The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?

McKechnie, Julia L.; Blish, Catherine A.

doi:10.1016/j.chom.2020.05.009

Cited by 206 publications

(208 citation statements)

References 38 publications

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“…Lymphocytes play a crucial role in virus clearance after a viral infection. On the one hand, natural killer (NK) cells eliminate virally infected cells via degranulation, receptor-mediated apoptosis, and antibody-dependent cell-mediated cytotoxicity [56]. On the other hand, the humoral immune response, primarily mediated by the production of antibodies by plasma B cells (B lymphocyte-derived cells), plays a role in the neutralization of the virus [57].…”

Section: Discussionmentioning

confidence: 99%

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Delgado‐Enciso

Paz-Garcia²,

Barajas-Saucedo

et al. 2020

Preprint

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Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19.Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19.Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En

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Section: Discussionmentioning

confidence: 99%

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Delgado‐Enciso

Paz-Garcia²,

Barajas-Saucedo

et al. 2020

Preprint

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“…Such HLA-DR downregulation was also shown to immediately precede progression to severe respiratory failure [ 15 ]. On the other hand, monocytes are important players in inflammation, which is an integral part of COVID-19 [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Paračková

Zentsová

Bloomfield

et al. 2020

Cells

128

145

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COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host–pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.

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“…Compared to both healthy controls and patients with viral or bacterial pneumonia, COVID-19 patients, especially severe cases, have in their peripheral blood reduced numbers of CD14+CD16-DR+ "classical" monocytes, which may be due to the increased levels of IL-6 and/or dysregulated myelopoiesis (1,(66)(67)(68)(69)(70)(71). In the BAL, patients with severe COVID-19 have more macrophages than mild cases or healthy controls, and the increased macrophage numbers appear to be due to the presence of recruited monocyte-derived inflammatory macrophages (17,(72)(73)(74).…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice

Karhadkar

Pilling

Gomer

2020

Preprint

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SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. In this report, we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1β, IL-6, IL-12p70, IL-23, and IL-27 in serum. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms as well as diseases that generate a cytokine storm.

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The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?

Cited by 206 publications

References 38 publications

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness

Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice

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