COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Delorey, Toni; Ziegler, Carly G.K.; Heimberg, Graham; Normand, Rachelly; Yang, Yiming; Segerstolpe, Åsa; Abbondanza, Domenic; Fleming, Stephen J.; Subramanian, Ayshwarya; Montoro, Daniel T.; Jagadeesh, Karthik A.; Dey, Kushal Kumar; Sen, Pritha; Slyper, Michal; Pita-Juárez, Yered; Phillips, Devan; Biermann, Jana; Bloom-Ackermann, Zohar; Barkas, Nikolaos; Ganna, Andrea; Gómez, James; Melms, Johannes C.; Katsyv, Igor; Normandin, Erica; Yeganeh, Pourya Naderi; Popov, Yury; Raju, Siddharth S.; Niezen, Sebastian; Tsai, Linus; Siddle, Katherine J.; Sud, Malika; Tran, Victoria M.; Vellarikkal, Shamsudheen Karuthedath; Wang, Yiping; Amir-Zilberstein, Liat; Atri, Deepak; Beechem, Joseph M.; Brook, Olga R.; Chen, Jonathan; Divakar, Prajan; Dorceus, Phylicia; Engreitz, J; Essene, Adam L.; Fitzgerald, Donna M.; Fropf, Robin; Gazal, Steven; Gould, Joshua; Grzyb, John; Harvey, Tyler; Hecht, Jonathan L.; Hether, Tyler; Jané‐Valbuena, Judit; Leney-Greene, Michael; Ma, Hui; McCabe, Cristin; McLoughlin, Daniel E.; Miller, Eric; Muus, Christoph; Niemi, Mari; Padera, Robert F.; Pan, Liuliu; Pant, Deepti; Pe’er, Carmel; Pfiffner-Borges, Jenna; Pinto, Christopher J.; Plaisted, Jacob; Reeves, Jason; Ross, Marty; Rudy, Melissa; Rueckert, Erroll H.; Siciliano, Michelle; Sturm, Alexander; Todres, Ellen; Waghray, Avinash; Warren, Sarah; Zhang, Shuting; Zollinger, Daniel R.; Cosimi, Lisa A.; Gupta, Rajat M.; Hacohen, Nir; Hibshoosh, Hanina; Hide, Winston; Price, Alkes L.; Rajagopal, Jayaraj; Tata, Purushothama Rao; Riedel, Stefan; Szabó, Gyöngyi; Tickle, Timothy L.; Ellinor, Patrick T.; Hung, Deborah T.; Sabeti, Pardis C.; Novak, Richard M.; Rogers, Robert; Ingber, Donald E.; Jiang, Zhihua; Juric, Dejan; Babadi, Mehrtash; Farhi, Samouil L.; Izar, Benjamin; Stone, James R.; Vlachos, Ioannis S.; Solomon, Isaac H.; Ashenberg, Orr; Porter, Caroline; Li, Bo; Shalek, Alex K.; Villani, Alexandra‐Chloé; Rozenblatt-Rosen, Orit; Regev, Aviv

doi:10.1038/s41586-021-03570-8

Cited by 561 publications

(602 citation statements)

References 60 publications

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“…Investigations of SARS-CoV-2 organotropism, its duration in the target organs and the correlation with disease progression are pivotal for developing effective strategies for the containment of the pandemic. Some studies revealed SARS-CoV-2 distribution in human tissues and viral shedding in body fluids, 18,[35][36][37][38] but the translational significance remains unclear. Our pathological evidence of SARS-CoV-2 presence in late stage of critically ill patients with COVID-19 suggests that continued usage of antiviral therapy is indispensable throughout the disease course.…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that definitive detection of SARS-CoV-2 spike or nucleocapsid protein by immunohistochemical (IHC) staining should confirm in situ viral presence in the lungs and extrapulmonary organs, thereby establishing direct evidence of viral infection of target organs. [16][17][18][19] In this study, we profiled SARS-CoV-2 organotropism using 26 autopsy cases from four cohorts in Wuhan, China, and evaluated virus-associated organ injuries. We classified COVID-19 into two pathological subtypes as intrapulmonary infection and systemic infection respectively.…”

Section: Introductionmentioning

confidence: 99%

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A cohort autopsy study defines COVID-19 systemic pathogenesis

et al. 2021

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Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood–air barrier, blood–testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A cohort autopsy study defines COVID-19 systemic pathogenesis

et al. 2021

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“…[1][2][3][4] Moreover, the tolerance of these patients to physical activity and quality of life in general decreases sharply. 5 Again, the risk of long-term physical, cognitive, and emotional complications, the so-called PICS syndrome (Post Intensive Care Syndrome, Post-Reanimation Syndrome), increases in severe and critical patients who stay in intensive care units (ICU) for a long time. 6 Major risk factors include cognitive impairment, acute brain dysfunction, hypoxia, and arterial hypotension.…”

mentioning

confidence: 99%

Telemedicine platform COVIDREHAB for remote rehabilitation of patients after COVID-19

et al. 2021

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The world's practice has shown the importance of medical rehabilitation, which allows increasing the effectiveness of treatment of patients with COVID-19, and also significantly reduce the risks of developing complications after COVID-19. Moreover, timely medical rehabilitation reduces the frequency of disability retirement. We developed and investigated the effectiveness of the telemedicine platform “COVIDREHAB” in order to enhance the effectiveness of the recovery period during self-isolation, as well as to provide access to rehabilitation for patients residing in remote areas or unable to undergo in-person medical rehabilitation. This pilot open clinical study includes 178 patients (108 women and 70 men) aged 32 to 82 years [mean age 50 (33-56) years] who had a moderate disease of COVID-19. We used the specialised platform COVIDREHAB for remote monitoring of the rehabilitation efficiency of patients who suffered from COVID-19. During the study, the supervising doctor assigned the patient a set of specialised questionnaires, which were filled in online. The questionnaires distributed to the patient included questions specifically designed for the COVIDREHAB remote platform as well as the mMRC (Modified Medical Research Council) questionnaire. Patients who completed the remote rehabilitation programme were found to have positive dynamics of indicators of the respiratory system functional state, and complaints.Pulmonary rehabilitation is an important part of case management for patients with respiratory diseases and plays an active role in improving lung function and general well-being of patients. Patients who completed the comprehensive medical rehabilitation program using the information and analytical system COVIDREHAB, were found to have positive dynamics of indicators of the respiratory system functional state, and complaints. Hence, at the end of the course the shortness of breath severity decreased (from 34.8% to 12.4%, as well as the feeling of lack of oxygen from 32% to 17.4%, p <0.05). We anticipate the online approach to rehabilitation will improve the functioning of the respiratory and cardiovascular systems, restore physical function, reduce anxiety and depression, and restore quality of life. An essential benefit of this program is the prevention of secondary complications and reduction of serious adverse effects of COVID-19 treatment."

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“…Similar to HIV-1, SARS-CoV-2 profoundly interacts and modifies the cellular physiology both on the transcriptional [169][170][171][172][173] and protein levels [128,170,174,175]. Host responses to SARS-CoV-2 vary substantially depending on viral load, infection stage, disease severity, body tissue, and cell type as well as age and sex of the host [172,176,177]. Coupled to the induction of an antiviral response, the expression of the SARS-CoV-2 receptor and interferon-responsive gene ACE2 is upregulated by the infected host cell in a viral load-dependent manner.…”

Section: Virus-host Interaction and Exploitation Of The Cellular Machinerymentioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Cited by 561 publications

References 60 publications

A cohort autopsy study defines COVID-19 systemic pathogenesis

A cohort autopsy study defines COVID-19 systemic pathogenesis

Telemedicine platform COVIDREHAB for remote rehabilitation of patients after COVID-19

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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