Materiały źródłowe

• #1 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] Coronaviruses are known to exert their effects by cytocidal and immune-mediated mechanisms. In vitro studies using cell culture assays have shown that coronavirus infection commonly results in cytopathic effects such as cellular lysis or apoptosis. […] Also, immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] The most obvious gene which is likely to be a key modifier of SARS pathomechanisms is the spike (S) protein gene.

• #2

  https://link.springer.com/article/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] SARS-CoV has been shown to cause cytopathic effects in Vero cells and the formation of syncytia in lung tissues. A further similarity with other coronaviruses seems to be the potential of the SARS-CoV to cause tissue fibrosis. […] Next to cytocidal effects, also immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] It is therefore crucial that these immune mechanisms are further analysed on the molecular level as it seems appropriate that not only antiviral but also anti-inflammatory strategies are evaluated for a use in the clinical management of future SARS cases.

• #3 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARSCoV. […] The pathogenesis of SARSCoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARSCoV. […] Studies of the tissue and cellular distribution of SARSCoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. […] ACE2 is expressed at high level in the primary target cells of SARSCoV, namely pneumocytes and surface enterocytes of the small intestine. […] Despite the fact that SARSCoV can infect the lung and intestine, the tissue responses in these two organs are different. […] All other tissues and cell types expressing ACE2 may be potential targets of SARSCoV infection.

• #4 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARSCoV. […] The pathogenesis of SARSCoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARSCoV. […] Studies of the tissue and cellular distribution of SARSCoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. […] ACE2 is expressed at high level in the primary target cells of SARSCoV, namely pneumocytes and surface enterocytes of the small intestine. […] Despite the fact that SARSCoV can infect the lung and intestine, the tissue responses in these two organs are different. […] All other tissues and cell types expressing ACE2 may be potential targets of SARSCoV infection.

• #5 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARSCoV. […] The pathogenesis of SARSCoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARSCoV. […] Studies of the tissue and cellular distribution of SARSCoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. […] ACE2 is expressed at high level in the primary target cells of SARSCoV, namely pneumocytes and surface enterocytes of the small intestine. […] Despite the fact that SARSCoV can infect the lung and intestine, the tissue responses in these two organs are different. […] All other tissues and cell types expressing ACE2 may be potential targets of SARSCoV infection.

• #6 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARSCoV. […] The pathogenesis of SARSCoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARSCoV. […] Studies of the tissue and cellular distribution of SARSCoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. […] ACE2 is expressed at high level in the primary target cells of SARSCoV, namely pneumocytes and surface enterocytes of the small intestine. […] Despite the fact that SARSCoV can infect the lung and intestine, the tissue responses in these two organs are different. […] All other tissues and cell types expressing ACE2 may be potential targets of SARSCoV infection.

• #7 Immunopathogenesis of severe acute respiratory syndrome coronavirus-2: evolving knowledge and its current status

  https://www.explorationpub.com/Journals/ei/Article/10037

  The three severe acute respiratory syndrome (SARS) viruses discovered, including the SARS-CoV-2, share the same mechanism of pathogenesis, although they differ in entry receptor, they use to gain access to the host cell. […] The host cell entry of both SARS-CoV and SARS-CoV-2 virus is mediated via angiotensin-converting enzyme (ACE) 2 receptor-mediated endocytosis, followed by uncoating, and the RNA genome release into the cytoplasm. […] The binding of S protein to ACE2 results in down-regulation, and this is thought to be the primary cause leading to lung injury. […] The pneumocytes and enterocytes are the primary target cells as they express a copious amount of ACE2-through which they enter the host cell. […] Severe SARS-CoV-2 infection is typified by viral pneumonia, which culminates into acute respiratory distress syndrome (ARDS).

• #8 Immunopathogenesis of severe acute respiratory syndrome coronavirus-2: evolving knowledge and its current status

  https://www.explorationpub.com/Journals/ei/Article/10037

  The three severe acute respiratory syndrome (SARS) viruses discovered, including the SARS-CoV-2, share the same mechanism of pathogenesis, although they differ in entry receptor, they use to gain access to the host cell. […] The host cell entry of both SARS-CoV and SARS-CoV-2 virus is mediated via angiotensin-converting enzyme (ACE) 2 receptor-mediated endocytosis, followed by uncoating, and the RNA genome release into the cytoplasm. […] The binding of S protein to ACE2 results in down-regulation, and this is thought to be the primary cause leading to lung injury. […] The pneumocytes and enterocytes are the primary target cells as they express a copious amount of ACE2-through which they enter the host cell. […] Severe SARS-CoV-2 infection is typified by viral pneumonia, which culminates into acute respiratory distress syndrome (ARDS).

• #9 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) – anatomic pathology perspective on current knowledge | Diagnostic Pathology | Full Text

  https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-020-01017-8

  The virus enters the cell by attaching its spike-like surface projections to the angiotensin-converting enzyme-2 (ACE-2) expressed in various tissues. […] A few pathology studies have also reported intravascular microthrombi and pulmonary thrombembolism. […] Envelope-based spike protein (S protein) is the principal determinant of virulence. […] The S protein is cleaved at the S2 site, present just adjacent to fusion peptide by host protease TMPRSS2. […] For SARS-CoV and SARS-CoV-2, the receptor is ACE-2. […] SARS-CoV-2 has a higher affinity for the receptor (10 to 20 times greater than SARS-CoV), favoring rapid spread among the human population. […] Importantly, there is evidence from SARS-CoV that blood group antigen A may directly interact with the viral S protein, thus facilitating virus entry via ACE-2.

• #10 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  The primary target cells of SARS-CoV infection are respiratory epithelial cells. […] The SARS-CoV target cell specificity is determined by the spike protein affinity to cellular receptors. […] After binding to the receptor, the next molecular step of potential use for the development of anti-SARS drugs is the virus entry into the cells. […] After the binding to a host cell receptor and entry into the cells, the molecular steps of transcription, translation and protein processing display further potential targets for new therapeutic strategies. […] The structural proteins of the new SARS-CoV are potential targets for new treatment options.

• #11 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  The primary target cells of SARS-CoV infection are respiratory epithelial cells. […] The SARS-CoV target cell specificity is determined by the spike protein affinity to cellular receptors. […] After binding to the receptor, the next molecular step of potential use for the development of anti-SARS drugs is the virus entry into the cells. […] After the binding to a host cell receptor and entry into the cells, the molecular steps of transcription, translation and protein processing display further potential targets for new therapeutic strategies. […] The structural proteins of the new SARS-CoV are potential targets for new treatment options.

• #12 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  The first cells targeted by SARS-CoV-2 during natural infection in humans are likely to be multiciliated cells in the nasopharynx or trachea, or sustentacular cells in the nasal olfactory mucosa. […] After entry, the positive-sense SARS-CoV-2 genome directly initiates the production of viral proteins, including the replicase proteins that form replication factories from endoplasmic reticulum membranes. […] The main cytoplasmic PRR capable of detecting SARS-CoV-2 is thought to be MDA5, which recognizes long dsRNAs and initiates a signalling cascade to promote the transcription of type I and type III interferons. […] If the virus is not cleared by innate or adaptive responses, it can spread to the lower respiratory tract by inhalation of virus particles from the upper respiratory tract or by gradual dissemination along the tracheobronchial tree.

• #13 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.

• #14 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.

• #15

  https://link.springer.com/article/10.1007/s13337-021-00687-2

  The entry of enveloped viruses readily occurs at the cell surface by receptor binding or endocytosis mediated internalization. The CoV spike proteins (S) are class I fusion proteins that facilitate viral attachment and fusion of host and viral membranes. […] The binding of CoVs is followed by the release of the viral genome into the host cell. […] The replication of the CoV genome begins with the translation of replicase gene that codes for two open reading frames (ORFs) ORF1a and ORF1b and the translation product of ORF 1a includes Nsps from Nsp1- Nsp11 and for ORF 1b from Nsp12- Nsp16 along with Nsp1-11 altogether forming the RTC. […] The presence of replication organelles is a characteristic feature of CoV replication. […] The CoV interferes with the host cell secretory pathway to transport and deliver the cargo virus protein at the final packaging site and budding after forming a complete virus particle.

• #16

  https://link.springer.com/article/10.1007/s13337-021-00687-2

  The entry of enveloped viruses readily occurs at the cell surface by receptor binding or endocytosis mediated internalization. The CoV spike proteins (S) are class I fusion proteins that facilitate viral attachment and fusion of host and viral membranes. […] The binding of CoVs is followed by the release of the viral genome into the host cell. […] The replication of the CoV genome begins with the translation of replicase gene that codes for two open reading frames (ORFs) ORF1a and ORF1b and the translation product of ORF 1a includes Nsps from Nsp1- Nsp11 and for ORF 1b from Nsp12- Nsp16 along with Nsp1-11 altogether forming the RTC. […] The presence of replication organelles is a characteristic feature of CoV replication. […] The CoV interferes with the host cell secretory pathway to transport and deliver the cargo virus protein at the final packaging site and budding after forming a complete virus particle.

• #17

  https://link.springer.com/article/10.1007/s13337-021-00687-2

  The entry of enveloped viruses readily occurs at the cell surface by receptor binding or endocytosis mediated internalization. The CoV spike proteins (S) are class I fusion proteins that facilitate viral attachment and fusion of host and viral membranes. […] The binding of CoVs is followed by the release of the viral genome into the host cell. […] The replication of the CoV genome begins with the translation of replicase gene that codes for two open reading frames (ORFs) ORF1a and ORF1b and the translation product of ORF 1a includes Nsps from Nsp1- Nsp11 and for ORF 1b from Nsp12- Nsp16 along with Nsp1-11 altogether forming the RTC. […] The presence of replication organelles is a characteristic feature of CoV replication. […] The CoV interferes with the host cell secretory pathway to transport and deliver the cargo virus protein at the final packaging site and budding after forming a complete virus particle.

• #18 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  In the alveoli, SARS-CoV-2 has been shown to primarily infect alveolar type 2 (AT2) cells both in vivo and in vitro. […] The clinical syndrome ARDS can be caused by a wide range of predisposing factors, including viral infection. […] Histological examination of lung tissues of deceased individuals with COVID-19 on autopsy show that DAD is the predominant pattern of lung injury. […] Alveolar cell death or damage leads to a disruption of the alveolar epithelium, which sets off another key feature of the exudative phase of DAD seen in COVID-19: an imbalance between the activation of coagulation and the inhibition of fibrinolysis. […] The prothrombotic state seen in patients with COVID-19 is reminiscent of a process known as immunothrombosis, in which the immune and coagulation systems cooperate to block pathogens and limit their spread.

• #19 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  In the alveoli, SARS-CoV-2 has been shown to primarily infect alveolar type 2 (AT2) cells both in vivo and in vitro. […] The clinical syndrome ARDS can be caused by a wide range of predisposing factors, including viral infection. […] Histological examination of lung tissues of deceased individuals with COVID-19 on autopsy show that DAD is the predominant pattern of lung injury. […] Alveolar cell death or damage leads to a disruption of the alveolar epithelium, which sets off another key feature of the exudative phase of DAD seen in COVID-19: an imbalance between the activation of coagulation and the inhibition of fibrinolysis. […] The prothrombotic state seen in patients with COVID-19 is reminiscent of a process known as immunothrombosis, in which the immune and coagulation systems cooperate to block pathogens and limit their spread.

• #20 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  In the alveoli, SARS-CoV-2 has been shown to primarily infect alveolar type 2 (AT2) cells both in vivo and in vitro. […] The clinical syndrome ARDS can be caused by a wide range of predisposing factors, including viral infection. […] Histological examination of lung tissues of deceased individuals with COVID-19 on autopsy show that DAD is the predominant pattern of lung injury. […] Alveolar cell death or damage leads to a disruption of the alveolar epithelium, which sets off another key feature of the exudative phase of DAD seen in COVID-19: an imbalance between the activation of coagulation and the inhibition of fibrinolysis. […] The prothrombotic state seen in patients with COVID-19 is reminiscent of a process known as immunothrombosis, in which the immune and coagulation systems cooperate to block pathogens and limit their spread.

• #21 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  In the alveoli, SARS-CoV-2 has been shown to primarily infect alveolar type 2 (AT2) cells both in vivo and in vitro. […] The clinical syndrome ARDS can be caused by a wide range of predisposing factors, including viral infection. […] Histological examination of lung tissues of deceased individuals with COVID-19 on autopsy show that DAD is the predominant pattern of lung injury. […] Alveolar cell death or damage leads to a disruption of the alveolar epithelium, which sets off another key feature of the exudative phase of DAD seen in COVID-19: an imbalance between the activation of coagulation and the inhibition of fibrinolysis. […] The prothrombotic state seen in patients with COVID-19 is reminiscent of a process known as immunothrombosis, in which the immune and coagulation systems cooperate to block pathogens and limit their spread.

• #22 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  What triggers the imbalance in the coagulation system in COVID-19 is currently poorly understood, but it may start with the disruption of the alveolar epithelium. […] These stimuli trigger endothelial activation and may lead to endothelial cell death, which has been observed in COVID-19 cases. […] The disrupted epithelium and endothelium allow fluid to leak into the alveoli. […] The exposed subendothelial extracellular matrix attracts and activates platelets and initiates the coagulation cascade, leading to fibrin deposition. […] Overall, it seems that type I and type III interferons protect against severe coronavirus-induced pneumonia when their expression or administration is timed correctly.

• #23 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  What triggers the imbalance in the coagulation system in COVID-19 is currently poorly understood, but it may start with the disruption of the alveolar epithelium. […] These stimuli trigger endothelial activation and may lead to endothelial cell death, which has been observed in COVID-19 cases. […] The disrupted epithelium and endothelium allow fluid to leak into the alveoli. […] The exposed subendothelial extracellular matrix attracts and activates platelets and initiates the coagulation cascade, leading to fibrin deposition. […] Overall, it seems that type I and type III interferons protect against severe coronavirus-induced pneumonia when their expression or administration is timed correctly.

• #24 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] Coronaviruses are known to exert their effects by cytocidal and immune-mediated mechanisms. In vitro studies using cell culture assays have shown that coronavirus infection commonly results in cytopathic effects such as cellular lysis or apoptosis. […] Also, immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] The most obvious gene which is likely to be a key modifier of SARS pathomechanisms is the spike (S) protein gene.

• #25 SARS – Wikipedia

  https://en.wikipedia.org/wiki/SARS

  Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the virus SARS-CoV-1, the first identified strain of the SARS-related coronavirus. […] SARS-CoV may be suspected in a patient who has any of the symptoms, including a fever of 38 C (100 F) or higher. […] The appearance of SARS-CoV in chest X-rays is not always uniform but generally appears as an abnormality with patchy infiltrates. […] Some of the more serious damage caused by SARS may be due to the body’s own immune system reacting in what is known as cytokine storm. […] In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats. […] Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets.

• #26 SARS-CoV-2 pathogenesis | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-022-00713-0

  The first cells targeted by SARS-CoV-2 during natural infection in humans are likely to be multiciliated cells in the nasopharynx or trachea, or sustentacular cells in the nasal olfactory mucosa. […] After entry, the positive-sense SARS-CoV-2 genome directly initiates the production of viral proteins, including the replicase proteins that form replication factories from endoplasmic reticulum membranes. […] The main cytoplasmic PRR capable of detecting SARS-CoV-2 is thought to be MDA5, which recognizes long dsRNAs and initiates a signalling cascade to promote the transcription of type I and type III interferons. […] If the virus is not cleared by innate or adaptive responses, it can spread to the lower respiratory tract by inhalation of virus particles from the upper respiratory tract or by gradual dissemination along the tracheobronchial tree.

• #27 SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000849

  Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. […] This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. […] These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. […] Our data reveals a new mechanistic pathway by which STAT1 regulates the severity of viral pathogenesis in the lung. […] We show that SARS-CoV pathogenesis is STAT1 dependent but independent of type I, II and III IFN signaling, and we provide evidence consistent with an essential role for STAT1 in the control of SARS-CoV replication, cell proliferation, wound repair and progression to severe organizing phase DAD and lethal disease. […] We propose a new potential pathway by which STAT1 regulates end stage lung disease following viral infection. […] Our findings also point to an increasing role of the cell damage response to viral infection that can be potential targets for therapy in highly pathogenic respiratory infections.

• #28 SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000849

  Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. […] This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. […] These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. […] Our data reveals a new mechanistic pathway by which STAT1 regulates the severity of viral pathogenesis in the lung. […] We show that SARS-CoV pathogenesis is STAT1 dependent but independent of type I, II and III IFN signaling, and we provide evidence consistent with an essential role for STAT1 in the control of SARS-CoV replication, cell proliferation, wound repair and progression to severe organizing phase DAD and lethal disease. […] We propose a new potential pathway by which STAT1 regulates end stage lung disease following viral infection. […] Our findings also point to an increasing role of the cell damage response to viral infection that can be potential targets for therapy in highly pathogenic respiratory infections.

• #29 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.

• #30 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  Although recent evidence shows that the SARS-CoV accessory genes are expressed in the host during infection, their functions remain somewhat obscure. Currently, there are a range of proposed functions for these accessory proteins, including modulation of viral pathogenicity and replication, as well as acting as cell death inducers and interferon (IFN) antagonists, to name a few. […] The occurrence of both apoptosis and necrosis in host cells during SARS-CoV infection suggests that the regulation of cell death is important for viral replication and/or pathogenesis. The pro-apoptotic function of ORF3a is reliant on its ion channel activity and is induced via caspase-8 and -9 dependent pathways. […] Even though the natural animal reservoir for SARS-CoV has not been identified, the threat of another SARS outbreak is still a disturbing possibility as bats have been shown to be natural reservoirs for different SARS-like coronaviruses (SL-CoV).

• #31 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  Although recent evidence shows that the SARS-CoV accessory genes are expressed in the host during infection, their functions remain somewhat obscure. Currently, there are a range of proposed functions for these accessory proteins, including modulation of viral pathogenicity and replication, as well as acting as cell death inducers and interferon (IFN) antagonists, to name a few. […] The occurrence of both apoptosis and necrosis in host cells during SARS-CoV infection suggests that the regulation of cell death is important for viral replication and/or pathogenesis. The pro-apoptotic function of ORF3a is reliant on its ion channel activity and is induced via caspase-8 and -9 dependent pathways. […] Even though the natural animal reservoir for SARS-CoV has not been identified, the threat of another SARS outbreak is still a disturbing possibility as bats have been shown to be natural reservoirs for different SARS-like coronaviruses (SL-CoV).

• #32 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  SARS-CoV is the prototype human CoV and has been studied extensively. In addition, SARS-CoV contains eight encoded accessory genes interspersed amongst the viral structural genes, the most of the known CoVs. Interestingly, these accessory genes are present in SARS-CoVs isolated from bats, civet cats, raccoon dogs, and humans, suggesting important accessory functions in a variety of hosts. Evidence confirms that these accessory proteins are indeed expressed during SARS-CoV infection, but for many, their functions are yet to be determined. Five of the SARS-CoV accessory proteins (ORF3a, -6, -7a, -7b and -9b) have been identified as minor viral structural components, and others induce ion channels, act as cell death inducers and IFN antagonists. It would be interesting to determine whether the high SARS-CoV accessory gene number correlate with the increased virulence of SARS-CoV when compared to the other known human CoVs. For this reason, the role of the accessory proteins in pathogenesis must be elucidated.

• #33 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] Coronaviruses are known to exert their effects by cytocidal and immune-mediated mechanisms. In vitro studies using cell culture assays have shown that coronavirus infection commonly results in cytopathic effects such as cellular lysis or apoptosis. […] Also, immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] The most obvious gene which is likely to be a key modifier of SARS pathomechanisms is the spike (S) protein gene.

• #34 Molecular mechanisms of severe acute respiratory syndrome (SARS) | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] Coronaviruses are known to exert their effects by cytocidal and immune-mediated mechanisms. In vitro studies using cell culture assays have shown that coronavirus infection commonly results in cytopathic effects such as cellular lysis or apoptosis. […] Also, immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] The most obvious gene which is likely to be a key modifier of SARS pathomechanisms is the spike (S) protein gene.

• #35

  https://link.springer.com/article/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] SARS-CoV has been shown to cause cytopathic effects in Vero cells and the formation of syncytia in lung tissues. A further similarity with other coronaviruses seems to be the potential of the SARS-CoV to cause tissue fibrosis. […] Next to cytocidal effects, also immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] It is therefore crucial that these immune mechanisms are further analysed on the molecular level as it seems appropriate that not only antiviral but also anti-inflammatory strategies are evaluated for a use in the clinical management of future SARS cases.

• #36

  https://link.springer.com/article/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] SARS-CoV has been shown to cause cytopathic effects in Vero cells and the formation of syncytia in lung tissues. A further similarity with other coronaviruses seems to be the potential of the SARS-CoV to cause tissue fibrosis. […] Next to cytocidal effects, also immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] It is therefore crucial that these immune mechanisms are further analysed on the molecular level as it seems appropriate that not only antiviral but also anti-inflammatory strategies are evaluated for a use in the clinical management of future SARS cases.

• #37 The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

  https://www.mdpi.com/1999-4915/4/11/2902

  Although recent evidence shows that the SARS-CoV accessory genes are expressed in the host during infection, their functions remain somewhat obscure. Currently, there are a range of proposed functions for these accessory proteins, including modulation of viral pathogenicity and replication, as well as acting as cell death inducers and interferon (IFN) antagonists, to name a few. […] The occurrence of both apoptosis and necrosis in host cells during SARS-CoV infection suggests that the regulation of cell death is important for viral replication and/or pathogenesis. The pro-apoptotic function of ORF3a is reliant on its ion channel activity and is induced via caspase-8 and -9 dependent pathways. […] Even though the natural animal reservoir for SARS-CoV has not been identified, the threat of another SARS outbreak is still a disturbing possibility as bats have been shown to be natural reservoirs for different SARS-like coronaviruses (SL-CoV).

• #38 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #39 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #40 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #41 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #42 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #43 Coronaviruses and Acute Respiratory Syndromes (MERS and SARS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/respiratory-viruses/coronaviruses-and-acute-respiratory-syndromes-mers-and-sars

  Severe acute respiratory syndrome (SARS) is a severe, acute respiratory illness caused by the SARS coronavirus (SARS-CoV-1). […] SARS is a severe coronavirus infection with a case fatality rate of approximately 15%, but the fatality rate much higher in older adults. […] SARS-CoV-1 was first detected in the Guangdong province of China in November 2002 and subsequently spread to 28 additional countries. […] The immediate source was presumed to be civet cats, that were being sold for food in a live-animal market and had likely been infected through contact with a bat before they were captured for sale. […] SARS-CoV-1 is transmitted from person to person by close personal contact. […] It is thought to be transmitted most readily by respiratory droplets produced when an infected person coughs or sneezes. […] Diagnosis of SARS is made clinically, and treatment is supportive. […] Although no new cases have been reported since 2004, SARS should not be considered eliminated because the causative virus has an animal reservoir from which it conceivably could reemerge.

• #44

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-coronavirus. […] The pathogen causing the disease was identified as a coronavirus at the end of February 2003. […] SARS-CoV-1 (the number 1 was added later to distinguish it from the recently emerged SARS-CoV-2) is a respiratory virus which can spread through the air through small infectious respiratory particles. […] SARS can also be transmitted indirectly through deposition of the virus onto surfaces via contaminated surfaces that have been touched by someone who is infected with the virus. […] The case fatality among persons with illness meeting the current WHO case definition for confirmed cases of SARS is around 9.6%. […] After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnoea (shortness of breath) that may be accompanied by, or progress to, hypoxemia (low blood oxygen levels).

• #45 Coronaviruses and Acute Respiratory Syndromes (MERS and SARS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/respiratory-viruses/coronaviruses-and-acute-respiratory-syndromes-mers-and-sars

  Severe acute respiratory syndrome (SARS) is a severe, acute respiratory illness caused by the SARS coronavirus (SARS-CoV-1). […] SARS is a severe coronavirus infection with a case fatality rate of approximately 15%, but the fatality rate much higher in older adults. […] SARS-CoV-1 was first detected in the Guangdong province of China in November 2002 and subsequently spread to 28 additional countries. […] The immediate source was presumed to be civet cats, that were being sold for food in a live-animal market and had likely been infected through contact with a bat before they were captured for sale. […] SARS-CoV-1 is transmitted from person to person by close personal contact. […] It is thought to be transmitted most readily by respiratory droplets produced when an infected person coughs or sneezes. […] Diagnosis of SARS is made clinically, and treatment is supportive. […] Although no new cases have been reported since 2004, SARS should not be considered eliminated because the causative virus has an animal reservoir from which it conceivably could reemerge.

• #46 Severe acute respiratory syndrome (SARS) – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/sars/symptoms-causes/syc-20351765

  Severe acute respiratory syndrome (SARS) is a contagious illness caused by a coronavirus. Its a disease that affects the lungs and airways, also called a respiratory illness. The coronavirus that causes SARS is called SARS-CoV-1. It first appeared in November 2002. Within a few months, the SARS-CoV-1 virus spread worldwide. It mainly passed from person to person. […] SARS is caused by SARS-CoV-1, a strain of coronavirus. Coronaviruses are the family of viruses that also cause the common cold. A different strain of coronavirus, called SARS-CoV-2, causes COVID-19. […] Most viruses that cause respiratory illnesses, including SARS, spread when infected people cough, sneeze or talk. Tiny liquid particles from the nose or mouth enter the air. Healthy people nearby breathe in those particles. Most experts think the virus that causes SARS spreads mainly through close personal contact. For instance, a healthy person could get infected while taking care of someone who has SARS.

• #47 Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States – Volume 26, Number 9—September 2020 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/26/9/20-2095_article

  These findings corroborate reports of high viral loads in the upper respiratory tract and support the potential for persons infected with SARS-CoV-2 to readily transmit the virus, with prolonged and continued viral shedding in severe cases. […] Overall pathologic features in these 8 COVID-19 deaths were similar to those seen in SARS-CoV and MERS-CoV infections, and in available COVID-19 reports. […] However, the amount of viral antigen detected by IHC in lung tissue from these cases is more than what we have seen in SARS and MERS cases submitted to our laboratory, and its extensive detection in epithelial cells of the upper respiratory tract is unique among these highly pathogenic coronaviruses. […] In addition to direct viral effects on tissues, the immune response to viral infection likely plays a major role in determining clinical outcome, and acute decline in COVID-19 patients has been linked to an immune-mediated cytokine storm.

• #48 SARS and MERS | BCM

  https://www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-infections-and-biodefense/specific-agents/sars-mers

  SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) are serious infectious respiratory diseases that are caused by members of a class of viruses known as coronaviruses. […] SARS is characterized by severe, pneumonia-like symptoms which can be fatal. […] SARS-CoV was transmitted from person to person mainly through respiratory droplets produced when a person sneezes or coughs and through direct contact with a surface contaminated with infected respiratory droplets. […] One reason that SARS-CoV might have been more lethal than other coronaviruses is that it appears to interfere with an enzyme system in humans that is critical for regulating body fluid balance. Therefore, the virus could disrupt normal functioning of the lungs by blocking this enzyme system and allowing fluid to leak into the air sacs of the lungs, resulting in severe respiratory illness.

• #49

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-coronavirus. […] The pathogen causing the disease was identified as a coronavirus at the end of February 2003. […] SARS-CoV-1 (the number 1 was added later to distinguish it from the recently emerged SARS-CoV-2) is a respiratory virus which can spread through the air through small infectious respiratory particles. […] SARS can also be transmitted indirectly through deposition of the virus onto surfaces via contaminated surfaces that have been touched by someone who is infected with the virus. […] The case fatality among persons with illness meeting the current WHO case definition for confirmed cases of SARS is around 9.6%. […] After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnoea (shortness of breath) that may be accompanied by, or progress to, hypoxemia (low blood oxygen levels).

• #50

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-coronavirus. […] The pathogen causing the disease was identified as a coronavirus at the end of February 2003. […] SARS-CoV-1 (the number 1 was added later to distinguish it from the recently emerged SARS-CoV-2) is a respiratory virus which can spread through the air through small infectious respiratory particles. […] SARS can also be transmitted indirectly through deposition of the virus onto surfaces via contaminated surfaces that have been touched by someone who is infected with the virus. […] The case fatality among persons with illness meeting the current WHO case definition for confirmed cases of SARS is around 9.6%. […] After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnoea (shortness of breath) that may be accompanied by, or progress to, hypoxemia (low blood oxygen levels).

• #51

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  In 10-20% of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation. […] Antivirals such as polymerase and protease inhibitors against SARS-CoV-2 are likely to be effective against SARS-CoV-1. […] COVID-19 vaccines may provide some level of cross-protection against SARS; however, the extent of such cross-protection remains to be studied.

• #52 Severe acute respiratory syndrome (SARS): MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/007192.htm

  Symptoms usually occur 2 to 10 days after coming in contact with the virus. People with active symptoms of illness are contagious. But it is not known for how long a person may be contagious after symptoms appear. […] In most people with SARS, a chest x-ray or chest CT scan show pneumonia, which is typical with SARS. […] In some serious cases, the liquid part of blood from people who have already recovered from SARS has been given as a treatment. […] There is no strong evidence that these treatments work well. There is evidence that the antiviral medicine, ribavirin, does not work. Newer antivirals have not been tried as the disease has not occurred recently. […] In the 2003 outbreak, the death rate from SARS was 9% to 12% of those diagnosed. In people over age 65, the death rate was higher than 50%. The illness was milder in younger people. […] Public health policies were effective at controlling outbreaks of SARS. Since 2004, there have been no cases of SARS reported anywhere in the world. […] Complications may include: Respiratory failure, Liver failure, Heart failure, Kidney problems.

• #53 Severe acute respiratory syndrome (SARS): MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/007192.htm

  Symptoms usually occur 2 to 10 days after coming in contact with the virus. People with active symptoms of illness are contagious. But it is not known for how long a person may be contagious after symptoms appear. […] In most people with SARS, a chest x-ray or chest CT scan show pneumonia, which is typical with SARS. […] In some serious cases, the liquid part of blood from people who have already recovered from SARS has been given as a treatment. […] There is no strong evidence that these treatments work well. There is evidence that the antiviral medicine, ribavirin, does not work. Newer antivirals have not been tried as the disease has not occurred recently. […] In the 2003 outbreak, the death rate from SARS was 9% to 12% of those diagnosed. In people over age 65, the death rate was higher than 50%. The illness was milder in younger people. […] Public health policies were effective at controlling outbreaks of SARS. Since 2004, there have been no cases of SARS reported anywhere in the world. […] Complications may include: Respiratory failure, Liver failure, Heart failure, Kidney problems.

• #54 Severe acute respiratory syndrome (SARS): MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/007192.htm

  Symptoms usually occur 2 to 10 days after coming in contact with the virus. People with active symptoms of illness are contagious. But it is not known for how long a person may be contagious after symptoms appear. […] In most people with SARS, a chest x-ray or chest CT scan show pneumonia, which is typical with SARS. […] In some serious cases, the liquid part of blood from people who have already recovered from SARS has been given as a treatment. […] There is no strong evidence that these treatments work well. There is evidence that the antiviral medicine, ribavirin, does not work. Newer antivirals have not been tried as the disease has not occurred recently. […] In the 2003 outbreak, the death rate from SARS was 9% to 12% of those diagnosed. In people over age 65, the death rate was higher than 50%. The illness was milder in younger people. […] Public health policies were effective at controlling outbreaks of SARS. Since 2004, there have been no cases of SARS reported anywhere in the world. […] Complications may include: Respiratory failure, Liver failure, Heart failure, Kidney problems.

• #55 Severe acute respiratory syndrome (SARS) – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/sars/symptoms-causes/syc-20351765

  Many people with SARS get pneumonia. And sometimes, a machine called a ventilator is needed to help with breathing. SARS is fatal in some cases, often because the body cant get enough oxygen or cant remove enough carbon dioxide. This condition is called respiratory failure. SARS also can lead to heart and liver failure.

• #56 Severe acute respiratory syndrome (SARS) – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/sars/symptoms-causes/syc-20351765

  Many people with SARS get pneumonia. And sometimes, a machine called a ventilator is needed to help with breathing. SARS is fatal in some cases, often because the body cant get enough oxygen or cant remove enough carbon dioxide. This condition is called respiratory failure. SARS also can lead to heart and liver failure.

• #57 Severe acute respiratory syndrome (SARS) – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/sars/symptoms-causes/syc-20351765

  Many people with SARS get pneumonia. And sometimes, a machine called a ventilator is needed to help with breathing. SARS is fatal in some cases, often because the body cant get enough oxygen or cant remove enough carbon dioxide. This condition is called respiratory failure. SARS also can lead to heart and liver failure.

• #58 Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008949

  The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 57 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. […] Understanding the viral infection process is the first step of all effective means to control the disease and develop vaccines. In this case, establishing an effective animal model of SARS-CoV-2 infection can not only help us understand the pathological characteristics of COVID-19, but also help to clarify the viral systematic pathologic process induced by infection.

• #59 Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008949

  The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 57 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. […] Understanding the viral infection process is the first step of all effective means to control the disease and develop vaccines. In this case, establishing an effective animal model of SARS-CoV-2 infection can not only help us understand the pathological characteristics of COVID-19, but also help to clarify the viral systematic pathologic process induced by infection.

• #60 Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008949

  In our study, the nasally-infected rhesus macaques displayed similar clinical and pathological manifestation of COVID-19, especially lower respiratory tract disease proceeding from mild to marked pneumonia. […] In this rhesus macaque model, the progression of pneumonia was recapitulated and displayed typical pathology of interstitial infiltration with diffused alveolar damage in the lung. […] In our rhesus macaque model, we found that a proportion of T cells, including Th1/Th2/Th17 cells, displayed a reduction during the middle and late stages of infection, while the CD4+FOXP3+T cell response was activated during this period. […] In this study, local cytokines/chemokines in lung, such as IFN-, IL-4, IL-6, IL-1, MCP-1, and IL-8, MIP-1a, were increased by more than 2-fold within 3 days post SARS-CoV-2 infection. […] Collectively, our data show that some proinflammatory cytokines and Th1 and Th2 cytokines might play a certain role in SARS-COV-2 infection.

• #61 Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008949

  In our study, the nasally-infected rhesus macaques displayed similar clinical and pathological manifestation of COVID-19, especially lower respiratory tract disease proceeding from mild to marked pneumonia. […] In this rhesus macaque model, the progression of pneumonia was recapitulated and displayed typical pathology of interstitial infiltration with diffused alveolar damage in the lung. […] In our rhesus macaque model, we found that a proportion of T cells, including Th1/Th2/Th17 cells, displayed a reduction during the middle and late stages of infection, while the CD4+FOXP3+T cell response was activated during this period. […] In this study, local cytokines/chemokines in lung, such as IFN-, IL-4, IL-6, IL-1, MCP-1, and IL-8, MIP-1a, were increased by more than 2-fold within 3 days post SARS-CoV-2 infection. […] Collectively, our data show that some proinflammatory cytokines and Th1 and Th2 cytokines might play a certain role in SARS-COV-2 infection.

• #62 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Despite their contributions to our understanding of viral pathogenesis, the development of vaccines, and antiviral therapies, animal models demonstrated significant translational gaps when predicting human responses. […] Given the logistical, scientific, ethical, and safety concerns surrounding traditional animal models, particularly during a global health crisis, there is an increasing impetus to explore alternative approaches that provide faster, more reliable insights into human physiology and disease mechanisms while ensuring enhanced biosafety. […] Brain organoid-based studies have provided crucial insights into the neurotropism, replication dynamics, and pathogenic effects of SARS-CoV-2, highlighting its potential impact on the central nervous system (CNS). […] These findings suggest that the choroid plexus may act as a critical entry point for SARS-CoV-2 into the CNS, potentially contributing to the neurological complications observed in COVID-19 patients.

• #63 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Despite their contributions to our understanding of viral pathogenesis, the development of vaccines, and antiviral therapies, animal models demonstrated significant translational gaps when predicting human responses. […] Given the logistical, scientific, ethical, and safety concerns surrounding traditional animal models, particularly during a global health crisis, there is an increasing impetus to explore alternative approaches that provide faster, more reliable insights into human physiology and disease mechanisms while ensuring enhanced biosafety. […] Brain organoid-based studies have provided crucial insights into the neurotropism, replication dynamics, and pathogenic effects of SARS-CoV-2, highlighting its potential impact on the central nervous system (CNS). […] These findings suggest that the choroid plexus may act as a critical entry point for SARS-CoV-2 into the CNS, potentially contributing to the neurological complications observed in COVID-19 patients.

• #64 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Despite their contributions to our understanding of viral pathogenesis, the development of vaccines, and antiviral therapies, animal models demonstrated significant translational gaps when predicting human responses. […] Given the logistical, scientific, ethical, and safety concerns surrounding traditional animal models, particularly during a global health crisis, there is an increasing impetus to explore alternative approaches that provide faster, more reliable insights into human physiology and disease mechanisms while ensuring enhanced biosafety. […] Brain organoid-based studies have provided crucial insights into the neurotropism, replication dynamics, and pathogenic effects of SARS-CoV-2, highlighting its potential impact on the central nervous system (CNS). […] These findings suggest that the choroid plexus may act as a critical entry point for SARS-CoV-2 into the CNS, potentially contributing to the neurological complications observed in COVID-19 patients.

• #65 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Despite their contributions to our understanding of viral pathogenesis, the development of vaccines, and antiviral therapies, animal models demonstrated significant translational gaps when predicting human responses. […] Given the logistical, scientific, ethical, and safety concerns surrounding traditional animal models, particularly during a global health crisis, there is an increasing impetus to explore alternative approaches that provide faster, more reliable insights into human physiology and disease mechanisms while ensuring enhanced biosafety. […] Brain organoid-based studies have provided crucial insights into the neurotropism, replication dynamics, and pathogenic effects of SARS-CoV-2, highlighting its potential impact on the central nervous system (CNS). […] These findings suggest that the choroid plexus may act as a critical entry point for SARS-CoV-2 into the CNS, potentially contributing to the neurological complications observed in COVID-19 patients.

• #66 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Infected brain organoids demonstrated upregulated inflammatory gene expression, structural disorganization, and disrupted neural differentiation, indicating potential neurodevelopmental and neurodegenerative consequences of viral infection. […] SARS-CoV-2 has been shown to efficiently infect and replicate within these organoids, leading to epithelial damage, ciliary dysfunction, and dysregulated inflammatory responses, closely resembling in vivo lung pathology. […] These findings emphasize the critical role of gastrointestinal and renal organoids in studying COVID-19 complications, identifying patient-specific vulnerabilities, and evaluating potential therapeutic strategies for high-risk populations. […] The ability of these models to recapitulate disease pathology, assess metabolic influences on viral infection, and serve as platforms for targeted drug discovery highlights their importance in advancing our understanding of SARS-CoV-2 pathogenesis and treatment strategies.

• #67 Perspective Chapter: A New Era in Viral Research during the Pandemic – Can Organoids Serve as an Alternative to Animal Models? | IntechOpen

  https://www.intechopen.com/online-first/1211513

  Infected brain organoids demonstrated upregulated inflammatory gene expression, structural disorganization, and disrupted neural differentiation, indicating potential neurodevelopmental and neurodegenerative consequences of viral infection. […] SARS-CoV-2 has been shown to efficiently infect and replicate within these organoids, leading to epithelial damage, ciliary dysfunction, and dysregulated inflammatory responses, closely resembling in vivo lung pathology. […] These findings emphasize the critical role of gastrointestinal and renal organoids in studying COVID-19 complications, identifying patient-specific vulnerabilities, and evaluating potential therapeutic strategies for high-risk populations. […] The ability of these models to recapitulate disease pathology, assess metabolic influences on viral infection, and serve as platforms for targeted drug discovery highlights their importance in advancing our understanding of SARS-CoV-2 pathogenesis and treatment strategies.

• #68 Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7167902/

  There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. […] Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. […] Therefore, other virus receptors or coreceptors may be required in different tissues. […] It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. […] The discovery and characterization of cellular receptor of SARSCoV might provide important clues to the pathogenesis of this novel virus. […] The general pattern of ACE2 expression correlates roughly with the tropism of SARSCoV in fatal cases. […] It is apparent that the effect of SARSCoV infection is different in different cell types and it is possible that the virus may utilize different receptors, or involve various coreceptors, in these different cells. […] The interaction between SARSCoV and the immunological or lymphoid system needs to be defined. […] Further insights into the pathogenesis of SARSCoV may be gained from emerging new human cell culture models.

• #69

  https://link.springer.com/article/10.1186/1465-9921-6-8

  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. […] With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. […] SARS-CoV has been shown to cause cytopathic effects in Vero cells and the formation of syncytia in lung tissues. A further similarity with other coronaviruses seems to be the potential of the SARS-CoV to cause tissue fibrosis. […] Next to cytocidal effects, also immune-mediated mechanisms of both the innate and adaptive immune system seem to contribute to the pathogenesis of SARS-CoV infections. […] It is therefore crucial that these immune mechanisms are further analysed on the molecular level as it seems appropriate that not only antiviral but also anti-inflammatory strategies are evaluated for a use in the clinical management of future SARS cases.

• #70 Severe Acute Respiratory Syndrome (SARS)

  https://my.clevelandclinic.org/health/diseases/10856-severe-acute-respiratory-syndrome-sars

  No, there isnt a cure for SARS. And like many viruses, there arent any specific antiviral medications that treat it. […] Public health measures helped contain SARS. Scientists collaborated to quickly identify and find ways to test for the virus. SARS is most contagious after symptoms start, so screening people with symptoms and isolating them at home was effective at containing the spread.

• #71 Severe Acute Respiratory Syndrome (SARS)

  https://my.clevelandclinic.org/health/diseases/10856-severe-acute-respiratory-syndrome-sars

  No, there isnt a cure for SARS. And like many viruses, there arent any specific antiviral medications that treat it. […] Public health measures helped contain SARS. Scientists collaborated to quickly identify and find ways to test for the virus. SARS is most contagious after symptoms start, so screening people with symptoms and isolating them at home was effective at containing the spread.

• #72

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  In 10-20% of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation. […] Antivirals such as polymerase and protease inhibitors against SARS-CoV-2 are likely to be effective against SARS-CoV-1. […] COVID-19 vaccines may provide some level of cross-protection against SARS; however, the extent of such cross-protection remains to be studied.

• #73

  https://www.who.int/health-topics/severe-acute-respiratory-syndrome

  In 10-20% of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation. […] Antivirals such as polymerase and protease inhibitors against SARS-CoV-2 are likely to be effective against SARS-CoV-1. […] COVID-19 vaccines may provide some level of cross-protection against SARS; however, the extent of such cross-protection remains to be studied.

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