Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19

Lega, Sara; Naviglio, Samuele; Volpi, Stefano; Tommasini, Alberto

doi:10.3390/vaccines8020224

Cited by 52 publications

(70 citation statements)

References 216 publications

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“…An initial viral evasion from innate immunity affects the course of the disease tremendously. 3,21 The N protein can also serve as an important diagnostic marker for coronavirus disease and a major immunogen by priming protective immune responses. The recent mass spectrometry (MS) -based studies of SARS-CoV-2 proteins from gargle solution samples and nasal swab samples of COVID-19 patients detected the presence of N protein peptides, making them a potential diagnostic biomarker for COVID-19.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Supekar

Shajahan

Gleinich

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19) started at the end of 2019 in Wuhan, China has spread rapidly and became a pandemic. Since there is no therapy available that is proven as fully protective against COVID-19, a vaccine to protect against deadly COVID-19 is urgently needed. Nucleocapsid protein (N protein), is one of the most abundant proteins in coronaviruses and is a potential target for both vaccine development and point of care diagnostics. The variable mass of N protein (45 to 60 kDa), suggests the presence of post-translational modifications (PTMs), and it is critical to clearly define these PTMs to gain the structural understanding necessary for further vaccine research. There have been several reports suggesting that the N protein is phosphorylated but lacks glycosylation. Our comprehensive glycomics and glycoproteomics experiments confirm that the N protein is highly O-glycosylated and also contains significant levels of N-glycosylation. We were able to confirm the presence of O-glycans on seven sites with substantial glycan occupancy, in addition to less abundant O-glycans on four sites. We also detected N-glycans on two out of five potential N-glycosylation sites. Moreover, we were able to confirm one phosphorylation site. Recent studies have indicated that the N protein can serve as an important diagnostic marker for coronavirus disease and a major immunogen by priming protective immune responses. Thus, detailed structural characterization of the N protein may provide useful insights for understanding the roles of glycosylation on viral pathogenesis and also in vaccine design and development.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Supekar

Shajahan

Gleinich

et al. 2020

Preprint

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“…As expected, ICU patients were hospitalized for longer periods. Median serum levels of several pro-inflammatory biomarkers, such as LDH, dimer-D and IL-6, were significantly higher in ICU patients than in non-ICU patients, further confirming their association with COVID-19 severity [2][3][4][5]. In contrast, the median total lymphocyte counts did not differ across comparison groups (Table 1).…”

Section: Clinical Characteristics Of Covid-19 Patientsmentioning

confidence: 68%

“…The copyright holder for this preprint this version posted July 24, 2020. ; https://doi.org/10.1101/2020.07. 22 progressive disease and poor outcomes [4,5]. At most, we observed weak or very weak correlations between the antibody assays and these inflammatory biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…Here, in addition to further characterizing the antibody response to SARS-CoV-2 in hospitalized COVID-19 patients, we mainly aimed to determine whether a relationship could be established between the magnitude of SARS-CoV-2 RBD IgG and NtAb levels and the "inflammatory state" of patients, which has been shown to directly correlate with COVID-19 severity and prognosis [2][3][4][5].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical presentation of COVID-19 varies widely, ranging from asymptomatic to mild or severe forms [2,3]. Worse clinical outcomes are related to an imbalanced immune response skewed toward a Th 1 pro-inflammatory profile, which leads to the uncontrolled release of cytokines and chemokines, such as interleukin-6 (IL-6), that mediates progression into acute respiratory distress syndrome, multiorgan failure, and death [4,5].…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 Patients

Gozalbo-Rovira

Giménez

Latorre

et al. 2020

Preprint

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Background: The involvement of SARS-CoV-2 antibodies in mediating immunopathogenetic events in COVID-19 patients has been suggested. By using several experimental approaches, we investigated the potential association between SARS-CoV-2 IgGs recognizing the spike (S) protein receptor-binding domain (RBD), neutralizing antibodies (NtAb) targeting S, and COVID-19 severity. Patients and Methods: This unicenter, retrospective, observational study included 51 hospitalized patients (24 at the intensive care unit; ICU). A total of 93 sera from these patients collected at different time points from the onset of symptoms were analyzed. SARS-CoV-2 RBD IgGs were quantitated by ELISA and NtAb50 titers were measured in a GFP reporter-based pseudotyped virus platform. Demographic and clinical data, complete blood counts, as well as serum levels of ferritin, Dimer-D, C reactive protein (CRP), lactose dehydrogenase (LDH), and interleukin-6 (IL-6) were retrieved from clinical charts. Results: The overall correlation between levels of both antibody measurements was good (Rho=0.79; P=0<0.001). SARS-CoV-2 RBD IgG and NtAb50 levels in sera collected up to day 30 after the onset of symptoms were comparable between ICU and non-ICU patients (P=>0.1). The percentage of patients who exhibited high NtAb50 titers (≥160) was similar (P=0.20) in ICU (79%) and non-ICU (60%) patients. Four ICU patients died; two of these achieved NtAb50 titers ≥1/160 while the other two exhibited a 1/80 titer. Very weak (Rho=>0.0-<0.2) or weak (Rho=>0.2-<0.4) correlations were observed between anti-RBD IgGs, NtAb50, and serum levels pro-inflammatory biomarkers. Conclusions: The data presented herein do not support an association between SARS-CoV-2 RBD IgG or NtAb50 levels and COVID-19 severity

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Immunobiology and immunotherapy of COVID‐19: A clinically updated overview

Esmaeilzadeh

Elahi

2020

Journal Cellular Physiology

104

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new member of the coronavirus family that can cause coronavirus disease 2019 (COVID‐19). COVID‐9 has become a global pandemic with severe health issues around the world. Identifying the accurate immunopathogenesis of the COVID‐19 and the immune response against SARS‐CoV‐2 is necessary for the development of therapeutic approaches and rational drug design. This paper aims to overview the updated clinical data on the immunopathogenesis of the COVID‐19 and review the innate and adaptive immune response to SARS‐CoV‐2. Also, challenges of the immune response to SARS‐CoV‐2 leading to dysfunctional immune response and their contribution to the progression of the disease have been discussed. To achieve a more efficient immune response, multiple methods could be applied, including regulation of the immune response, augmentation of the immune system against the virus, inhibition of the dysfunctional immune checkpoints, and inhibition of the viral replication/infection. Based on the immune response against SARS‐CoV‐2 and its dysfunction, we introduce potential immunotherapies as well as reviewing recruiting/completed clinical trials of COVID‐19.

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Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19

Cited by 52 publications

References 216 publications

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 Patients

Immunobiology and immunotherapy of COVID‐19: A clinically updated overview

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