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      Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study

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      Travel Medicine and Infectious Disease

      Published by Elsevier Ltd.

      COVID-19, SARS-CoV-2, Hydroxychloroquine, Azithromycin, PCR, Culture

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          We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration.


          We conducted an uncontrolled non-comparative observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU).


          All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days.


          We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.

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          Most cited references 4

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          U.S. outpatient antibiotic prescribing, 2010.

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            Is Open Access

            Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the experience in Sichuan Province, China

            Up to 31 January 2020, there have been 9811 officially reported confirmed cases of 2019-novel coronavirus (nCoV) infection in China since the epidemic began in December 2019 (updated data available at With the rapid transmission, the epidemic has spread throughout the country, and 177 cases have been reported in Sichuan Province. As nCoV infection is a highly contagious disease with high mortality (3–15%) [1–3] and West China Hospital (WCH) is the largest hospital in the southwest of China and the referral medical center in Sichuan Province, it is our responsibility to prepare for admission of additional critically ill patients as a matter of emergency. We have held several expert meetings and have reviewed the related literature to develop a plan to respond to the epidemic [4, 5]. The purpose of the plan is to enable us to provide the maximum level of care to critically ill patients while ensuring the protection of medical staff. Novel coronavirus infection special intensive care team We set up a special emergency multi-disciplinary intensive care team to discuss the problems that we might encounter and countermeasures. Team members include intensive care unit (ICU) physician, infectious disease physician, nurse, respiratory therapist, nosocomial infection control expert, and administrative staff. We first evaluated the isolation conditions and the capacity of our department to admit a larger number of patients. Second, we specified the protection levels for different types of health care activities. Third, we assigned special work such as patient screening, consultation, and transfer to designated staff to minimize the number of health workers who had contact with patients with nCoV infection. Bed and medical equipment preparation WCH is a teaching hospital with 4300 total beds and 8 ICUs of total 206 ICU beds. Under normal conditions, the ICU bed usage is always above 90%. It was not appropriate to treat 2019-nCoV-infected patients in the central area because the large stream of people would have a negative impact on infection control measures to curb the spread of the infection. The hospital authorities decided to vacate 402 beds belonging to the Center of Infectious Disease and the adjacent Fifth Inpatient Building so that both are separated from the rest of the inpatient buildings in WCH (Supplementary Figure 1). Based on the initial data [1, 2] and taking into consideration the surge of critically ill patients, we plan to equip 50 ICU beds initially and adjust on the number of patients, as necessary. We made a list of requirements for other special medical equipment, such as ventilators, bronchoscopes, hemodialysis machines, ultrasound machines, standard personal protective equipment (PPE), and sterilizing equipment. During this epidemic period, a large amount of certified PPE, including medical masks, goggles, face shields, and waterproof isolation gowns, is required. Manufactures of the items on the requirement list were contracted and we drew up an advertisement to the society calling for donations to ensure sufficient supplies. Education and training of staff It is very important to make all staff aware of the public health significance of the epidemic, and of potential challenges in achieving disease control. Strict isolation and protection measures are a top priority. Training content includes hand and respiratory hygiene, use of PPE, safe waste management, environmental cleaning, and sterilization of patient-care equipment [6]. We educate and train staff by means of presentations, short videos, WeChat, and supervision to ensure that staff are following the correct procedures. Protection of medical staff A special access to patients was set up and a boundary between the ward in which the nCoV patients are being treated and the office and living area of medical staff was established. The aim was to minimize the number of medical staff that have contact with a patient at any time, including during daily care, treatment, and transfer; minimize the use of high transmission-risk procedures such as bronchoscopy, manual ventilation, non-invasive ventilation, and tracheotomy. We use airborne precautions if these operations are necessary. Diagnostic imaging procedures such as X-ray and ultrasound at the bedside are prioritized, restricting computed tomography (CT) scans, because they cannot be performed at the bedside. Early case recognition and classification of disease severity A physiological parameter-based warning score is used to facilitate early recognition of patients with severe infection and admission decisions according to the severity classification. The score is a modified version of the National Early Warning Score (NEWS) with age ≥ 65 years added as an independent risk factor based on recent reports [7, 8] (Fig. 1). Fig. 1 Early warning score and rules for 2019-nCoV infected patients. *CCRRT: Critical Care Rapid Response Team Patients are divided into four risk categories based on the score: low, median, high, and exceptional. A specially assigned physician or the special critical care team decides which patients need to be treated in the ICU, taking into consideration the disease severity, opportunity to benefit, and sources of support (Fig. 1). Strict restriction of patient contact All staff are required to report any history of exposure, respiratory symptoms, and temperature before entering the building in which the nCoV patients are treated. Everyone must wear masks, isolation suits, and wash hands if need to be in the building. Family members and non-essential medical staff are strictly forbidden from entering the nCoV ward. Research As nCoV infection is a novel disease, knowledge about it is limited [9, 10], especially regarding the management of critically ill patients. We designed a case report form to collect clinical data, proceed with the ethics committee approval of research protocols, and contact with the laboratory that is qualified to conduct research on highly infectious organisms. In conclusion, the 2019-nCoV epidemic is a threat, not only to China, but also to global health. As ICU physicians, our focus is on the management of the most severe patients. We are unable to predict how many critically ill patients we will receive but are doing the best that we can to be prepared and to work together to overcome the epidemic. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary file1 (JPG 7082 kb)
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              Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot

              Background Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. Method We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. Results Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately three hours of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. Conclusion Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.

                Author and article information

                Travel Med Infect Dis
                Travel Med Infect Dis
                Travel Medicine and Infectious Disease
                Published by Elsevier Ltd.
                11 April 2020
                11 April 2020
                [a ]IHU-Méditerranée Infection, Marseille, France
                [b ]Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France
                [c ]Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France
                [d ]Thai Binh University of Medicine and Pharmacy, Thai Binh, Viet Nam
                [e ]Assistance Publique de Marseille, Hôpital Nord, Explorations Fonctionnelles Respiratories, Aix Marseille Université, France
                [f ]Service de Pharmacie, Hôpital Timone, AP-HM, Marseille, France
                [g ]Laboratoire de Pharmacie Clinique, Aix Marseille Université, Marseille, France
                [h ]Assistance Publique de Marseille, Médecine Interne, Unité de Médecine Aigue Polyvalente (UMAP), France
                [i ]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), France
                [j ]Assistance Publique de Marseille, Hôpital Timone, Cardiologie, Rythomologie, Aix Marseille Université, France
                Author notes
                []Corresponding author. IHU-Méditerranée Infection, Marseille, France. Didier.raoult@

                equal work.

                S1477-8939(20)30131-9 101663
                © 2020 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.


                Infectious disease & Microbiology

                sars-cov-2, covid-19, culture, pcr, azithromycin, hydroxychloroquine


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