Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain - 23/03/23

Doi : 10.1016/S1473-3099(22)00794-0

Clara Suñer, PhD ^a,^b,^{*
Joint co-first authors}⁎ , Maria Ubals, MD ^a,^b,^c,^{*
Joint co-first authors}, Eloy José Tarín-Vicente, MD ^c,^d,^{*
Joint co-first authors}, Adrià Mendoza, MD ^a,^b,^e, Andrea Alemany, MD ^a,^b,^c, Águeda Hernández-Rodríguez, PhD ^f,^g, Cristina Casañ, PhD ^f, Vicente Descalzo, MD ⁱ, Dan Ouchi, MSc ^b, Aurélien Marc, MSc ^k, Àngel Rivero, MD ^b,^e, Pep Coll, MD ^b,^e, Xènia Oller, MD ^a,^b, José Miguel Cabrera, MD ^b,^e, Martí Vall-Mayans, PhD ^a,^b, María Dolores Folgueira, PhD ^l,^m,ⁿ, María Ángeles Melendez, PhD ^l,^m, Manuel Agud-Dios, MD ^d, Elena Gil-Cruz, MD ^d, Alexia Paris de Leon, BSc ^f, Aída Ramírez Marinero, MD ^f, Vira Buhiichyk, MD ^b, Cristina Galván-Casas, MD ^b, Roger Paredes, PhD ^b,^o,^v,^w, Nuria Prat, MD ^p, Maria-Rosa Sala Farre, MD ^q, Josep Maria Bonet-Simó, MD ^p, Magí Farré, MD ^r,^u, Pablo L Ortiz-Romero, PhD ^d, Bonaventura Clotet, PhD ^b,^o,^v,^w,^x, Vicente García-Patos, PhD ^j,^s, Jordi Casabona, PhD ^t,^y,^z,^aa, Jeremie Guedj, PhD ^k, Pere-Joan Cardona, PhD ^f,^g,^ab, Ignacio Blanco, PhD ^h,
The Movie Group^{^†}
Collaborator group listed in appendix 2

José Ramón Santos, Lucía Bailón, Susana Benet, Jorge Arroyo Andres, Lorena Calderón Lozano, María Carrasco Díaz, Carla Budria Serrano, Enola Crespillo Galán, Ana Isabel Parra Manzano, Pamela Nef Rabadán, Laura Muntané, Cristina Sánchez-Lafuente Doncel, Yesinei Marina Marrero Pueo, Aroa Muñoz Quinto, Marlon Acosta, Patricia Alvarez, Maider Arando, Jorge N García, Arnau Monforte, Yolanda Maltas Hidalgo, Ramona Hervas Perez, Laura Clotet Romero

Michael Marks, PhD ^ac,^ad,^ae,^{^{‡
Joint senior co-authors}}, Oriol Mitjà, PhD ^a,^b,^w,^af,^{^{‡
Joint senior co-authors}}

^a Skin Neglected Diseases and Sexually Transmitted Infections Section, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

^b Fight Infectious Diseases Foundation, Badalona, Spain

^c Facultat de Medicina, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain

^d Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

^e BCN Checkpoint, Projecte dels NOMS – Hispanosida, Barcelona, Spain

^f Microbiology Department, Clinical Laboratory North Metropolitan Area, University Hospital Germans Trias I Pujol, Badalona, Spain

^g Department of Genetics and Microbiology, Autonomous University of Barcelona, Barcelona, Spain

^h Clinical Genetics Department,Clinical Laboratory North Metropolitan Area, University Hospital Germans Trias I Pujol,Badalona, Spain

ⁱ Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain

^j Department of Dermatology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

^k Université de Paris, INSERM, IAME, F-75018, Paris, France

^l Microbiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

^m Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain

ⁿ Department of Medicine, Medical School, Universidad Complutense de Madrid, Madrid, Spain

^o Infectious Diseases Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

^p Direcció d’Atenció Primària - Metropolitana Nord, Sabadell, Catalonia, Spain

^q Public Health Agency of Catalonia, Generalitat de Catalunya, Barcelona, Spain

^r Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain

^s Facultat de Medicina, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain

^t Department of Paediatrics, Obstetrics and Gynecology and Preventive Medicine, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain

^u Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTP-IGTP), Badalona, Spain

^v IrsiCaixa AIDS Research Institute, Hospital Germans Trias I Pujol, Badalona, Spain

^w Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC), Vic, Spain

^x Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

^y Centre of Epidemiological Studies of HIV/AIDS and STI of Catalonia (CEEISCAT), Health Department, Generalitat de Catalunya, Badalona, Spain

^z Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, Badalona, Spain

^aa CIBER Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain

^ab Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain

^ac Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK

^ad Hospital for Tropical Diseases, London, UK

^ae Division of Infection and Immunity, University College London, London, UK

^af School of Medicine and Health Sciences, University of Papua New Guinea Port Moresby, Papua New Guinea

^* Correspondence to: Dr Clara Suñer, Skin Neglected Diseases and Sexually Transmitted Infections Section, Hospital Universitari Germans Trias i Pujol, Carretera del canyet s/n, 08916, Badalona, Spain Skin Neglected Diseases and Sexually Transmitted Infections Section Hospital Universitari Germans Trias i Pujol Carretera del canyet s/n Badalona 08916 Spain

Summary

Background

Monkeypox DNA has been detected in skin lesions, saliva, oropharynx, urine, semen, and stool of patients infected during the 2022 clade IIb outbreak; however, the viral dynamics within these compartments remain unknown. We aimed to characterise the viral load kinetics over time in various parts of the body.

Methods

This was an observational, prospective, multicentre study of outpatients diagnosed with monkeypox in two hospitals and two sexual health clinics in Spain between June 28, 2022, and Sept 22, 2022. Men and women aged over 18 years were eligible if they reported having symptom onset within the previous 10 days of presentation, and were ineligible if disease was severe enough to be admitted to hospital. Samples were collected from five body locations (skin lesions, oropharynx, rectum, semen or vagina, and a dried blood spot) at six time points up to 57 days after the screening visit. Samples were analysed by quantitative PCR and a subset by cell culture. The primary endpoint was time from symptom onset to viral DNA clearance.

Findings

Overall, 1663 samples were collected from 77 study participants. 75 (97%) participants were men, the median age was 35·0 years (IQR 29·0–46·0), and 39 (51%) participants were living with HIV. The median time from symptom onset to viral clearance was 25 days (95% CI 23–28) in the skin lesions, 16 days (13–19) in the oropharynx, 16 days (13–23) in the rectum, 13 days in semen (9–18), and 1 day in blood (0–5). The time from symptom onset to viral clearance for 90% of cases was 41 days (95% CI 34–47) in skin lesions and 39 days (27–56) in semen. The median viral load in skin lesions was 7·3 log₁₀ copies per mL (IQR 6·5–8·2) at baseline, compared with 4·6 log₁₀ copies per mL (2·9–5·8) in oropharyngeal samples, 5·0 log₁₀ copies per mL (2·9–7·5) in rectal samples, 3·5 log₁₀ copies per mL (2·9–4·7) in semen samples, and 4·0 log₁₀ copies per mL (4·0–4·0) in blood specimens. Replication-competent viruses were isolated in samples with high DNA levels (>6·5 log₁₀ copies per mL).

Interpretation

In immunocompetent patients with mild monkeypox disease, PCR data alone would suggest a contact isolation period of 3 to 6 weeks but, based on detection of replication-competent virus, this time could be reduced. Based on findings from this cohort of patients, semen testing and prolonged use of condoms after recovery from monkeypox might not be necessary.

Funding

University Hospital Germans Trias i Pujol and the YoMeCorono.

Translation

For the Spanish translation of the abstract see Supplementary Materials section.

Le texte complet de cet article est disponible en PDF.

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Vol 23 - N° 4

P. 445-453 - avril 2023 Retour au numéro

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Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain - 23/03/23

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