Agradecimentos: Prof. Vasco Azevedo for providing the K. pneumonia B31clinical isolate;Prof. Vivian Vasconcelos Costa and Prof. Mauro Martins Teixeira for providing the mouse hepatitis virus MHV-3; Prof. Flaviano S. Martins for providing the probiotic strain B. longum 51A. Daniela M. Nolasco and Prof. Leda Quercia Vieira for technical support; Eduardo Zimmer, Andreza F. de Bem, and Ana Maria Caetano de Faria for valuable discussions. This work was supported by National Council for Scientific and Technological Development - CNPq (call MCTIC/CNPq/FNDCT/MS/SCTIE/Decit 07/2020 [process number: 402530/2020-9], Universal MCTIC/CNPq [process number: 408703/20210]), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) (APQ-03328-18; 642 APQ-00686-21), and Instituto Serrapilheira (Nº 03/2019): A.T.V. Coordenação de Aperfeiçoamento de Pessoal de N??vel Superior, Brazil (CAPES) Finance Code 001: V.M.A and D.A.A. CAPES-Print: I.G. Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais - PRPq: São Paulo Research Foundation (grants 2017/25588-1, 2018/14666-4, 2019/00098-7, 2019/05155-9 and 2020/04746-0): R.S.S. and D.M.S. National Health and Medical Research Council of Australia (105,9238, 1175134, 2010287): P.M.M Ver menos

Abstract: Long-term sequelae after Coronavirus disease (COVID)-19 are frequent and of major concern. SARS-CoV-2 infection affects the host's gut microbiota, which is linked with disease severity in patients with COVID-19. We report here that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with antibiotic-resistance phenotype compared to healthy controls. Additionally, short-chain fatty acids (SCFA) levels were reduced in their feces. Fecal transplant from post-COVID subjects to germ-free mice led to lung inflammation and worst outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. Transplanted mice also had poorer cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection in the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target Ver menos