Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19
Mazzitelli et al.
, Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident..
, Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826
Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified.
Mazzitelli et al., 31 Jul 2020, peer-reviewed, 8 authors.
Abstract: Travel Medicine and Infectious Disease 37 (2020) 101826
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Travel Medicine and Infectious Disease
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Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance
in an incident cohort of geriatric patients with COVID-19
To the Editor:
Gautret at al. published results of non-randomized studies suggesting
efficacy of hydroxychloroquine and azithromycin (HCQ/AZI) in patients
with COVID-19 [1,2]. Particularly, among 80 mildly infected patients,
83% at day 7 and 93% at day 8 achieved negative results of RT-PCR for
SARS-CoV-2 from nasopharyngeal swabs . More recently, data from a
multicenter study of 1061 patients were published, showing that all but
one patient were PCR-cleared at day 15 .
Following the extraordinary success rate of the first study , we
started prescribing HCQ/AZI in our patients, so from March 28th to
April 4th, 2020, 41 patients took HCQ (200 mg thrice daily) and AZI 500
mg for the first day and 250 mg for the subsequent 4 days. All patients
got infected from a unique outbreak in a long-term facility, with the date
of infection estimated around a week before admission. So, in this study
on an incident cohort, we minimized the risk of interpreting a rapid PCR
clearance as an effect of the prescribed treatment, while such clearance
may be simply spontaneous in patients infected for a longer time.
Among 41 patients, ten died for severe COVID-19 (6 patients took
treatment for ≤2 days, and 4 for <5 days), and one refused to be retested
for SARS-CoV-2. So, 30 patients were evaluated after completion of the
treatment course. Among them, 17 (51%) were females; median age was
83 years (IQR: 65–88). Recorded comorbidities were: hypertension
(76.6%), neurological diseases (43.3%), chronic kidney disease (43.3%),
and psychiatric disorders (33.3%). Nine (30%) patients were diagnosed
with COVID-19 pneumonia (three requiring oxygen support). Twelve
patients had upper respiratory symptoms. Five patients had respiratory
failure without radiological evidence of pneumonia. Four patients were
asymptomatic. Real time reverse transcriptase–polymerase chain reac
tion (RT-PCR) to detect SARS-CoV-2 genome on nasopharyngeal swabs
was performed with Gene Finder TM COVID-19 Plus RealAmp Kit,
ELITech Group, Puteaux, France.
After one week from starting treatment, only 3 (10%) patients re
ported negative results on nasopharyngeal swabs. All the other patients
remained positive also at the following swab after one week. Twentynine patients survived and became asymptomatic, but one 84 year-old
man remained positive and died three weeks after treatment.
In conclusion HCQ in combination with AZI did not show an effect
comparable to that obtained in other studies [1–3]. Clearly, patient
characteristics (age, comorbidities, more severe diseases) may have
played a role in reducing the rate of virological response. However, since
in our incident cohort patients were treated soon after the putative date
of infection, the apparent discrepancy may also be due to selection of
patients who needed more time to reach spontaneous clearance, while
those treated by Gautret at al . may have received HCQ and AZI closer
to the moment when natural clearance of SARS-CoV-2 would have
occurred anyway. This indicated both the importance of a careful
Received 14 May 2020; Accepted 27 July..
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