Is innate immunity our best weapon for flattening the curve?

Angka, Leonard; Market, Marisa; Ardolino, Michele; Auer, Rebecca C.

doi:10.1172/jci140530

Cited by 13 publications

(15 citation statements)

References 23 publications

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“…Innate immunity plays an important role in initial control and the pathogenesis of COVID-19. Indeed, there are a number of clinical trials focused on the use of interferon and anti-inflammatory agents to counteract the sometimes deleterious immune response to SARS-CoV-2 infection (Angka et al, 2020). Such an approach could be key in treating severe cases of COVID-19, which correlate with cytokine storm and hyper-activation of immune responses normally not related to viral infections, particularly type-2 effectors (Lucas et al 2020).…”

Section: Discussionmentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

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The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis.

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Section: Discussionmentioning

confidence: 99%

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Thépaut

Luczkowiak

Vivès

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…There is a justified concern that suboptimal vaccine efficacy for at-risk populations and the elderly could place the goal of not having to achieve herd immunity first in jeopardy. At the same time, a non-efficacious vaccine for at-risk populations could increase the probability of second and subsequent waves of infection in these populations (7).…”

Section: Introductionmentioning

confidence: 99%

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

et al. 2020

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The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."

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“…For innate immunity, the pathogen associated molecular patterns (PAMPs) on the pathogen’s surface bind with the pattern recognition receptors (PRRs, including TLRs, Toll-like receptors) on macrophages and dendritic cells and in the process interferons (IFNs) and interleukins (ILs) are released, dendritic cells are activated and cytotoxic T cells and NK cells are enhanced which help in getting rid of the viruses [14] , [15] . It has been suggested that trained immunity (memory in innate immunity from antigen challenge) in children may provide them a strong innate immunity [14] , [15] , [16] . Against this backdrop, immunotherapy in the form of immune boosting through BCG vaccination is also under clinical trial [14] , [15] , [16] .…”

mentioning

confidence: 99%

“…It has been suggested that trained immunity (memory in innate immunity from antigen challenge) in children may provide them a strong innate immunity [14] , [15] , [16] . Against this backdrop, immunotherapy in the form of immune boosting through BCG vaccination is also under clinical trial [14] , [15] , [16] .…”

mentioning

confidence: 99%

Repurposing prolactin as a promising immunomodulator for the treatment of COVID-19: Are common Antiemetics the wonder drug to fight coronavirus?

Sen¹

2020

Medical Hypotheses

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Prolactin (PRL), the well-known lactogenic hormone, plays a crucial role in immune function given the fact that long term hypoprolactinemia (serum prolactin level below normal) can even lead to death from opportunistic infection. High blood PRL level is known to provide an immunological advantage in many pathological conditions (with some exceptions like autoimmune diseases) and women, because of their higher blood PRL level, get an advantage in this regard. It has been reported that by controlled enhancement of blood PRL level (within the physiological limit and in some cases a little elevated above the normal to induce mild hyperprolactinemia) using dopamine antagonists such immune-stimulatory advantage can led to survival of the patients in many critical conditions. Here it is hypothesized that through controlled augmentation of blood PRL level using dopamine antagonists like domperidone/metoclopramide, which are commonly used drugs for the treatment of nausea and vomiting, both innate and adaptive immunity can be boosted to evade or tone down COVID-19. The hypothesis is strengthened from the fact that at least seven little-understood salient observations in coronavirus patients can apparently be explained by considering the role of enhanced PRL in line with the proposed hypothesis and hence, clinical trials (both therapeutic and prophylactic) on the role of enhanced PRL on the course and outcome of coronavirus patients should be conducted accordingly.

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Is innate immunity our best weapon for flattening the curve?

Cited by 13 publications

References 23 publications

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

Repurposing prolactin as a promising immunomodulator for the treatment of COVID-19: Are common Antiemetics the wonder drug to fight coronavirus?

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