Abstract: viruses Article SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment Michel Drancourt 1,2, *, Sébastien Cortaredona 2,3 , Cléa Melenotte 1 , Sophie Amrane 1,2 , Carole Eldin 2 , Bernard La Scola 1,2 , Philippe Parola 2,3 , Matthieu Million 1,2 , Jean-Christophe Lagier 1,2 , Didier Raoult 1,2 and Philippe Colson 1,2 1 2 3 *



 Citation: Drancourt, M.; Cortaredona, S.; Melenotte, C.; Amrane, S.; Eldin, C.; La Scola, B.; Parola, P.; Million, M.; Lagier, J.-C.; Raoult, D.; et al. SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment. Viruses 2021, 13, 890. https://doi.org/10.3390/v13050890 Academic Editor: Oliver Schildgen Received: 11 March 2021 Accepted: 8 May 2021 Aix Marseille University, IRD, AP-HM, MEPHI, 13005 Marseille, France; clea-leila.melenotte@ap-hm.fr (C.M.); sophie.amrane@ap-hm.fr (S.A.); bernard.la-scola@univ-amu.fr (B.L.S.); matthieu.million@univ-amu.fr (M.M.); jean-christophe.lagier@univ-amu.fr (J.-C.L.); didier.raoult@gmail.com (D.R.); philippe.colson@univ-amu.fr (P.C.) IHU Méditerranée Infection, 13005 Marseille, France; sebastien.cortaredona@univ-amu.fr (S.C.); carole.eldin@ap-hm.fr (C.E.); philippe.parola@univ-amu.fr (P.P.) Aix Marseille University, IRD, SSA, VITROME, 13005 Marseille, France Correspondence: michel.drancourt@univ-amu.fr; Tel.: +33-413-732-401 Abstract: SARS-CoV-2 nasopharyngeal shedding contributes to the spread of the COVID-19 epidemic. Among 3271 COVID-19 patients treated at the Hospital University Institute Méditerranée Infection, Marseille, France from 3 March to 27 April 2020, tested at least twice by qRT-PCR, the median SARS-CoV-2 nasopharyngeal shedding duration was 6 days (range 2–54 days). Compared with short shedders (qRT-PCR positivity < 10 days), 34 (1.04%) persistent shedders (qRT-PCR positivity ≥ 17 days; mean ± SD: 23.3 ± 3.8 days) were significantly older, with associated comorbidities, exhibiting lymphopenia, eosinopenia, increased D-dimer and increased troponin (p < 0.05), and were hospitalized in intensive care unit in 17.7% vs. 1.1% of cases (p < 0.0001). Viral culture was positive in six persistent shedders after day 10, including in one patient after day 17, and no viral co-pathogen was detected in 33 tested patients. Persistent shedders received azithromycin plus hydroxychloroquine ≥ 3 days in 26/34 (76.5%) patients, a figure significantly lower than in short shedders (86.6%) (p = 0.042). Accordingly, mortality was 14.7% vs. 0.5% (p < 0.0001). Persistent shedding was significantly associated with persistent dyspnea and anosmia/ageusia (p < 0.05). In the context of COVID-19 treatment, including treatment with azithromycin plus hydroxychloroquine, the persistence of SARS-CoV-2 nasopharyngeal shedding was a rare event, most frequently encountered in elderly patients with comorbidities and lacking azithromycin plus hydroxychloroquine treatment. Keywords: SARS-CoV-2; COVID-19; viral persistence; culture; qRT-PCR; hydroxychloroquine; azithromycin Published: 12 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/