Cheon IS, Li C, Son YM, et al. Immune signatures underlying post-acute COVID-19 lung sequelae. Sci Immunol. 2021 Sep 30:eabk1741. PubMed: https://pubmed.gov/34591653. Full text: https://doi.org/10.1126/sciimmunol.abk1741
Survivors of severe COVID-19 are at high risk of developing chronic pulmonary sequelae that may be accompanied by abnormal chest imaging and impaired lung function testing. The authors suggest that dysregulated respiratory CD8+ T cell responses might be associated with impaired lung function following acute COVID-19.
Ferren M, Favède V, Decimo D, et al. Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection. Nat Commun 12, 5809 (2021). Full text: https://www.nature.com/articles/s41467-021-26096-z
The authors present organotypic cultures from hamster brainstem and lung tissues that could help to study the early steps of viral infection and screening antivirals.
Ziegler CGK, Miao VN, Owings AH, et al. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. 2021 Jul 23:S0092-8674(21)00882-5. PubMed: https://pubmed.gov/34352228. Full text: https://doi.org/10.1016/j.cell.2021.07.023
After single-cell transcriptome sequencing of nasopharyngeal swabs from 58 people, the authors suggests that failed nasal epithelial anti-viral immunity might underlie and precede severe COVID-19.
Xydakis MS, Albers MW, Holbrook EH, et al. Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021 Jul 30:S1474-4422(21)00182-4. PubMed: https://pubmed.gov/34339626. Full text: https://doi.org/10.1016/S1474-4422(21)00182-4
Why do we lose our smell with COVID-19? And what might be the consequences? The authors postulate that, “in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term.” See also the comment by Doty RL. The mechanisms of smell loss after SARS-CoV-2 infection. Lancet Neurol. 2021 Jul 30:S1474-4422(21)00202-7. PubMed: https://pubmed.gov/34339627. Full text: https://doi.org/10.1016/S1474-4422(21)00202-7
Chen KG, Park K, Spence JR. Studying SARS-CoV-2 infectivity and therapeutic responses with complex organoids. Nat Cell Biol (2021). https://doi.org/10.1038/s41556-021-00721-x
A review of the roles of complex organoids in the study of SARS-CoV-2 infection, modeling of COVID-19 disease pathology and of drug, antibody and vaccine development. The authors anticipate valuable lessons for the study of other viral diseases as well.
Cohen CA, Li APY, Hachim A, et al. SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection. Nat Commun 12, 4678 (2021). Full text: https://doi.org/10.1038/s41467-021-24938-4
Could a reduced prior β coronavirus immunity and reduced T cell activation in children drive a milder COVID-19 pathogenesis? The authors found that infected children have lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults.
Chen S, Yang L, Nilsson-Payant B, et al. SARS-CoV-2 Infected Cardiomyocytes Recruit Monocytes by Secreting CCL2. Res Sq. 2020 Nov 17:rs.3.rs-94634. PubMed: https://pubmed.gov/33236003. Full-text: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00378-7
The study provides evidence that SARS-CoV-2 infects cardiomyocytes in vivo and suggests a mechanism of immune-cell infiltration and histopathology in heart tissues of COVID-19 patients.
Johnson BA, Xie X, Bailey AL, et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature (2021). Full-text: https://doi.org/10.1038/s41586-021-03237-4
The authors generated a mutant SARS-CoV-2 deleting the furin cleavage site (ΔPRRA). SARS-CoV-2 ΔPRRA replicates had faster kinetics, improved fitness in Vero E6 cells, and reduced spike protein processing as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. The findings illustrate the critical role of the furin cleavage site in SARS-CoV-2 infection and pathogenesis. In its absence, the mutant ΔPRRA virus is attenuated in its ability to replicate in certain cell types and cause disease in vivo.
Hann von Weyhern C, Kaufmann I, Neff F. Neuropathology associated with SARS-CoV-2 infection – Authors’ reply. Lancet January 23, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00097-0
Lively Discussion about various hypotheses regarding COVID-19 neuropathology (the authors report a pronounced CNS involvement with pan-encephalitis, meningitis, and brainstem neuronal cell damage in a small case series).
Khamsi R. Rogue antibodies could be driving severe COVID-19. Nature NEWS FEATURE 19 January 2021. Full-text: https://doi.org/10.1038/d41586-021-00149-1
Roxanne Khamsi summarizes the growing evidence that self-attacking ‘autoantibodies’ could be the key to understanding some of the worst cases of SARS-CoV-2 infection.
Cheng XP, Cheng MP, Gu W, et al. Cell-Free DNA Tissues-of-Origin by Methylation Profiling Reveals Significant Cell, Tissue and Organ-Specific injury related to COVID-19 Severity. Cell Med 2021, published 16 January. Full-text: https://www.cell.com/med/fulltext/S2666-6340(21)00031-3
A blood test to broadly quantify cell, tissue, and organ-specific injury due to COVID-19? That’s what Iwijn De Vlaminck and colleagues propose after performing cell-free DNA (cfDNA) profiling on 104 plasma samples from 33 COVID-19 patients. The authors suggest that cfDNA profiling – an easy-to-obtain molecular blood test – might provide quantifiable prognostic parameters and a more granular assessment of clinical severity at the time of presentation.
Grant RA, Morales-Nebreda L, Markov NS, et al. Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature 2021, published 11 January. Full-text: https://doi.org/10.1038/s41586-020-03148-w
SARS-CoV-2 might cause a slowly unfolding, spatially limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation. This is the result of a study that collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling.
Wei C, Wan L, Yan Q, et al. HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nat Metab. 2020 Dec;2(12):1391-1400. PubMed: https://pubmed.gov/33244168. Full-text: https://doi.org/10.1038/s42255-020-00324-0
Could high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitate ACE2-dependent entry of SARS-CoV-2? That is the statement by Hui Zhong, Congwen Wei, finding that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components and facilitates SARS-CoV-2 cellular attachment, entry and infection. SARS-CoV-2 entry is inhibited by silencing SR-B1 expression and by SR-B1 antagonists. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody inhibited HDL-enhanced SARS-CoV-2 infection.
See also the comment by Di Guardo G. SARS-CoV-2-Cholesterol Interaction: A Lot of Food for Thought. Pathogens 2021, 10(1), 32- Full-text: https://doi.org/10.3390/pathogens10010032
Meinhardt J, Radke J, Dittmayer C, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci (2020). Full-text: https://doi.org/10.1038/s41593-020-00758-5
Given the neurological symptoms observed in a large majority of individuals with COVID-19, does SARS-CoV-2 penetrate into the CNS? Here Frank Heppner, Jenny Meinhardt and colleagues demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Watch SARS-CoV-2 crossing the neural–mucosal interface in olfactory mucosa (exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue), following neuroanatomical structures and penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.
See also the comment by Yates D. A CNS gateway for SARS-CoV-2. Nat Rev Neurosci (2021). Full-text: https://doi.org/10.1038/s41583-020-00427-3
Henkel M, Weikert T, Marston K, et al. Lethal COVID-19: Radiological-Pathological Correlation of the Lungs. Radiol Cardiothorac Imaging 2020. Full-text: https://doi.org/10.1148/ryct.2020200406
A report of 14 patients who died from RT-PCR confirmed COVID-19. All patients underwent ante-mortem CT and autopsy. A significant proportion of ground glass opacities (GGO) correlates with the pathologic processes of diffuse alveolar damage, capillary dilatation and congestion and micro-thrombosis. Maurice Henkel, Thomas Weikert and colleagues conclude that these results underline the importance of vascular alterations as a key pathophysiological driver in lethal COVID-19.
Schmidt N, Lareau CA, Keshishian H, et al. The SARS-CoV-2 RNA–protein interactome in infected human cells. Nat Microbiol (2020). Full-text: https://doi.org/10.1038/s41564-020-00846-z
Mathias Munschauer, Nora Schmidt and colleagues provide detailed molecular insights into the identity of host factors and cellular machinery that directly and specifically bind SARS-CoV-2 RNAs during infection of human cells. They integrated CRISPR perturbation data and performed genetic and pharmacological validation experiments that together suggest functional roles for 18 RNA interactome proteins in SARS-CoV-2 infections.
Hernández Cordero AI, Li X, Yang CX, et al. Gene expression network analysis provides potential targets against SARS-CoV-2. Sci Rep 10, 21863 (2020). Full-text: https://doi.org/10.1038/s41598-020-78818-w
Cell entry of SARS-CoV-2 is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Here, the authors show that dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology and might potentially be targetable with existing drugs.
Hennessy EJ, FitzGerald GA. Battle for supremacy: nucleic acid interactions between viruses and cells. J Clin Invest. 2020 Dec 8:144227. PubMed: https://pubmed.gov/33290272. Full-text: https://doi.org/10.1172/JCI144227
The variability in the clinical response to infection with SARS-CoV-2 reflects differences in host genetics and/or immune response. In this review, Elizabeth Hennessy and Garret FitzGerald examine the influence of viruses on the host epigenome and consider how variation in the epigenome may contribute to heterogeneity in the response to SARS-CoV-2.
Simoneau CR, Ott M. Modeling Multi-organ Infection by SARS-CoV-2 Using Stem Cell Technology. Cell Stem Cell 2020, published 3 December. Full-text: https://doi.org/10.1016/j.stem.2020.11.012
OVID-19 is a multi-organ disease causing characteristic complications. In this mini-review, Camille Simoneau and Melanie Ott from the Gladstone Institute of Virology, San Francisco, show that stem cell models of various organ systems—most prominently, lung, gut, heart, and brain—are at the forefront of studies aimed at understanding the role of direct infection in COVID-19 multi-organ dysfunction. A perfect reading for the weekend!