Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

Shafqat, Areez; Shafqat, Shameel; Salameh, Sulaiman Al; Kashir, Junaid; Alkattan, Khaled; Yaqinuddin, Ahmed

doi:10.3389/fimmu.2022.835104

Cited by 31 publications

(24 citation statements)

References 284 publications

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“…Furthermore, it was noted that key alterations in peripheral blood circulating B cell populations during the acute phase of SARS-CoV-2 infection were linked to the decreased levels of the relative and absolute number of B cells, increased frequencies of plasma cell precursors, atypical CD21-negative and activated B cells etc. [49,51,52]. Currently, we have shown that vitamin D supplementation could effectively decrease the relative numbers of activated CD38++CD27 transitional B cells and 'naïve' B cells in patients with acute COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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“…Alternatively, consolidations can represent ischemic regions. This overlap of viral, inflammatory, immune, and vascular events is clinically expressed by disease phenotypes with different prognostic weight [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Lung Ultrasound in SARS-CoV-19 Pneumonia Management

Lugarà¹,

Tamburrini²,

Coppola³

et al. 2022

Diagnostics

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Purpose: We aimed to assess the role of lung ultrasound (LUS) in the diagnosis and prognosis of SARS-CoV-2 pneumonia, by comparing it with High Resolution Computed Tomography (HRCT). Patients and methods: All consecutive patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in COVID Centers were enrolled. LUS and HRCT were carried out on all patients by expert operators within 48–72 h of admission. A four-level scoring system computed in 12 regions of the chest was used to categorize the ultrasound imaging, from 0 (absence of visible alterations with ultrasound) to 3 (large consolidation and cobbled pleural line). Likewise, a semi-quantitative scoring system was used for HRCT to estimate pulmonary involvement, from 0 (no involvement) to 5 (>75% involvement for each lobe). The total CT score was the sum of the individual lobar scores and ranged from 0 to 25. LUS scans were evaluated according to a dedicated scoring system. CT scans were assessed for typical findings of COVID-19 pneumonia (bilateral, multi-lobar lung infiltration, posterior peripheral ground glass opacities). Oxygen requirement and mortality were also recorded. Results: Ninety-nine patients were included in the study (male 68.7%, median age 71). 40.4% of patients required a Venturi mask and 25.3% required non-invasive ventilation (C-PAP/Bi-level). The overall mortality rate was 21.2% (median hospitalization 30 days). The median ultrasound thoracic score was 28 (IQR 20–36). For the CT evaluation, the mean score was 12.63 (SD 5.72), with most of the patients having LUS scores of 2 (59.6%). The bivariate correlation analysis displayed statistically significant and high positive correlations between both the CT and composite LUS scores and ventilation, lactates, COVID-19 phenotype, tachycardia, dyspnea, and mortality. Moreover, the most relevant and clinically important inverse proportionality in terms of P/F, i.e., a decrease in P/F levels, was indicative of higher LUS/CT scores. Inverse proportionality P/F levels and LUS and TC scores were evaluated by univariate analysis, with a P/F–TC score correlation coefficient of −0.762, p < 0.001, and a P/F–LUS score correlation coefficient of −0.689, p < 0.001. Conclusions: LUS and HRCT show a synergistic role in the diagnosis and disease severity evaluation of COVID-19.

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“…Severe COVID-19 also features dysregulated neutrophil responses with increased NET production, contributing to the systemic inflammatory response syndrome and immunothrombosis in these patients ( 136 , 137 ). DM patients are known to be predisposed to severe COVID-19.…”

Section: Metformin and Netsmentioning

confidence: 99%

Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus

et al. 2022

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Immune dysfunction is widely regarded as one of the central tenants underpinning the pathophysiology of diabetes mellitus (DM) and its complications. When discussing immunity, the role of neutrophils must be accounted for: neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation, where they contribute to host defense via phagocytosis, degranulation, and extrusion of neutrophil extracellular traps (NETs). NETs are composed of DNA associated with nuclear and cytosolic neutrophil proteins. Although originally reported as an antimicrobial strategy to prevent microbial dissemination, a growing body of evidence has implicated NETs in the pathophysiology of various autoimmune and metabolic disorders. In these disorders, NETs propagate a pathologic inflammatory response with consequent tissue injury and thrombosis. Many diabetic complications—such as stroke, retinopathy, impaired wound healing, and coronary artery disease—involve these mechanisms. Therefore, in this review, we discuss laboratory and clinical data informing our understanding of the role of NETs in the development of these complications. NET markers, including myeloperoxidase, citrullinated histone H3, neutrophil elastase, and cell-free double-stranded DNA, can easily be measured in serum or be detected via immunohistochemical/immunocytochemical staining of tissue specimens. Therefore, NET constituents potentially constitute reliable biomarkers for use in the management of diabetic patients. However, no NET-targeting drug is currently approved for the treatment of diabetic complications; a candidate drug will require the outcomes of well-designed, robust clinical trials assessing whether NET inhibition can benefit patients in terms of morbidity, quality of life, health expenditures, and mortality. Therefore, much work remains to be done in translating these encouraging pieces of data into clinical trials for NET-targeting medications to be used in the clinic.

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Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

Cited by 31 publications

References 284 publications

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

The Role of Lung Ultrasound in SARS-CoV-19 Pneumonia Management

Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus

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