Sir,
We thank Lacout et al. [1] for their letter about our work on the effect of hydroxychloroquine (HCQ) and azithromycin (AZI) combination against COVID-19 (coronavirus disease 2019) in elderly nursing home residents [2]. They discuss reasons for the contradictory results obtained by Magagnoli et al. in US veterans [3], suggesting that the explanation may be that these authors administered combined treatment at an advanced stage of the disease when patients were hospitalised, while in our study patients were treated earlier, mostly following mass screening for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at nursing homes. Indeed, the mean time between virological diagnosis and treatment was 2.5 ± 3.0 days in our study. In addition, in the US study the proportion of patients with low lymphocyte count (a well-known severity marker in COVID-19 patients) was significantly higher in those allocated to HCQ + AZI combined treatment (30%) compared with controls (19%), which suggests that treated patients were more severe at enrolment.
Recently, another study conducted on COVID-19 patients at a nursing home in the Principality of Andorra was published [4]. These authors reported that combined treatment with HCQ + AZI was independently associated with a significant reduction in mortality rate compared with β-lactam, quinolone or no treatment (odds ratio = 0.044; P = 0.004), which corroborates our results. Interestingly, 56% patients received the combined treatment within 24 h of symptom onset. Details of the three studies are presented in Table 1 .
Table 1.
Details of three retrospective studies addressing the effect of hydroxychloroquine and azithromycin (HCQ+AZT) combination against COVID-19 in elderly people
| Study | Setting | Age (years), % male a | Source of information | Total COVID-19 cases | HCQ+AZT [N (lethality rate)] | Controls [N (lethality rate)] |
|---|---|---|---|---|---|---|
| Study 1 [3] | Veterans Health Administration medical centres across the USA | 71 (median), 96% | Administrative codes | 807 | 214 (23%) | 395 (9%) |
| Study 2 [2] | Nursing homes, Marseille, France | 85 (median), 40% | Medical charts | 226 | 116 (15%) | 110 (26%) |
| Study 3 [4] | Nursing home, Andorra | 86 (mean), 42% | Medical charts | 100 | 80 (10%) | 21 (62%) |
COVID-19, coronavirus disease 2019.
Age and male proportion in patients treated with HCQ+AZT and controls.
In both the French and Andorran studies there was relative homogeneity of care practice, while in the US study conducted in medical centres across the country greater heterogeneity was very likely. In addition, the former studies were based on medical chart retrospective review, whereas the US study was conducted using codes to identify clinical characteristics and study outcomes, which is much less accurate [5].
In conclusion, interpretation of retrospective data addressing the effect of treatments for COVID-19 should be interpreted with caution, notably when a treatment may be more effective at a given stage of the disease. Multicentre retrospective studies, where disease severity is assessed on coded data with little or no information about the timing of therapy, may lead to incorrect interpretation.
Acknowledgments
Funding
None.
Competing interests
None declared.
Ethical approval
Not required.
Editor: Dr Jim Gray
References
- 1.Lacout A, Lounas V, Perronne C. Timing and dosage may be the key in the realization of hydroxychloroquine + azithromycin treatment benefit in Covid-19 elderly patients. Int J Antimicrobial Agents 2021 [Epub ahead of print]. [DOI] [PMC free article] [PubMed]
- 2.Ly T.D.A., Zanini D., Laforge V., Arlotto S., Gentile S., Mendizabal H. Pattern of SARS-CoV-2 infection among dependant elderly residents living in long-term care facilities in Marseille, France, March–June 2020. Int J Antimicrob Agents. 2020;56 doi: 10.1016/j.ijantimicag.2020.106219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Magagnoli J., Narendran S., Pereira F., Cummings T.H., Hardin J.W., Sutton S.S. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19. Med (N Y) 2020;1:114–127. doi: 10.1016/j.medj.2020.06.001. e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Heras E., Garibaldi P., Boix M., Valero O., Castillo J., Curbelo Y. COVID-19 mortality risk factors in older people in a long-term care center. Eur Geriatr Med. 2020 Nov 27 doi: 10.1007/s41999-020-00432-w. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ioannidis J.P. Why most published research findings are false. PLoS Med. 2005;2:e124. doi: 10.1371/journal.pmed.0020124. [DOI] [PMC free article] [PubMed] [Google Scholar]