Immune suppression in the early stage of COVID-19 disease

Abstract

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

“…The time between sample collection and clinical presentation varied among patients and among groups. Our findings may thus be biased, especially because of the known stage-dependent immune alterations of COVID-19 ( Mann et al., 2020 ; Tian et al., 2020 ). Finally, neurological signs and symptoms in Neuro-COVID might not only depend on the observed CSF changes, but also on systemic factors, such as oxygen or serum cytokine levels.…”

“…Studies with longitudinal clinical follow-up will be required to address this question. Additionally, the effects of immune responses may be stage-specific in Neuro-COVID as observed in the multi-stage kinetics in pulmonary COVID-19 ( Mann et al., 2020 ; Tian et al., 2020 ).…”

SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO

“…The infection of SARS-CoV-2 and progression of COVID-19 exhibit a ''two-stage'' pattern. During the early stage, mild or asymptomatic COVID-19 patients undergo immunosuppression, which facilitates significant viral shedding and transmission (Tian et al, 2020). Because ORF9b has emerged as a potent IFN antagonist during the early stage of SARS-CoV-2 infection, it is convincible that SARS-CoV-2 uses the early protein ORF9b to mask the antiviral defense and inflammatory response in earlystage patients.…”

Intersection between ageing-related Genes and SARS-CoV-2 Interactome: Is it higher than expected?

“…Therefore, the dysregulation may cause the accumulation on DNA damage or on the protein levels accumulating errors in the downstream cascade of mechanisms [59]. The role of EEF2 in severe cases of COVID-19 has also been elucidated in [51]. Thus our study provides another evidence.…”

“…Moreover, elderly accumulate inflammatory mediators in tissues (inflammageing process), that may occur by the accumulation of DNA lesions that in turn, trigger the increased production of inflammatory mediators [50]. In parallel, the link between COVID-19 and the suppression of the immune system has been observed in [51]. Authors found that many proteins related to the immune response were modulated, causing the possible suppression of such a system.…”