LitCovid-sentences  

PMC:7736111 / 37852-43398 JSONTXT 3 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T217 0-28 Sentence denotes Impaired Interferon Response
T218 29-713 Sentence denotes Based on previous molecular and clinical studies on SARS-CoV and the recent data on SARS-CoV-2, it is becoming evident that the delay in primary IFN response may be due to multiple factors such as (1) poor overall immune function of a patient with a compromised adaptive response as in older people, (2) patients with comorbidity, (3) genetic factors or epigenetic changes associated with crucial genes and transcriptional factors involved in IFN signaling, and (4) age and sex of the patient, probably making the older individuals and males more susceptible to COVID-19 (Bastard et al., 2020; Li M.Y. et al., 2020; Nguyen et al., 2020; Verdecchia et al., 2020; Zhou F. et al., 2020).
T219 714-824 Sentence denotes Thus, overall these factors may compromise the host cell immune system and delay the early antiviral response.
T220 825-979 Sentence denotes Especially in the case of RNA viruses, evasion of host immune response is managed by interfering with PRRs, PLRs, TLRs, and IFN signaling (Kikkert, 2020).
T221 980-1132 Sentence denotes Additionally, inhibition is also conferred by hijacking host cell biosynthetic machinery and eventually inducing host cell apoptosis as discussed above.
T222 1133-1333 Sentence denotes Previous studies have unequivocally demonstrated poor IFN response to SARS-CoV during severe infection, which is also apparently the case with SARS-CoV-2, reviewed recently by Park and Iwasaki (2020).
T223 1334-1479 Sentence denotes In vitro culture of the primary lung, epithelial cells infected with the SARS-CoV-2 generated inadequate IFN response (Blanco-Melo et al., 2020).
T224 1480-1616 Sentence denotes By looking at the clinical samples, a large body of data suggests impaired IFN signaling in severe and critically ill COVID-19 patients.
T225 1617-1848 Sentence denotes Blood analysis from across the studies reveals low or undetectable levels of IFN-β and IFN-λ levels in patients exhibiting severe disease symptoms or patients admitted to the ICU with in a critical condition (Hadjadj et al., 2020).
T226 1849-1988 Sentence denotes Of note, an elegant study was conducted to explore the functional role of IFN signaling during various stages of COVID-19 disease severity.
T227 1989-2133 Sentence denotes The study found robust impairment of IFN signaling in critically ill and severe patients in comparison to mild/moderate and healthy individuals.
T228 2134-2326 Sentence denotes IFN-β mRNA and protein were undetectable in all patients, whereas IFN-α2 protein was highly reduced in the plasma of severe and critically ill patients, corroborated with reduced IFN activity.
T229 2327-2541 Sentence denotes In line with the impaired IFN signaling, robust downregulation of some of the ISGs (MX1, IFITM1, IFIT2) observed in severe and critically ill patients suggest an overall reduced IFN response (Hadjadj et al., 2020).
T230 2542-2735 Sentence denotes Consistent with the low circulating levels of IFNs, transcriptional analysis of post-mortem lung samples further confirmed these observations and revealed no detectable type I or Type III IFNs.
T231 2736-2893 Sentence denotes Among the SARS-CoV-2 proteins which directly interfere with IFN response, ORF6, ORF8, and N protein inhibit IFN-β and NF-κB signaling (Li J.Y. et al., 2020).
T232 2894-3020 Sentence denotes Further, Konno et al. (2020) have identified a more extended variant of ORF3b with presumably more vigorous anti-IFN activity.
T233 3021-3137 Sentence denotes Thus, these early observations may point towards an impaired early IFN response by the host cells against SARS-CoV-2
T234 3138-3298 Sentence denotes Adding to the essential role of IFN in early antiviral response, two recent studies have shown that genetic changes are associated with inadequate IFN response.
T235 3299-3453 Sentence denotes In the first study, the presence of IFN neutralizing auto-antibodies found in patients who exhibited more severe disease condition (Bastard et al., 2020).
T236 3454-3574 Sentence denotes These auto-antibodies were more prevalent in men than women, that partly explains the susceptibility of men to COVID-19.
T237 3575-3645 Sentence denotes None of the asymptomatic or mild cases had detectable auto-antibodies.
T238 3646-3780 Sentence denotes In the other study, mutations in 13 key genes implicated in TLR3- and IRF7-dependent exhibit loss-of-function (Zhang Q. et al., 2020).
T239 3781-3935 Sentence denotes Patients or the cells derived from these patients with loss-of-function in these genes had inadequate IFN response and vulnerable to SARS-CoV-2 infection.
T240 3936-4111 Sentence denotes In a similar study on four patients with severe disease symptoms, the whole exome-sequencing revealed loss-of-function of TLR7, which is essentially involved in IFN signaling.
T241 4112-4252 Sentence denotes These patients exhibited decreased expression of IRF7, IFNB1, and ISG15, along with reduced production of IFN-γ (Van Der Made et al., 2020).
T242 4253-4579 Sentence denotes Thus, impaired IFN signaling, mediated either directly by the virus by interfering at various steps in the IFN signaling, or genetic predisposition of some individuals to inadequate IFN response and presence of IFN neutralizing auto-antibodies are some of the significant factors which determine the COVID-19 disease severity.
T243 4580-4784 Sentence denotes The dysfunctional IFN response in conjunction with other innate and adaptive immune responses may thus decide the path to recovery or progression to more severe form of the disease (Hadjadj et al., 2020).
T244 4785-4935 Sentence denotes Impaired type I interferon activity and exacerbated inflammatory responses in severe COVID-19 patients (Hadjadj et al., 2020; Park and Iwasaki, 2020).
T245 4936-5111 Sentence denotes A comprehensive understanding of the molecular mechanisms by which SARS-CoV-2 causes impaired IFN response is still lacking, and future studies may help us to understand this.
T246 5112-5290 Sentence denotes Nevertheless, these initial reports, along with the previous findings on SARS-CoV, are the basis behind exploring the therapeutic efficacy of IFN treatment for COVID-19 patients.
T247 5291-5440 Sentence denotes Currently, there are ongoing clinical trials with IFN-β1a (NCT04350671), which is in phase II, and IFN-l (NCT04388709) for the treatment of COVID-19.
T248 5441-5546 Sentence denotes The preliminary results with these drugs have been encouraging as of now (Davoudi-Monfared et al., 2020).