16]. Available from: https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19-hydroxychloroquine."
},
{
"DOI": "10.1016/j.lana.2021.100062",
"doi-asserted-by": "publisher",
"key": "cit0023"
},
{
"key": "cit0024",
"unstructured": "24. Dinesh B, J CS, Kaur CP et al. Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers - A Multicentric Cohort Study Assessing Effectiveness and Safety. J Assoc Physicians India. 2021;69(6):17-23"
},
{
"key": "#cr-split#-cit0025.1",
"unstructured": "25. World Health Organization. Drugs to prevent COVID-19: A WHO living guideline. [updated: 2021 March 19"
},
{
"key": "#cr-split#-cit0025.2",
"unstructured": "cited: 2021 October 16]. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-prophylaxes-2021-1"
},
{
"DOI": "10.3390/diagnostics11091645",
"doi-asserted-by": "publisher",
"key": "cit0026"
},
{
"DOI": "10.1038/d41586-021-02081-w",
"doi-asserted-by": "publisher",
"key": "cit0027"
},
{
"DOI": "10.1056/NEJMoa2109072",
"doi-asserted-by": "publisher",
"key": "cit0028"
}
],
"reference-count": 31,
"references-count": 31,
"relation": {},
"score": 1,
"short-container-title": [
"Expert Review of Anti-infective Therapy"
],
"short-title": [],
"source": "Crossref",
"subject": [
"Virology",
"Infectious Diseases",
"Microbiology (medical)",
"Microbiology"
],
"subtitle": [],
"title": [
"Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study"
],
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1080/tandf_crossmark_01"
}
