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L’objectiu d’aquest estudi va ser evidenciar diferències, pel que fa a la càpsula fibrosa, entre els granulomes petits d’animals vacunats amb BCG (posteriorment inoculats amb M.caprae) i d’animals control (també inoculats amb M.caprae) mitjançant la tinció tricròmica de Masson, que permetessin explicar l’evolució diferent de la lesió tuberculosa en cada grup. Es van utilitzar 12 animals, 6 vacunats i 6 no vacunats (controls), en la infecció experimental, i a partir d’aquests es van obtenir els talls histològics de parènquima pulmonar, per a l’avaluació de la càpsula dels granulomes tuberculosos (o tubercles). Per a la realització d’aquesta es van tenyir els talls amb la tinció de Masson i es va avaluar qualitativament la presència de càpsula i la localització dels granulomes i semiquantitativament el gruix de la càpsula i la presència d’estroma, dividint els granulomes en dos grups en funció de la seva mida: de menys d’1 mm de diàmetre i d’1 a 5mm de diàmetre. Es va observar major grau de no encapsulament en granulomes d’animals no vacunats que en vacunats, tant en granulomes de menys d’1 mm de diàmetre com en granulomes d’1 a 5mm de diàmetre. A nivell individual es va observar que hi havia 3 dels 6 animals control que no estaven encapsulant la majoria dels granulomes d’entre 1 i 5mm de diàmetre, mentre que en el grup de vacunats només hi havia un animal poc encapsulador. Pel que fa a gruix de càpsula, es va observar un fenomen semblant, amb els animals vacunats encapsulant amb més capes els seus granulomes que els controls. Quant a la presència d’estroma, es va observar que els animals BCG en tenien més en els granulomes petits (

The pandemic spread of SARS-CoV-2, the etiological agent of COVID-19, represents a significant and ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection and inflammation that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 tropism and replication. Utilizing a 3D air-liquid interface (ALI) model that closely mimics the natural tissue physiology and cellular tropism of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. We show that temperature elevation induces wide-spread transcriptome changes that impact upon the regulation of multiple pathways, including epigenetic regulation and lncRNA expression, without disruption of general cellular transcription or the induction of interferon (IFN)-mediated antiviral immune defences. Respiratory tissue incubated at temperatures >37°C remained permissive to SARS-CoV-2 infection but severely restricted the initiation of viral transcription, leading to significantly reduced levels of intraepithelial viral RNA accumulation and apical shedding of infectious virus. To our knowledge, we present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication. Our data identify an important role for temperature elevation in the epithelial restriction of SARS-CoV-2 that occurs independently of the induction of canonical IFN-mediated antiviral immune defences and interferon-stimulated gene (ISG) expression.

The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air–liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses., A clinical feature of COVID-19 is the onset of fever, raising the body temperature to 38-41°C. This study demonstrates that temperature elevation to 40°C limits the replication of SARS-CoV-2 in respiratory airway cultures, independently of the induction of interferon-mediated antiviral immune defences.

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