Mechanisms and potential therapeutic targets of hyperinflammatory responses in SARS-CoV-2

Chukwuma, Ifeoma Felicia; Apeh, Victor Onukwube; Chiletugo, Okwesili Fred

doi:10.4149/av_2021_102

Cited by 7 publications

(11 citation statements)

References 26 publications

(77 reference statements)

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“…While the etiology of COVID-19-related ARDS is still not understood well, a growing body of evidence suggests that the hyperinflammation seen in COVID-19 ARDS patients is mediated via viral sepsis and kidney, cardiac, and epithelial dysfunction [ 30 , 31 ]. In the general population, ARDS may also be caused by respiratory infections, such as H5N1 avian influenza, or have non-pulmonary pathogenesis, such as septic bacteremia or major trauma [ 32–34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Though patients with COVID-19-related ARDS and the general population may have different mechanisms of ARDS onset, the results observed in this meta-analysis suggest that the underlying mechanism of onset may not influence important clinical outcomes like mortality. Interestingly, the respiratory failure and pulmonary edema seen in ARDS is, by definition, non-cardiogenic [ 35 ], yet it seems likely that COVID-19-related ARDS involves cardiac injury and dysfunction (among other organ systems) [ 30 , 31 ]. Such an acknowledgment highlights that, in order to better understand the mechanism of severe COVID-19 progression and the etiology of ARDS in these patients, we must be continually aware of and vigilant to the complex interplay that occurs between organ systems.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

Dmytriw

Chibbar

Chen

et al. 2021

Expert Review of Respiratory Medicine

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Introduction Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads to mortality. Outcomes of patients with COVID-19-related ARDS compared to ARDS unrelated to COVID-19 is not well characterized. Areas covered We performed a systematic review of PubMed, Scopus, and MedRxiv 11/1/2019 to 3/1/2021, including studies comparing outcomes in COVID-19-related ARDS (COVID-19 group) and ARDS unrelated to COVID-19 (ARDS group). Outcomes investigated were duration of mechanical ventilation-free days, intensive care unit (ICU) length-of-stay (LOS), hospital LOS, and mortality. Random effects models were fit for each outcome measure. Effect sizes were reported as pooled median differences of medians (MDMs), mean differences (MDs), or odds ratios (ORs). Expert opinion Ten studies with 2,281 patients met inclusion criteria (COVID-19: 861 [37.7%], ARDS: 1420 [62.3%]). There were no significant differences between the COVID-19 and ARDS groups for median number of mechanical ventilator-free days (MDM: −7.0 [95% CI: −14.8; 0.7], p = 0.075), ICU LOS (MD: 3.1 [95% CI: −5.9; 12.1], p = 0.501), hospital LOS (MD: 2.5 [95% CI: −5.6; 10.7], p = 0.542), or all-cause mortality (OR: 1.25 [95% CI: 0.78; 1.99], p = 0.361). Compared to the general ARDS population, results did not suggest worse outcomes in COVID-19-related ARDS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

Dmytriw

Chibbar

Chen

et al. 2021

Expert Review of Respiratory Medicine

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“…Given that accumulating evidence suggests that SARS-CoV2 is associated with a hyperinflammation condition characterized by excessive release of pro-inflammatory cytokines, anti-viral agents alone will not provide the much required therapeutic effect [ 23 ]. Hence, the need to combine anti-inflammatory agents such as interferons, ACE2 inhibitors, IL-6, and Janus kinase (JAK) family inhibitors, anticoagulants and other agents involved in inflammation resolution needs to conjointly examine the inflammatory status in these patients by measuring inflammatory markers such as IL-6 or LDH [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction of ACEI antihypertensive agent's administration with the inflammatory status at admission concerning COVID-19 clinical stay outcomes

Martínez-Urbistondo

Moreno-Torres

Mora-Vargas

et al. 2022

Vascular Pharmacology

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Interactions between anti-hypertensive agents (ACEI), comorbidities, inflammation, and stress status may impact hospital stay duration in COVID-19 patients. This retrospective study analyzed epidemiological data, comorbidities, metabolic/inflammatory markers, and clinical information from 165 SARS-CoV-2 positive patients. In a multiple linear regression model, an IL-6 higher than 100 mg/L, glucose at admission (baseline levels at the hospital entry), and the interaction between ACEI administration and LDH predicted the days of hospital admission (P < 0.001). In conclusion, hypertensive patients suffering more severe inflammatory condition assessed by LDH levels clinically benefited more and reduced the hospital stay when prescribed ACEI agents than those with lower systemic baseline inflammation at admission.

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“…SARS-CoV-2 has developed multiple mechanisms to avert the immune response of the host to survive, replicate, and cause COVID-19 disease. The immune evasion strategy starts with the downregulation of PRR activation and antagonizing its action through the formation of membrane-bound vesicles (Chukwuma et al, 2021;Li et al, 2020b). This is achieved by modification of viral RNA to resemble host mRNA through guanosine-capping and methylation by nonstructural proteins (nsps) (Vabret et al, 2020).…”

Section: Immune Evasionmentioning

confidence: 99%

“…It is worth noting that inflammaging, increase inflammatory response through deregulation of innate and adaptive immunity is the leading cause of cytokine storm, which is the major cause of death in patients (Muller et al, 2020;Chukwuma et al, 2021). This is attributed in part to the age-related loss of the naïve cell population which helps to avert the harmful effects of the over-stimulated inflammatory response (Marquez et al, 2020).…”

Section: Agementioning

confidence: 99%

Cross Talk on SARS-CoV-2 and Human Immunity

Chukwuma¹,

Apeh²,

Emaimo³

2021

njpr

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19) is now the leading cause of death globally. This review elaborated the human immune response to SARSCoV-2 and its immune evasion mechanisms as well as factors that determine the case fatality rate and effective immunity using articles selected from PubMed, Medline, Google Scholar and Science Direct that provided an in-depth knowledge of the immunopathogenesis of SARS-CoV-2. Findings from the forty eligible reviewed articles revealed that the host-viral interaction to SARS-CoV-2 involves the recognition of SARS-CoV-2, recruitment of adaptor proteins and antigen presentation which activates both innate and adaptive immunity involved in inhibition of viral replication (interferons), destruction of virus-infected cells (natural killer cells and CD8 cells) and viral clearance. However, SARS-CoV-2 subverts human immunity using multiple strategies such as production of double membrane vesicles, repression of adaptor proteins, interferons and antigen presentation. Accumulating shreds of evidence have shown that several factors such as age, sex, comorbidities, obesity, and lifestyle factors affect immune responsiveness to SARS-CoV-2. Hence, better knowledge of the viral interactions with the host and factors determining prevalence and severity is fundamental to the management and development of effective and biocompatible prophylactic and therapeutic options.

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Mechanisms and potential therapeutic targets of hyperinflammatory responses in SARS-CoV-2

Abstract: Mechanisms and potential therapeutic targets of hyperinflammatory responses in SARS-CoV2 Ifeoma felIcIa chukwuma 1 , VIctor onukwube apeh 1 , okwesIlIeze frederIck c. nwodo 2

Cited by 7 publications

References 26 publications

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

Interaction of ACEI antihypertensive agent's administration with the inflammatory status at admission concerning COVID-19 clinical stay outcomes

Cross Talk on SARS-CoV-2 and Human Immunity

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