SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment
Michel Drancourt, Sébastien Cortaredona, Cléa Melenotte, Sophie Amrane, Carole Eldin, Bernard La Scola, Philippe Parola, Matthieu Million, Jean-Christophe Lagier, Didier Raoult, Philippe Colson
Viruses, doi:10.3390/v13050890
SARS-CoV-2 nasopharyngeal shedding contributes to the spread of the COVID-19 epidemic. Among 3271 COVID-19 patients treated at the
This was not our situation, where only one patient had lymphoma and another had immunosuppression following kidney transplantation. In addition, several cases of viral shedding beyond 90 days occurred in patients who received treatments with convalescent plasma and/or remdesivir [17, 18] . These situations were not encountered in this series, as no patient received remdesivir or convalescent plasma and the figures reported here were observed in the context of standardized care, including the prescription of hydroxychloroquine and azithromycin treatment. It is noteworthy that almost one quarter of the 34 persistent shedders reported here did not receive the combination of hydroxychloroquine and azithromycin, a prevalence significantly higher than that in short shedders. This standardized care notably differed in other series reporting a higher proportion of persistent shedders, yet populations may not have been similar, bringing into question the impact of combination of hydroxychloroquine plus azithromycin at the dosage prescribed in reducing the time of SARS-CoV-2 nasopharyngeal shedding. This reported series mirrors the first COVID-19 epidemic in our region, which was caused by SARS-CoV-2 of clades 20A, 20B and 20C. Accordingly, based on next-generation population sequencing we did not observe any genotype pattern in any of the 21 patients whose viral genome could be explored. Further ultradeep sequencing of paired early and late nasopharyngeal swabs in the 34 patients..
References
Amrane, Tissot-Dupont, Doudier, Eldin, Hocquart et al., 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, Travel Med. Infect. Dis,
doi:10.1016/j.tmaid.2020.101632Avanzato, Matson, Seifert, Pryce, Williamson et al., Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer, Cell,
doi:10.1016/j.cell.2020.10.049Aydillo, Gonzalez-Reiche, Aslam, Van De Guchte, Khan et al., Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer, N. Engl. J. Med,
doi:10.1056/NEJMc2031670Baang, Smith, Mirabelli, Valesano, Manthei et al., Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient, J. Infect. Dis,
doi:10.1093/infdis/jiaa666Buckland, Galloway, Nic Fhogartaigh, Meredith, Provine et al., Treatment of COVID-19 with remdesivir in the absence of humoral immunity: A case report, Nat. Commun,
doi:10.1038/s41467-020-19761-2Canarutto, Del Barba, Di Frenna, Del Tedesco, Pajno et al., Prolonged asymptomatic SARS-CoV-2 infection in a child receiving immunosuppressive therapy, Pediatr. Pulmonol,
doi:10.1002/ppul.24983Cevik, Tate, Lloyd, Maraolo, Schafers et al., SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis, Lancet Microbe,
doi:10.1016/S2666-5247(20)30172-5Chen, Zhu, Hong, Zeng, He et al., Associations of clinical characteristics and treatment regimens with the duration of viral RNA shedding in patients with COVID-19, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2020.06.091Choi, Choudhary, Regan, Sparks, Padera et al., Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host, N. Engl. J. Med,
doi:10.1056/NEJMc2031364Colson, Levasseur, Gautret, Fenollar, Hoang et al., Introduction into the Marseille geographical area of a mild SARS-CoV-2 variant originating from sub-Saharan Africa: An investigational study, Travel Med. Infect. Dis,
doi:10.1016/j.tmaid.2021.101980Devine, Maxwell, Haynes, Macbrayne, Boguniewicz, Management of an Immunocompromised Pediatric Patient With Multiple Hospitalizations for Symptomatic COVID-19, J. Pediatr. Hematol,
doi:10.1097/MPH.0000000000002014Fontana, Villamagna, Sikka, Mcgregor, Understanding viral shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2): Review of current literature, Infect. Control Hosp. Epidemiol,
doi:10.1017/ice.2020.1273Fournier, Colson, Levasseur, Gautret, Luciani et al., Genome sequence analysis enabled deciphering the atypical evolution of COVID-19 in
Gautret, Lagier, Parola, Meddeb, Mailhe et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial, Int. J. Antimicrob. Agents,
doi:10.1016/j.ijantimicag.2020.105949Helleberg, Niemann, Moestrup, Kirk, Lebech et al., Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy, J. Infect. Dis
Hensley, Bain, Jacobs, Nambulli, Parikh et al., Intractable Coronavirus Disease 2019 (COVID-19) and Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Replication in a Chimeric Antigen Receptor-Modified T-Cell Therapy Recipient: A Case Study, Clin. Infect. Dis,
doi:10.1093/cid/ciab072Hueso, Pouderoux, Péré, Beaumont, Raillon et al., Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19, Blood,
doi:10.1182/blood.2020008423Jaafar, Aherfi, Wurtz, Grimaldier, Van Hoang et al., Correlation Between 3790 Quantitative Polymerase Chain Reaction-Positives Samples and Positive Cell Cultures, Including 1941 Severe Acute Respiratory Syndrome Coronavirus 2 Isolates, Clin. Infect. Dis,
doi:10.1093/cid/ciaa1491Khatamzas, Rehn, Muenchhoff, Hellmuth, Gaitzsch et al., Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host, medRxiv,
doi:10.1101/2021.01.10.20248871Lagier, Million, Gautret, Colson, Cortaredona et al., Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis, Travel Med. Infect. Dis,
doi:10.1016/j.tmaid.2020.101791Levasseur, Delerce, Caputo, Brechard, Colson et al., Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients, bioRxiv
London, Boutboul, Lacombe, Pirenne, Heym et al., Severe COVID-19 in Patients with B Cell Alymphocytosis and Response to Convalescent Plasma Therapy, J. Clin. Immunol
Malsy, Veletzky, Heide, Hennigs, Gil-Ibanez et al., Sustained Response After Remdesivir and Convalescent Plasma Therapy in a B-Cell-Depleted Patient With Protracted Coronavirus Disease 2019 (COVID-19), Clin. Infect. Dis,
doi:10.1093/cid/ciaa1637Million, Lagier, Gautret, Colson, Fournier et al., Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France, Travel Med. Infect. Dis,
doi:10.1016/j.tmaid.2020.101738Myrstad, Ihle-Hansen, Tveita, Andersen, Nygård et al., National Early Warning Score 2 (NEWS2) on admission predicts severe disease and in-hospital mortality from Covid-19-A prospective cohort study, Scand. J. Trauma Resusc. Emerg. Med,
doi:10.1186/s13049-020-00764-3Nakajima, Ogai, Furukawa, Arai, Anan et al., Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient, J. Infect. Chemother,
doi:10.1016/j.jiac.2020.12.001Pedro, Silva, Magalhães, Cavadas, Rocha et al., Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration, Microorganisms,
doi:10.3390/microorganisms9020300Scola, Le Bideau, Andreani, Hoang, Grimaldier et al., Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards, Eur. J. Clin. Microbiol. Infect. Dis,
doi:10.1007/s10096-020-03913-9Sepulcri, Dentone, Mikulska, Bruzzone, Lai et al., The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient-A case study, MedRxiv,
doi:10.1101/2021.01.23.21249554Tarhini, Recoing, Bridier-Nahmias, Rahi, Lambert et al., Long-Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-2 Superinfection, J. Infect. Dis,
doi:10.1093/infdis/jiab075Tzarnas, Kramer, Alberti, Chan, Alam Khan et al., Convalescent Plasma Therapy in a Refractory Case of COVID-19 in an Immunocompromised Patient, Crit. Care Med,
doi:10.1097/01.ccm.0000726612.71471.ebWei, Liu, Zhao, Chen, Prolonged shedding of SARS-CoV-2 in an elderly liver transplant patient infected by COVID-19: A case report, Ann. Palliat. Med,
doi:10.21037/apm-20-996Widders, Broom, Broom, SARS-CoV-2: The viral shedding vs infectivity dilemma, Infect. Dis. Health
Zheng, Peng, Xu, Zhao, Liu et al., Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis, J. Infect,
doi:10.1016/j.jinf.2020.04.021Zhu, Zhang, Wang, Li, Yang et al., A Novel Coronavirus from Patients with Pneumonia in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2001017
