Stella Gagliardi: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy.
Emanuele Tino Poloni: Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Milano, Italy.
Cecilia Pandini: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy.
Maria Garofalo: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
Francesca Dragoni: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
Valentina Medici: Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Milano, Italy.
Annalisa Davin: Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Milano, Italy.
Silvia Damiana Visonà: Department of Public Health, Experimental and Forensic Medicine, Unit of Legal Medicine and Forensic Sciences "A. Fornari", University of Pavia, Pavia, Italy.
Matteo Moretti: Department of Public Health, Experimental and Forensic Medicine, Unit of Legal Medicine and Forensic Sciences "A. Fornari", University of Pavia, Pavia, Italy.
Daisy Sproviero: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy.
Orietta Pansarasa: Genomic and Post Genomic Unit, IRCCS Mondino Foundation, Pavia, Italy.
Antonio Guaita: Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Milano, Italy.
Mauro Ceroni: Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; Department of General Neurology, IRCCS Mondino Foundation, Pavia, Italy.
Livio Tronconi: Department of Public Health, Experimental and Forensic Medicine, Unit of Legal Medicine and Forensic Sciences "A. Fornari", University of Pavia, Pavia, Italy; U.O. Medicina Legale, IRCCS Mondino Foundation, Pavia, Italy.
Cristina Cereda: Director of Newborn Screening and Metabolic Diseases, University Children's Hospital V. Buzzi, Milan, Italy. Electronic address: cristina.cereda@asst-fbf-sacco.it.
SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain.
