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The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome_App/ ) to enrich and expand this knowledgebase., (© 2024. The Author(s).)

Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae . transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on 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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4 + T helper cells, but not CD8 + T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients., Competing Interests: NB, GD, Dd, AF, GS, SM, TK, VB, LM, JV, GP, NW, LN, VC, AD, FV, LT, JF, IC, LS, AP, EM, RU, AB, TN, LR, MA, MM, LB, FC, RL, JG, NM, AM, RS, MA, DT, PP, MM, KB, CS, FG, VS, Ed, VF, MC, BC, AP, LC, MD, PR, AG, FP, LS, LB, SS, MP, SW, AS, RC, AV, MV, AD, LV, AF, Ld, TC, HN, HM, RM, DM, MS, JP, PM, MM, AF No competing interests declared, (© 2023, Brunetti, Davanzo, de Moraes et al.)

COVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment., (© 2022 International Society for Neurochemistry.)

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion., (© 2022. The Author(s).)

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.