Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators

Yasmeen, Nusrath; Harikrishnan, Sivadasanpillai; Lakhawat, Sudarshan Singh; Datta, Manali; Sharma, Pushpender Kumar; Jain, Ajay; Khanna, Rakhi; Jayalakshmi, S; Kumar, Vikram

doi:10.1016/j.bcp.2023.115437

Cited by 5 publications

(5 citation statements)

References 336 publications

(376 reference statements)

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“…Both statins 26,27 and drugs modulating eicosanoid formation or action may be of benefit in preventing or treating COVID‐19 28–30 . However, none, to date, including aspirin, has been validated by randomised control trials 31 .…”

Section: Introductionmentioning

confidence: 99%

“…Both statins 26,27 and drugs modulating eicosanoid formation or action may be of benefit in preventing or treating COVID-19. [28][29][30] However, none, to date, including aspirin, has been validated by randomised control trials. 31 Despite early concerns, treatment with other non-steroidal antiinflammatory drugs does not appear to affect adversely the clinical course of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

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BackgroundLipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU).MethodsMass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity.ResultsCirculating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity.ConclusionsA broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Meng,

Sengupta,

Ricciotti

et al. 2023

Clinical & Translational Med

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“…However, levels of many variables remained altered, worsening during ICU stay (i.e., D-dimer, GGT, GPT), underscoring the complexity of the clinical situation of these patients. Over-exuberant in ammatory response and dysregulated host immune system are common ndings in severe cases of COVID-19 25 . Among other effects, in ammatory processes lead to oxidative stress and altered levels of different trace elements in serum 26 .…”

Section: Discussionmentioning

confidence: 99%

Changes in trace elements and metallothioneins levels and their relationship with clinical, biochemical, and inflammatory parameters in patients with COVID-19 during the early ICU phase

Herrera-Quintana

Vázquez-Lorente

Gamarra-Morales

et al. 2023

Preprint

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Background The levels of trace elements and Metallothioneins (MTs) could play a key role in modulating the inflammatory reaction and pathogenesis of COVID-19. Their effects on clinical variables are of interest for the characterization and management of this disease. Thus, the present study aimed to investigate the association between circulating Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn), and MTs levels, as well as their relationship with clinical, biochemical, and inflammatory parameters in critical care patients with COVID-19 at early Intensive Care Unit (ICU) phase. Methods A total of 86 critically ill patients with COVID-19 were monitored from the first day of admission to the ICU until the third day of stay. Clinical parameters were retrieved from the hospital database. Biochemical and inflammatory parameters were analyzed following enzymatic colorimetry and immunoassay procedures. Serum samples were used to assess mineral levels by inductively coupled plasma-mass spectrometry and MTs levels by differential pulse voltammetric. Results Levels of Cu and MTs decreased (all P ≤ 0.046) after 3 days of ICU stay, increasing the prevalence of Cu deficient values from 50–65.3% (P = 0.015) on the third day of ICU stay. Fe and Zn were shown to have a predictive value for mortality and severity. Changes in Fe were directly related to changes in Cu and Mn (all r ≥ 0.266; P ≤ 0.019). In contrast, changes in MTs were inversely related to changes in Mn and albumin (all r≥–0.255; P ≤ 0.039). Conclusions The present study indicated a risk of trace element deficiencies related to different biochemical and clinical parameters. We suggest monitoring the mineral status and performing nutritional interventions, when appropriate, that could help to improve the altered parameters, such as inflammatory conditions and, thus, the prognosis in critically ill patients with COVID-19.

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“…However, levels of many variables remained altered, worsening during ICU stay (i.e., D-dimer, GGT, GPT), underscoring the complexity of the clinical situation of these patients. An over-exuberant inflammatory response and dysregulated host immune system are common findings in severe cases of COVID-19 [ 27 ]. Among other effects, inflammatory processes lead to oxidative stress and altered levels of different trace elements in serum [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Evolution of Status of Trace Elements and Metallothioneins in Patients with COVID-19: Relationship with Clinical, Biochemical, and Inflammatory Parameters

et al. 2023

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The inflammatory reaction and pathogenesis of COVID-19 may be modulated by circulating trace elements (Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn)) and Metallothioneins (MTs). Thus, the present study aimed to investigate their relationship with clinical, biochemical, and inflammatory parameters in patients with COVID-19 at the early Intensive Care Unit (ICU) phase. Critically ill patients (n = 86) were monitored from the first day of ICU admission until the third day of stay. Serum samples were used to assess mineral levels via Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and MT levels via differential pulse voltammetry. Levels of Cu and MTs were significantly decreased after 3 days (p < 0.05), increasing the prevalence of Cu-deficient values from 50% to 65.3% (p = 0.015). Fe and Zn were shown to have a predictive value for mortality and severity. The present study suggests trace element deficiency may be a risk factor during early ICU treatment of COVID-19, as it is related to different biochemical and clinical parameters, indicating a possible beneficial effect of restoring proper levels of these micronutrients.

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Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators

Cited by 5 publications

References 336 publications

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

Changes in trace elements and metallothioneins levels and their relationship with clinical, biochemical, and inflammatory parameters in patients with COVID-19 during the early ICU phase

Evolution of Status of Trace Elements and Metallothioneins in Patients with COVID-19: Relationship with Clinical, Biochemical, and Inflammatory Parameters

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