om as , F e r na n d o G on zález Candelas, SeqCOVID-SPAIN consortium, Tanja Stadler & Richard A. NeherThis is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions ( R e < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Background Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. Materials/methods In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection within a minimal follow-up of 12 months. We used Fisher’s exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. Results We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was two-stage exchange in 95 (50.8%), one-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%). Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted HR=2.15, p=0.03) and antibiotic treatment over 6 weeks (adjusted HR=0.29, p=0.0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment – though not statistically significant for treatment failure (adjusted HR=0.5, p=0.07) and not for relapses (adjusted HR=0.5, p=0.10). Conclusions We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI but a dedicated prospective multicenter study is needed.

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Introducción: La povidona yodada y el peróxido de hidrógeno podrían ser eficaces contra el SARS-CoV-2. Métodos: Estudio observacional de seguimiento prospectivo (EPA-AS) en 88 pacientes (43±17 años, 55% varones) con SARS-CoV-2 en muestras nasofaríngeas (RT-PCR). 31 recibieron enjuagues/gargarismos con povidona yodada cada 8 horas dos días consecutivos, 17 con la misma pauta de peróxido de hidrógeno, y 40 controles sin enjuagues. Se repitió PCR a 3, 11 y 17 días. Resultados: Tras la intervención no hubo diferencias en la carga viral: povidona yodada (4,3±2,7 copias/ml), peróxido de hidrógeno (4,6±2,9 copias/ml; p=0,40), controles (4,4±3,0 copias/ml). El porcentaje de pacientes con 2ª PCR negativa fue 27% povidona yodada, 23% peróxido de hidrógeno y 32% controles; en la 3ª PCR 62%, 54% y 58% respectivamente y en la 4ª PCR, 81%, 75% y 81%. Conclusión: Nuestros resultados no apoyan la utilidad de los enjuagues de estos dos antisépticos en pacientes con COVID-19.