Raoult’s Hydroxychloroquine-Azithromycin Cure For Covid: 80 Patient Study

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study
Running title: Hydroxychloroquine-Azithromycin and COVID-19

Long story short:

The light beige line denotes the patients who are contagious (shedding virus). Basically, none of the 80 patients shed virus after ten days. The median virus shedding time is 20 days (Chinese studies). Quinine-Azithromycin works!

[Authors [1]]
Abstract:
We need an effective treatment to cure COVID-19 patients and to decrease the virus carriage duration. In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin. We noted a clinical improvement in all but one 86 year-old patient who died, and one 74 year old patient still in intensive care unit. A rapid fall of nasopharyngeal viral load tested by qPCR was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% patients at Day5. This allowed patients to rapidly be discharged from highly contagious wards with a mean length of stay of five days. We believe other teams should urgently evaluate this cost-effective therapeutic strategy, to both avoid the spread of the disease and treat patients as soon as possible before severe respiratory irreversible complications take hold.
Keywords: COVID-19; SARS-CoV-2; hydroxychloroquine; azithromycin; PCR; culture.
Introduction:
In late December 2019, an outbreak of an emerging disease (COVID-19) due to a novel coronavirus (named SARS-CoV-2 latter) began in Wuhan, China and quickly spread in a substantial number of countries (1;2). The epidemic was declared a pandemic by the WHO on 12 March 2020 (3). According to a Chinese study, 80% of patients present with mild symptoms and the overall fatality rate is about 2.3%, although this rises to 8.0% in patients between the ages of 70 to 79 years and to 14.8% in those aged 80 years and over (4).
However, it is highly likely that there are a significant number of asymptomatic carriers in the population, and thus it is probable that the mortality rate has been overestimated. To take the example of the outbreak onboard the Diamond Princess cruise-ship, the fatality rate was 1.4%
(5). France is now facing the onslaught of COVID-19 with more than 25,000 cases, as March 26th, 2020 (5). Thus, there is a critical and urgent need for an effective treatment in order to cure symptomatic patients but also to decrease the duration of virus carriage and thus limit transmission in the community. Among the candidate drugs to treat COVID-19, repositioning
old drugs for use as an antiviral treatment is an interesting strategy, because knowledge about these drugs’ safety profile, side effects, posology and drug interactions are already well known (6;7).
Three in vitro studies have demonstrated that chloroquine phosphate inhibits SARS-CoV-2 (8;9) and two have demonstrated that hydroxychloroquine sulfate inhibits SARS-CoV-2 (8-10). Other studies have pointed out that drug repurposing may identify approved drugs that could be useful for the treatment of this disease including, notably, chloroquine,
hydroxychloroquine and azithromycin, as well as anti-diabetics such as metformin, angiotensin receptor inhibitors such as sartans, or statins such as simvastatin (11). In addition, chloroquine has demonstrated its efficacy in Chinese COVID-19 patients in clinical trials by reducing fever, improving CT imaging, and delaying disease progression (12-14), leading Chinese experts to recommend chloroquine-based treatment (500 mg twice per day for ten days) as a first line-treatment for mild, moderate and severe cases of COVID-19 (15).
In a preliminary clinical trial on a small cohort of COVID-19 patients, we demonstrated that those treated with hydroxychloroquine (600 mg per day, N=20 patients) had a significant reduction in viral carriage at D6-post inclusion, with 70% of patients testing negative for the virus through nasopharyngeal PCR, compared to untreated controls (N=16) with only 12.5% patients testing negative using PCR at D6-post inclusion (16). In addition, of the twenty patients who were treated with hydroxychloroquine, six received azithromycin for five days (for the purposes of preventing bacterial super-infection) and all (100%) were virologically cured at D6-post inclusion, compared to 57.1% of the remaining 14 patients (16). By contrast,
a Chinese study conducted in 30 COVID-19 patients showed no significant differences between patients treated with 400 mg per day during five days (N=15) and controls (N=15)
regarding pharyngeal carriage of viral RNA at day7, however, patients received multiple
additional treatments including antivirals (17).
A recent Chinese survey revealed that the median duration of viral shedding was 20.0 days (IQR 17.0–24.0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.
The shortest observed duration of viral shedding among survivors was eight days, whereas the longest was 37 days (18). Therefore, a treatment enabling the viral carriage to be cleared and COVID-patients to be clinically cured at an early stage would help limit the transmission of the virus.
In this report we describe our results in patients treated with hydroxychloroquine in combination with azithromycin over a period of at least three days, with three main endpoints:
i) clinical outcome ii) contagiousness as assessed by PCR and culture and iii) long of stay in infectious disease (ID) unit.
Methods:
The study was conducted at the University Hospital Institute Méditerranée Infection in
Marseille, France. Patients with PCR-documented SARS-CoV-2 RNA from a nasopharyngeal sample were admitted to our infectious diseases (ID) ward. It should be noted that six patients enrolled at our institute who were described in our first paper, with a six-day follow-up (N=6) (16), were also included in the present study, with a longer follow-up.
Clinical classification and clinical follow-up: 
Upon admission, patients were grouped into two categories: i) those with an upper respiratory tract infection (URTI) presenting with rhinitis and/or pharyngitis, and/or isolated low-grade fever and myalgia, and ii) those with lower respiratory tract infections (LRTI) presenting with symptoms of pneumonia or bronchitis. The time between the onset of symptoms and admission, and the time between the onset of symptoms and treatment was documented. Risk factors for severe COVID-19, including older age, cancer, cardiovascular disease, hypertension, and diabetes (4), as well as chronic obstructive pulmonary disease, obesity and
any immunosuppressive treatments were documented.

PA

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Authors: Philippe Gautret1,2,£, Jean-Christophe Lagier1,3,$, Philippe Parola1,2, Van Thuan Hoang1,2,4, Line Meddeb1, Jacques Sevestre1, Morgane Mailhe1, Barbara Doudier1, Camille Aubry1, Sophie Amrane1, Piseth Seng1, Marie Hocquart1, Julie Finance5, Vera Esteves Vieira1, Hervé Tissot Dupont1,3, Stéphane Honoré6,7, Andreas Stein1,3, Matthieu Million1,3, Philippe
Colson1,3, Bernard La Scola1,3, Véronique Veit8, Alexis Jacquier9, Jean-Claude Deharo10, Michel Drancourt1,3, Pierre Edouard Fournier1,2, Jean-Marc Rolain1,3, Philippe Brouqui1,3 Didier Raoult1,3* IHU-Méditerranée Infection, Marseille, France.
2Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France. 3Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France. 4Thai Binh University of Medicine and Pharmacy, Thai Binh, Viet Nam 5Assistance Publique de Marseille, Hôpital Nord, Explorations Fonctionnelles Respiratoires, Aix Marseille Université. 6 Service de Pharmacie, Hôpital Timone, AP-HM, Marseille, France. 7 Laboratoire de Pharmacie Clinique, Aix Marseille Université, Marseille, France 8 Assistance Publique de Marseille, Médecine Interne, Unité de Médecine Aigue Polyvalente (UMAP).
9 Department of Radiology and Cardiovascular Imaging, Aix-Marseille Université, UMR 7339, CNRS, CRMBM-CEMEREM (Centre de Résonance Magnétique Biologique et Médicale-Centre d’Exploration Métaboliques par Résonance Magnétique)
10 Assistance Publique de Marseille, Hôpital Timone, Cardiologie, Rythomologie, Aix-Marseille Université.
*Corresponding author: Didier Raoult. Didier.raoult@gmail.com

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P/S: The Raoult paper lists contraindications. Mostly people known to have problems with quinine and AZT…

Tags: 80 patients, Quinine-Azithromycin, Raoult