[go: up one dir, main page]

 
 
Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (2,243)

Search Parameters:
Keywords = D-InSAR

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
21 pages, 23870 KiB  
Article
Utilizing LuTan-1 SAR Images to Monitor the Mining-Induced Subsidence and Comparative Analysis with Sentinel-1
by Fengqi Yang, Xianlin Shi, Keren Dai, Wenlong Zhang, Shuai Yang, Jing Han, Ningling Wen, Jin Deng, Tao Li, Yuan Yao and Rui Zhang
Remote Sens. 2024, 16(22), 4281; https://doi.org/10.3390/rs16224281 (registering DOI) - 17 Nov 2024
Viewed by 141
Abstract
The LuTan-1 (LT-1) satellite, launched in 2022, is China’s first L-band full-polarimetric Synthetic Aperture Radar (SAR) constellation, boasting interferometry capabilities. However, given its limited use in subsidence monitoring to date, a comprehensive evaluation of LT-1’s interferometric quality and capabilities is necessary. In this [...] Read more.
The LuTan-1 (LT-1) satellite, launched in 2022, is China’s first L-band full-polarimetric Synthetic Aperture Radar (SAR) constellation, boasting interferometry capabilities. However, given its limited use in subsidence monitoring to date, a comprehensive evaluation of LT-1’s interferometric quality and capabilities is necessary. In this study, we utilized the Differential Interferometric Synthetic Aperture Radar (DInSAR) technique to analyze mining-induced subsidence results near Shenmu City (China) with LT-1 data, revealing nine subsidence areas with a maximum subsidence of −19.6 mm within 32 days. Furthermore, a comparative analysis between LT-1 and Sentinel-1 data was conducted focusing on the aspects of subsidence results, interferometric phase, scattering intensity, and interferometric coherence. Notably, LT-1 detected some subsidence areas larger than those identified by Sentinel-1, attributed to LT-1’s high resolution, which significantly enhances the detectability of deformation gradients. Additionally, the coherence of LT-1 data exceeded that of Sentinel-1 due to LT-1’s L-band long wavelength compared to Sentinel-1’s C-band. This higher coherence facilitated more accurate capturing of differential interferometric phases, particularly in areas with large-gradient subsidence. Moreover, the quality of LT-1’s monitoring results surpassed that of Sentinel-1 in root mean square error (RMSE), standard deviation (SD), and signal-to-noise ratio (SNR). In conclusion, these findings provide valuable insights for future subsidence-monitoring tasks utilizing LT-1 data. Ultimately, the systematic differences between LT-1 and Sentinel-1 satellites confirm that LT-1 is well-suited for detailed and accurate subsidence monitoring in complex environments. Full article
(This article belongs to the Special Issue Advances in Remote Sensing for Land Subsidence Monitoring)
Show Figures

Figure 1

Figure 1
<p>(<b>a</b>) Geographical location of the study area; (<b>b</b>) desert grass beach area; (<b>c</b>) open-pit mining area.</p>
Full article ">Figure 2
<p>Technical workflow chart.</p>
Full article ">Figure 3
<p>(<b>a</b>) LT-1 satellite data subsidence monitoring results in the study area; (<b>b</b>–<b>d</b>) enlarged views of typical subsidence areas; (<b>c1</b>,<b>d1</b>) are typical subsidence areas identified by both LT-1 and Sentinel-1 satellite data.</p>
Full article ">Figure 4
<p>(<b>a</b>) Sentinel-1 satellite data subsidence monitoring results in the study area; (<b>b</b>–<b>d</b>) enlarged views of typical subsidence areas.</p>
Full article ">Figure 5
<p>(<b>a</b>,<b>d</b>,<b>g</b>,<b>j</b>) Results from LT-1 satellite data; (<b>b</b>,<b>e</b>,<b>h</b>,<b>k</b>) results from Sentinel-1 satellite data; (<b>c</b>,<b>f</b>,<b>i</b>,<b>l</b>) Google Earth optical images. The dashed circles are areas of subsidence, the AA′ is profile line.</p>
Full article ">Figure 6
<p>Subsidence results along the A-A′ cross-section for LT-1 and Sentinel-1.</p>
Full article ">Figure 7
<p>(<b>d</b>,<b>e</b>) Interferometric phase maps of LT-1 and Sentinel-1 satellite data, respectively; (<b>a</b>–<b>c</b>) enlarged views of LT-1 satellite data, Sentinel-1 satellite data, and Google optical images in the first typical subsidence area; (<b>f</b>–<b>h</b>) the same for the second typical subsidence area. The dashed circles are areas of subsidence.</p>
Full article ">Figure 8
<p>(<b>d</b>,<b>e</b>) Backscatter intensity maps of LT-1 and Sentinel-1 satellite data, respectively; (<b>a</b>–<b>c</b>,<b>f</b>–<b>h</b>) enlarged views of LT-1 satellite data, Sentinel-1 satellite data, and Google optical images.</p>
Full article ">Figure 9
<p>(<b>d</b>,<b>e</b>) Coherence maps of LT-1 and Sentinel-1, respectively; (<b>a</b>–<b>c</b>,<b>f</b>–<b>h</b>) enlarged views of LT-1, Sentinel-1, and Google optical images in the typical subsidence areas A and B, respectively.</p>
Full article ">Figure 10
<p>(<b>a</b>–<b>c</b>) Statistical chart of coherence comparison in the study area, area A, and area B.</p>
Full article ">Figure 11
<p>The track of the LT-1 satellite observing the study area is shown in the left image, while the track of the Sentinel-1 satellite observing the study area is depicted in the right image.</p>
Full article ">Figure 12
<p>MDDG distribution from different SAR satellites under the variations of wavelength and resolution.</p>
Full article ">
21 pages, 18859 KiB  
Article
Polarisation Synthesis Applied to 3D Polarimetric Imaging for Enhanced Buried Object Detection and Identification
by Samuel J. I. Forster, Anthony J. Peyton, Frank J. W. Podd and Nigel Davidson
Remote Sens. 2024, 16(22), 4279; https://doi.org/10.3390/rs16224279 (registering DOI) - 17 Nov 2024
Viewed by 174
Abstract
Detecting sub-surface objects poses significant challenges, partly due to attenuation of the ground medium and cluttered environments. The acquisition polarisation and antenna orientation can also yield significant variation of detection performance. These challenges can be mitigated by developing more versatile systems and algorithms [...] Read more.
Detecting sub-surface objects poses significant challenges, partly due to attenuation of the ground medium and cluttered environments. The acquisition polarisation and antenna orientation can also yield significant variation of detection performance. These challenges can be mitigated by developing more versatile systems and algorithms to enhance detection and identification. In this study, a novel application of a 3D SAR inverse algorithm and polarisation synthesis was applied to ultra-wideband polarimetric data of buried objects. The principle of polarisation synthesis facilitates an adaptable technique which can be used to match the target’s polarisation characteristics, and the application of this revealed hidden structures, enhanced detection, and increased received power when compared to single polarisation results. This study emphasises the significance of polarimetry in ground-penetrating radar (GPR), particularly for target discrimination in high-lift-off applications. The findings offer valuable insights that could drive future research and enhance the performance of these sensing systems. Full article
(This article belongs to the Section Remote Sensing Image Processing)
Show Figures

Figure 1

Figure 1
<p>Imaging geometry in 3D.</p>
Full article ">Figure 2
<p>The polarisation ellipse shown with ellipticity angle <math display="inline"><semantics> <mi>χ</mi> </semantics></math>, orientation angle <math display="inline"><semantics> <mi>φ</mi> </semantics></math>, wave amplitudes <math display="inline"><semantics> <msub> <mi>A</mi> <mi>x</mi> </msub> </semantics></math> and <math display="inline"><semantics> <msub> <mi>A</mi> <mi>y</mi> </msub> </semantics></math>, and magnitude <span class="html-italic">A</span>.</p>
Full article ">Figure 3
<p>Experimental setup showing (<b>a</b>) the positioning system, VNA, and antenna and (<b>b</b>) close-up view of the dual-polarised antenna.</p>
Full article ">Figure 4
<p>The chosen targets in the study showing (<b>a</b>) 5 cm diameter metallic sphere, (<b>b</b>,<b>c</b>) a wire in two orientations, and (<b>d</b>) air-filled cylindrical container.</p>
Full article ">Figure 5
<p>Estimated received power versus range for a 5 cm diameter metallic sphere buried in sand for <math display="inline"><semantics> <mrow> <msub> <mi>σ</mi> <mrow> <mi>c</mi> <mi>o</mi> <mi>n</mi> <mi>d</mi> </mrow> </msub> <mo>=</mo> <msup> <mn>10</mn> <mrow> <mo>−</mo> <mn>3</mn> </mrow> </msup> </mrow> </semantics></math> and <math display="inline"><semantics> <msup> <mn>10</mn> <mrow> <mo>−</mo> <mn>5</mn> </mrow> </msup> </semantics></math> <math display="inline"><semantics> <mrow> <msup> <mi>Sm</mi> <mrow> <mo>−</mo> <mn>1</mn> </mrow> </msup> </mrow> </semantics></math>.</p>
Full article ">Figure 6
<p>SAR images of the metallic sphere with (<b>a</b>) HH; (<b>b</b>) HV; (<b>c</b>) VV polarisations.</p>
Full article ">Figure 7
<p>Comparison of sphere target cross-sections with (HH 1) and without (HH 2) refraction corrections, shown in (<b>a</b>) linear scale and (<b>b</b>) dB scale.</p>
Full article ">Figure 8
<p>SAR images of the straight insulated wire with (<b>a</b>) HH; (<b>b</b>) HV; (<b>c</b>) VV polarisations.</p>
Full article ">Figure 9
<p>SAR images of the curved insulated wire with (<b>a</b>) HH; (<b>b</b>) HV; (<b>c</b>) VV polarisations.</p>
Full article ">Figure 10
<p>SAR images of the air-filled cylinder with (<b>a</b>) HH; (<b>b</b>) HV; (<b>c</b>) VV polarisations.</p>
Full article ">Figure 11
<p>Orientation plot of the metallic sphere.</p>
Full article ">Figure 12
<p>Polarimetric images of the sphere synthesised in linear and circular polarisations. (<b>a</b>) Linear horizontal; (<b>b</b>) linear vertical; (<b>c</b>) linear +45°; (<b>d</b>) linear <math display="inline"><semantics> <mrow> <msup> <mrow> <mo>−</mo> <mn>45</mn> </mrow> <mo>°</mo> </msup> </mrow> </semantics></math>; (<b>e</b>) RHC; (<b>f</b>) LHC.</p>
Full article ">Figure 13
<p>Orientation plot of the insulated wire.</p>
Full article ">Figure 14
<p>Polarimetric images of the insulated wire synthesised in linear and circular polarisations. (<b>a</b>) Linear horizontal; (<b>b</b>) linear vertical; (<b>c</b>) linear +45°; (<b>d</b>) linear <math display="inline"><semantics> <mrow> <msup> <mrow> <mo>−</mo> <mn>45</mn> </mrow> <mo>°</mo> </msup> </mrow> </semantics></math>; (<b>e</b>) RHC; (<b>f</b>) LHC.</p>
Full article ">Figure 15
<p>Orientation plot of the curved insulated wire.</p>
Full article ">Figure 16
<p>Polarimetric images of the curved insulated wire synthesised in linear and circular polarisations. (<b>a</b>) Linear horizontal; (<b>b</b>) linear vertical; (<b>c</b>) linear +45°; (<b>d</b>) linear <math display="inline"><semantics> <mrow> <msup> <mrow> <mo>−</mo> <mn>45</mn> </mrow> <mo>°</mo> </msup> </mrow> </semantics></math>; (<b>e</b>) RHC; (<b>f</b>) LHC.</p>
Full article ">Figure 17
<p>Comparison of curved wire cross-sections for HH and RHC polarisations, shown in (<b>a</b>) linear scale and (<b>b</b>) dB scale.</p>
Full article ">Figure 18
<p>Histogram comparison for HH and RHC polarisations.</p>
Full article ">Figure 19
<p>Orientation plot of the air-filled cylinder.</p>
Full article ">Figure 20
<p>Polarimetric images of the air-filled cylinder synthesised in linear and circular polarisations. (<b>a</b>) Linear horizontal; (<b>b</b>) linear vertical; (<b>c</b>) linear +45°; (<b>d</b>) linear <math display="inline"><semantics> <mrow> <msup> <mrow> <mo>−</mo> <mn>45</mn> </mrow> <mo>°</mo> </msup> </mrow> </semantics></math>; (<b>e</b>) RHC; (<b>f</b>) LHC.</p>
Full article ">
17 pages, 6219 KiB  
Article
DGGNets: Deep Gradient-Guidance Networks for Speckle Noise Reduction
by Li Wang, Jinkai Li, Yi-Fei Pu, Hao Yin and Paul Liu
Fractal Fract. 2024, 8(11), 666; https://doi.org/10.3390/fractalfract8110666 (registering DOI) - 15 Nov 2024
Viewed by 182
Abstract
Speckle noise is a granular interference that degrades image quality in coherent imaging systems, including underwater sonar, Synthetic Aperture Radar (SAR), and medical ultrasound. This study aims to enhance speckle noise reduction through advanced deep learning techniques. We introduce the Deep Gradient-Guidance Network [...] Read more.
Speckle noise is a granular interference that degrades image quality in coherent imaging systems, including underwater sonar, Synthetic Aperture Radar (SAR), and medical ultrasound. This study aims to enhance speckle noise reduction through advanced deep learning techniques. We introduce the Deep Gradient-Guidance Network (DGGNet), which features an architecture comprising one encoder and two decoders—one dedicated to image recovery and the other to gradient preservation. Our approach integrates a gradient map and fractional-order total variation into the loss function to guide training. The gradient map provides structural guidance for edge preservation and directs the denoising branch to focus on sharp regions, thereby preventing over-smoothing. The fractional-order total variation mitigates detail ambiguity and excessive smoothing, ensuring rich textures and detailed information are retained. Extensive experiments yield an average Peak Signal-to-Noise Ratio (PSNR) of 31.52 dB and a Structural Similarity Index (SSIM) of 0.863 across various benchmark datasets, including McMaster, Kodak24, BSD68, Set12, and Urban100. DGGNet outperforms existing methods, such as RIDNet, which achieved a PSNR of 31.42 dB and an SSIM of 0.853, thereby establishing new benchmarks in speckle noise reduction. Full article
Show Figures

Figure 1

Figure 1
<p>System architecture of a speckle noise reduction system.</p>
Full article ">Figure 2
<p>The network structure of the proposed DGGNet. The DGGNet consists of one encoder and two decoders (one decoder works for the denoising branch, and the other works for the gradient branch). The gradient branch guides the denoising branch by fusing gradient information to enhance structure preservation.</p>
Full article ">Figure 3
<p>The flow diagram of the proposed DGGNet.</p>
Full article ">Figure 4
<p>Denoising visualization of our proposed DGGNet comparing competing methods on the ultrasound dataset. From left to right, we show the clean, noisy, and denoising results of SRAD [<a href="#B23-fractalfract-08-00666" class="html-bibr">23</a>], OBNLM [<a href="#B8-fractalfract-08-00666" class="html-bibr">8</a>], NLLRF [<a href="#B7-fractalfract-08-00666" class="html-bibr">7</a>], MHM [<a href="#B35-fractalfract-08-00666" class="html-bibr">35</a>], DnCNN [<a href="#B16-fractalfract-08-00666" class="html-bibr">16</a>], RIDNet [<a href="#B17-fractalfract-08-00666" class="html-bibr">17</a>], MSANN [<a href="#B20-fractalfract-08-00666" class="html-bibr">20</a>] and our proposed DGGNet.</p>
Full article ">Figure 5
<p>Denoising visualization of our proposed DGGNet comparing competing methods on the ultrasound dataset. From left to right, we show the ground truth, noisy, and denoising results of SRAD [<a href="#B23-fractalfract-08-00666" class="html-bibr">23</a>], OBNLM [<a href="#B8-fractalfract-08-00666" class="html-bibr">8</a>], NLLRF [<a href="#B7-fractalfract-08-00666" class="html-bibr">7</a>], DnCNN [<a href="#B16-fractalfract-08-00666" class="html-bibr">16</a>], MHM [<a href="#B35-fractalfract-08-00666" class="html-bibr">35</a>], RIDNet [<a href="#B17-fractalfract-08-00666" class="html-bibr">17</a>], MSANN [<a href="#B20-fractalfract-08-00666" class="html-bibr">20</a>], and our DGGNet.</p>
Full article ">Figure 6
<p>Denoising visualization of our proposed DGGNet compares competing methods on the realistic experiments data. From left to right, we show the noisy, denoising results of SRAD [<a href="#B23-fractalfract-08-00666" class="html-bibr">23</a>], OBNLM [<a href="#B8-fractalfract-08-00666" class="html-bibr">8</a>], NLLRF [<a href="#B7-fractalfract-08-00666" class="html-bibr">7</a>], MHM [<a href="#B35-fractalfract-08-00666" class="html-bibr">35</a>], DnCNN [<a href="#B16-fractalfract-08-00666" class="html-bibr">16</a>], RIDNet [<a href="#B17-fractalfract-08-00666" class="html-bibr">17</a>], MSANN [<a href="#B20-fractalfract-08-00666" class="html-bibr">20</a>] and our proposed DGGNet.</p>
Full article ">Figure 7
<p>Average feature maps of results of the upsampling block in the decoding architecture of the denoising branch in our proposed DGGNet. The top image in (<b>a</b>) is our denoising result, and the bottom image is the corresponding noisy image. (<b>b</b>–<b>e</b>) are the average feature maps of <math display="inline"><semantics> <mrow> <mn>16</mn> <mo>×</mo> <mn>16</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>32</mn> <mo>×</mo> <mn>32</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>64</mn> <mo>×</mo> <mn>64</mn> </mrow> </semantics></math>, and <math display="inline"><semantics> <mrow> <mn>128</mn> <mo>×</mo> <mn>128</mn> </mrow> </semantics></math> in the denoising branch of the decoding structure. The upper images of those image pairs are the average feature map of the denoising branch with the gradient branch, while the lower images are not. This shows that with the guide of the gradient branch in our DGGNet, the denoising result can preserve structure information better.</p>
Full article ">
18 pages, 3340 KiB  
Article
Impairment of Glucose Uptake Induced by Elevated Intracellular Ca2+ in Hippocampal Neurons of Malignant Hyperthermia-Susceptible Mice
by Arkady Uryash, Alfredo Mijares, Jose A. Adams and Jose R. Lopez
Cells 2024, 13(22), 1888; https://doi.org/10.3390/cells13221888 - 15 Nov 2024
Viewed by 244
Abstract
Malignant hyperthermia (MH) is a genetic disorder triggered by depolarizing muscle relaxants or halogenated inhalational anesthetics in genetically predisposed individuals who have a chronic elevated intracellular Ca2+ concentration ([Ca2+]i) in their muscle cells. We have reported that the [...] Read more.
Malignant hyperthermia (MH) is a genetic disorder triggered by depolarizing muscle relaxants or halogenated inhalational anesthetics in genetically predisposed individuals who have a chronic elevated intracellular Ca2+ concentration ([Ca2+]i) in their muscle cells. We have reported that the muscle dysregulation of [Ca2+]i impairs glucose uptake, leading to the development of insulin resistance in two rodent experimental models. In this study, we simultaneously measured the [Ca2+]i and glucose uptake in single enzymatically isolated hippocampal pyramidal neurons from wild-type (WT) and MH-R163C mice. The [Ca2+]i was recorded using a Ca2+-selective microelectrode, and the glucose uptake was assessed utilizing the fluorescent glucose analog 2-NBDG. The MH-R163C hippocampal neurons exhibited elevated [Ca2+]i and impaired insulin-dependent glucose uptake compared with the WT neurons. Additionally, exposure to isoflurane exacerbated these deficiencies in the MH-R163C neurons, while the WT neurons remained unaffected. Lowering [Ca2+]i using a Ca2+-free solution, SAR7334, or dantrolene increased the glucose uptake in the MH-R163C neurons without significantly affecting the WT neurons. However, further reduction of the [Ca2+]i below the physiological level using BAPTA decreased the insulin-dependent glucose uptake in both genotypes. Furthermore, the homogenates of the MH-R163C hippocampal neurons showed an altered protein expression of the PI3K/Akt signaling pathway and GLUT4 compared with the WT mice. Our study demonstrated that the chronic elevation of [Ca2+]i was sufficient to compromise the insulin-dependent glucose uptake in the MH-R163C hippocampal neurons. Moreover, reducing the [Ca2+]i within a specific range (100–130 nM) could reverse insulin resistance, a hallmark of type 2 diabetes mellitus (T2D). Full article
(This article belongs to the Section Cellular Pathology)
Show Figures

Figure 1

Figure 1
<p>Resting [Ca<sup>2+</sup>]<sub>i</sub> and insulin-dependent glucose uptake in the WT and MH-163C neurons. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 12–15, <span class="html-italic">n<sub>mice</sub></span> = 8. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 2
<p>Effects of the [Ca<sup>2+</sup>]<sub>e</sub>-free solution on the resting [Ca<sup>2+</sup>]<sub>I</sub> and insulin-dependent glucose uptake. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 12–15, <span class="html-italic">n<sub>mice</sub></span> = 9. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 3
<p>Effects of BAPTA on the resting [Ca<sup>2+</sup>]<sub>I</sub> and insulin-dependent glucose uptake. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 12–15, <span class="html-italic">n<sub>mice</sub></span> = 5. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 4
<p>Regulation of the [Ca<sup>2+</sup>]<sub>i</sub> and insulin-dependent glucose transport by SAR7334. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 12–15, <span class="html-italic">n<sub>mice</sub></span> = 8. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 5
<p>Modulation of the [Ca<sup>2+</sup>]<sub>i</sub> and insulin-dependent glucose uptake by dantrolene. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 11–15, <span class="html-italic">n<sub>mice</sub></span> = 7. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 6
<p>Isoflurane-induced changes in the [Ca<sup>2+</sup>]<sub>i</sub> and insulin-mediated glucose uptake in the MH-R163 neurons. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 12–15, <span class="html-italic">n<sub>mice</sub></span> = 8. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 7
<p>Dantrolene reduced the blood glucose levels in the MH-R163C mice. Values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 8–16, <span class="html-italic">n<sub>mice</sub></span> = 8. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 8
<p>Abnormal expressions of proteins of the insulin signaling pathway in the hippocampal neurons. Representative Western blot and densitometric analysis of PI3K, Akt, and AS160 protein expression in hippocampal homogenates. The grey circles represent individual experimental values recorded under each condition. The data were normalized to actin and expressed as the mean ± S.D. <span class="html-italic">n</span> = 4–6 per condition and <span class="html-italic">n<sub>mice</sub></span> = 5. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 9
<p>Phosphorylated/total protein ratio. The grey circles represent the individual experimental values recorded under each condition. The data were normalized to actin and expressed as the mean ± S.D. <span class="html-italic">n</span> = 4–6 per condition and <span class="html-italic">n<sub>mice</sub></span> = 5. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 10
<p>Decreased expression of GLUT4 in the hippocampus MH-R163C neurons. The data were normalized to actin, and the values are expressed as the mean ± SD. The grey circles represent individual experimental values recorded under each condition. <span class="html-italic">n =</span> 6, <span class="html-italic">n<sub>mice</sub></span> = 5. * denotes <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">
16 pages, 593 KiB  
Review
COVID-19 in Children and Vitamin D
by Teodoro Durá-Travé and Fidel Gallinas-Victoriano
Int. J. Mol. Sci. 2024, 25(22), 12205; https://doi.org/10.3390/ijms252212205 - 14 Nov 2024
Viewed by 373
Abstract
In December 2019, the so-called “coronavirus disease 2019” (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a “cytokine storm”. This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of [...] Read more.
In December 2019, the so-called “coronavirus disease 2019” (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a “cytokine storm”. This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm is analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain. Full article
Show Figures

Figure 1

Figure 1
<p>Severity of illness in children with COVID-19.</p>
Full article ">
14 pages, 2082 KiB  
Article
Dynamics of SARS-CoV-2 Spike RBD Protein Mutation and Pathogenicity Consequences in Indonesian Circulating Variants in 2020–2022
by Nabiel Muhammad Haykal, Fadilah Fadilah, Beti Ernawati Dewi, Linda Erlina, Aisyah Fitriannisa Prawiningrum and Badriul Hegar
Genes 2024, 15(11), 1468; https://doi.org/10.3390/genes15111468 - 14 Nov 2024
Viewed by 416
Abstract
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This [...] Read more.
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This research analyzes the mutation trend in various RBD samples from Indonesia published in the Global Initiative on Sharing All Influenza Data (GISAID) database using genomic profiling. Method: Patients in Indonesia infected with SARS-CoV-2, whose samples have been published in genomic databases, were selected for this research. The collected data were processed for analysis following several bioinformatics protocols: visualization into phylogenetic trees, 3D rendering, and the assessment of mutational impact. Results: In Indonesia, there are 25 unique SARS-CoV-2 clades and 318 unique SARS-CoV-2 RBD mutations from the earliest COVID-19 sample to samples collected in 2022, with T478K being the most prevalent RBD mutation and 22B being the most abundant clade. The Omicron variant has a lower docking score, higher protein destabilization, and higher KD than the Delta variant and the original virus. Conclusions: The study findings reveal a decreasing trend in virus pathogenicity as a potential trade-off to increase transmissibility via mutations in RBD over the years. Full article
(This article belongs to the Special Issue Bioinformatics of Human Diseases)
Show Figures

Figure 1

Figure 1
<p>SARS-CoV-2 NextStrain clades observed in Indonesia. This figure shows Indonesia’s 25 unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clades’ growth and fluctuations from 2020 to 2022. In 2020, the 19A clade (the original Wuhan strain) was most frequent from May to July, then gradually declined and was replaced by the 20A clade, which became dominant until the end of the year. In 2021, 20A was initially dominant but was overtaken by the 21J clade (a Delta variant subclade) in the year’s second half. By December 2021, the 21K clade (Omicron or BA.1) surged in prevalence. In 2022, 21K peaked in January but declined by June, replaced by the 22B clade (Omicron or BA.5). Later in 2022, 22F (Omicron or XBB) and 22E (Omicron or BQ.1) became the most observed clades. Overall, 22B was the most frequently observed clade, followed by 21K, 21J, 22F, and 21L.</p>
Full article ">Figure 2
<p>RBD mutations in Indonesia and their growth trends. This figure shows how receptor-binding domain (RBD) mutations in Indonesia evolved from 2020 to 2022. In March 2020, we started with just one unique mutation, A352S. Over time, the number of unique mutations grew significantly, reaching 318 by December 2022. From January to May 2021, N439K stayed dominant but was gradually overtaken by L452R, which peaked in July before declining. Between November and December 2021, 18 different RBD mutations rose significantly, including T478K and L452R. By 2022, the mutation landscape had become quite diverse, with 15 prominent RBD mutations occurring over 19,000 times, including T478K, S373P, S375F, S477N, N501Y, Q498R, Y505H, E484A, K417N, G339D, N440K, D405N, T376A, S371F, and R408S. Meanwhile, Q493R, G446S, G496S, S371L, and R346K started to decrease during this year.</p>
Full article ">Figure 3
<p>Graph showing COVID-19 cases and deaths, with the most frequent clades circulating in Indonesia. This graph shows the trends in coronavirus disease 2019 (COVID-19) cases and deaths in Indonesia, highlighting the month’s most common viral clades. As of 31 May 2023, Indonesia had reported 6,807,513 confirmed cases and 161,771 deaths. The highest peaks in new cases were in July 2021 (1,231,386 cases) and February 2022 (1,211,078 cases). The most deaths occurred in July 2021 (38,904 deaths) and August 2021 (35,628 deaths), predominantly of the 21J clade.</p>
Full article ">Figure 4
<p>Three-dimensional modeling of SARS-CoV-2 RBD mutations. (<b>a</b>) Delta variant RBD: this 3D model shows the Delta variant’s receptor-binding domain (RBD) mutations. The L452R mutation changes the structure from two coils to two sheets in certain regions, while the T478K mutation alters the coiled structure into a turn type, affecting nearby areas. These changes disrupt important bonds, impacting the overall structure. (<b>b</b>) Omicron variant RBD: this model illustrates the Omicron variant’s RBD mutations. Although the overall structure is similar to the original strain, the helix has a slight shift. Mutations at various positions lead to significant structural changes, including shifts from polar to nonpolar residues and additions of amine groups. These mutations impact the binding process of the SARS-CoV-2 RBD to ACE2 receptors and interact with antibodies.</p>
Full article ">
20 pages, 2550 KiB  
Article
Benzocarbazoledinones as SARS-CoV-2 Replication Inhibitors: Synthesis, Cell-Based Studies, Enzyme Inhibition, Molecular Modeling, and Pharmacokinetics Insights
by Luana G. de Souza, Eduarda A. Penna, Alice S. Rosa, Juliana C. da Silva, Edgar Schaeffer, Juliana V. Guimarães, Dennis M. de Paiva, Vinicius C. de Souza, Vivian Neuza S. Ferreira, Daniel D. C. Souza, Sylvia Roxo, Giovanna B. Conceição, Larissa E. C. Constant, Giovanna B. Frenzel, Matheus J. N. Landim, Maria Luiza P. Baltazar, Celimar Cinézia Silva, Ana Laura Macedo Brand, Julia Santos Nunes, Tadeu L. Montagnoli, Gisele Zapata-Sudo, Marina Amaral Alves, Diego Allonso, Priscila V. Z. Capriles Goliatt, Milene D. Miranda and Alcides J. M. da Silvaadd Show full author list remove Hide full author list
Viruses 2024, 16(11), 1768; https://doi.org/10.3390/v16111768 - 13 Nov 2024
Viewed by 532
Abstract
Endemic and pandemic viruses represent significant public health challenges, leading to substantial morbidity and mortality over time. The COVID-19 pandemic has underscored the urgent need for the development and discovery of new, potent antiviral agents. In this study, we present the synthesis and [...] Read more.
Endemic and pandemic viruses represent significant public health challenges, leading to substantial morbidity and mortality over time. The COVID-19 pandemic has underscored the urgent need for the development and discovery of new, potent antiviral agents. In this study, we present the synthesis and anti-SARS-CoV-2 activity of a series of benzocarbazoledinones, assessed using cell-based screening assays. Our results indicate that four compounds (4a, 4b, 4d, and 4i) exhibit EC50 values below 4 μM without cytotoxic effects in Calu-3 cells. Mechanistic investigations focused on the inhibition of the SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) have used enzymatic assays. Notably, compounds 4a and 4b showed Mpro inhibition activity with IC50 values of 0.11 ± 0.05 and 0.37 ± 0.05 µM, respectively. Furthermore, in silico molecular docking, physicochemical, and pharmacokinetic studies were conducted to validate the mechanism and assess bioavailability. Compound 4a was selected for preliminary drug-likeness analysis and in vivo pharmacokinetics investigations, which yielded promising results and corroborated the in vitro and in silico findings, reinforcing its potential as an anti-SARS-CoV-2 lead compound. Full article
Show Figures

Figure 1

Figure 1
<p>O-Methylmukanal (<b>1</b>), carprofen (<b>2</b>), emodine (<b>3</b>), benzocarbazoledinone (<b>4</b>).</p>
Full article ">Figure 2
<p>The rational approach to the design of benzocarbazoledinones (<b>4a</b>–<b>i</b>).</p>
Full article ">Figure 3
<p>The toxicity of the benzocarbazoledinone compounds. Calu-3 cells were treated with the compounds <b>4a</b>–<b>i</b> at 10 (<b>a</b>) or 100 (<b>b</b>) µM for 72 h for the methylene blue assay. The <span class="html-italic">p</span> values correspond *** <span class="html-italic">p</span> &lt; 0.001 (<span class="html-italic">n</span> = 6).</p>
Full article ">Figure 4
<p>Anti-SARS-CoV-2 activity of the benzocarbazoledinone compounds. Calu-3 cells infected with SARS-CoV-2 MOI 0.01 were treated with the compounds <b>4a</b>–<b>4i</b> at 10 µM for 24 h at 37 °C, 5% CO<sub>2</sub>. The <span class="html-italic">p</span> values correspond. *** <span class="html-italic">p</span> &lt; 0.001 (<span class="html-italic">n</span> = 6).</p>
Full article ">Figure 5
<p>The dose-dependent curves of compounds with the most anti-SARS-CoV-2 activity. Calu-3 cells infected with SARS-CoV-2 MOI 0.01 were treated with the compounds <b>4a</b>, <b>4b</b>, <b>4d</b>, and <b>4i</b> at various concentrations (0.6 to 10 µM) for 24 h at 37 °C, 5% CO<sub>2</sub> (<span class="html-italic">n</span> = 6).</p>
Full article ">Figure 6
<p>Best conformations of <b>4a</b> (<b>A</b>,<b>B</b>) and <b>4b</b> (<b>C</b>,<b>D</b>) compounds. These results were obtained from docking with the chain A of the 17,362 Mpro protein. The representations were made in three-dimensional and bi-dimensional models to show the interactions between the amino acid residues and the compounds as well as the pharmacophoric profile. The Mpro structure is represented in cartoon (grey). Compounds are represented in sticks: <b>4a</b> ((<b>A</b>), orange) and <b>4b</b> ((<b>C</b>), blue). The figures (<b>B</b>,<b>D</b>) show the specific chemical interactions, which are represented by colors: hydrophobic (green), polar (light blue), charged negative (orange), hydration site (white), and hydrogen bond (purple arrow). The images were generated using PyMOL version 2.1.0 and Maestro version 13.6.122, Schrödinger—LLC.</p>
Full article ">Figure 7
<p>These results were obtained from docking with chain A of the 6209 Mpro protein. The representations were created in both three-dimensional and two-dimensional models to illustrate the interactions between the amino acid residues and the compounds, as well as their pharmacophoric profiles. The Mpro structure is depicted in cartoon form: light orange (Nirmatrelvir) and purple (Atazanavir). The compounds are represented as sticks: Nirmatrelvir (dark red) and Atazanavir (dark green). Figures (<b>A</b>,<b>B</b>) represent Nirmatrelvir, while figures (<b>C</b>,<b>D</b>) represent Atazanavir, both illustrating their specific chemical interactions. In figures (<b>B</b>,<b>D</b>), the purple arrows highlight hydrogen bonds. The images were generated using PyMOL version 2.1.0 and Maestro version 13.6.122, Schrödinger—LLC.</p>
Full article ">Figure 8
<p>Plasma pharmacokinetics of <b>4a</b> after 5 mg/kg i.p. administration in rats (<span class="html-italic">n</span> = 4).</p>
Full article ">Scheme 1
<p>Synthesis of the benzocarbazoledinone derivatives (<b>4a</b>–<b>i</b>).</p>
Full article ">
19 pages, 19888 KiB  
Article
Improvement of Coal Mining-Induced Subsidence-Affected (MISA) Zone Irregular Boundary Delineation by MT-InSAR Techniques, UAV Photogrammetry, and Field Investigation
by Linan Liu, Nengxiong Xu, Wendy Zhou, Yan Qin and Shilong Luan
Remote Sens. 2024, 16(22), 4221; https://doi.org/10.3390/rs16224221 - 12 Nov 2024
Viewed by 559
Abstract
Coal mining-induced ground subsidence is a severe hazard that can damage property, infrastructure, and the environment in the vicinity when the deformation is not negligible. The boundary of a mining-induced subsidence-affected zone refers to the area beyond which the ground subsidence is less [...] Read more.
Coal mining-induced ground subsidence is a severe hazard that can damage property, infrastructure, and the environment in the vicinity when the deformation is not negligible. The boundary of a mining-induced subsidence-affected zone refers to the area beyond which the ground subsidence is less concerned. Accurately measuring mining-induced ground deformation is essential for delineating the irregular boundary of the impacted area. This study employs multitemporal interferometric synthetic aperture radar (MT-InSAR) techniques, including differential InSAR (DInSAR), InSAR stacking, and interferometric point target analysis (IPTA), to analyze coal mine subsidence and delineate the boundaries of the mining-impacted zones. DInSAR accurately reconstructs, locates, and detects the trend in mining-induced subsidence and correlates well with documented mining operations. The InSAR stacking method maps the spatial variation of the ground’s average line-of-sight (LOS) velocity over the mining area, delineating the boundary of the impacted zone. IPTA analysis combining multilook and single-pixel phases achieves millimeter-level surface measurement above tunnel alignments and measures unevenly distributed deformation fields. This study considers an average of 4 cm per year of surface deformation in the LOS direction as the subsidence threshold value for delineating the boundary of the mining-induced subsidence-affected (MISA) zone during the active coal mining stage. Interestingly, there are twin transportation tunnels near the mining area. The twin tunnels completed before the coal mining activities started were functioning well, but damage was observed after the mining began. Our study reveals the tunnels are located within the InSAR-derived MISA zone, although the tunnels approach the MISA boundary. As direct signs of subsidence, ground fissures have been identified near the tunnels via field investigations and UAV photogrammetry. Furthermore, the derived distribution of ground fissures validates and verifies InSAR measurements. The integrated approach of MT-InSAR, UVA photogrammetry, and field investigation developed in this study can be applied to delineate the irregular boundary of the MISA zone and study the accumulating effects of mining-induced subsidence on the performance of infrastructure in areas proximate to coal mining activities. Full article
Show Figures

Figure 1

Figure 1
<p>Distribution of coalfields in Shanxi, China, and the location of the study area.</p>
Full article ">Figure 2
<p>Investigated mining-induced ground movements and underground tunnel damage co-occurring with coal mining. (<b>a</b>) A map indicating the location of the longwall panel within the study area, ground surface settings, and faults; (<b>b</b>,<b>c</b>) mining-induced landslides and ground fissures; (<b>d</b>) fissure survey stations installed on the outcrop of the fault, (<b>e</b>–<b>h</b>) severe damage to the tunnels.</p>
Full article ">Figure 3
<p>The procedure of SAR dataset processing.</p>
Full article ">Figure 4
<p>Mining history reconstruction using SAR interferometry, with fringes indicating mining-induced ground subsidence and two red lines indicating an existing twin tunnel.</p>
Full article ">Figure 5
<p>The mean LOS velocity field (from July 2020 to May 2021) derived using the InSAR stacking technique.</p>
Full article ">Figure 6
<p>Ground fissures distributed between the excavation panel and tunnel alignments identified using UAV photogrammetry and field investigation. The irregular MISA zone boundary is derived from InSAR stacking measurements.</p>
Full article ">Figure 7
<p>Generalized cross-section of study area and subsidence profiles (not to scale).</p>
Full article ">Figure 8
<p>Schematic illustration (not to scale) summarizing the ground displacements affected by faults.</p>
Full article ">Figure 9
<p>Time-series analysis around tunnel alignment and interpolated subsidence profile.</p>
Full article ">Figure 10
<p>Representative time-series analysis along tunnel alignment of sections (<b>I</b>–<b>IV</b>). Note: (1) black dots represent time-series analysis of monitoring points, solid black lines indicate the trend in ground subsidence calculated by the MA method, and the red line represents ground surface as a reference of no ground movements; (2) negative values indicate subsidence, while positive values represent ground uplift in the LOS direction.</p>
Full article ">
25 pages, 25514 KiB  
Article
Phenotypic Timeline Kinetics, Integrative Networks, and Performance of T- and B-Cell Subsets Associated with Distinct Clinical Outcome of Severe COVID-19 Patients
by Gabriela de Oliveira, Ismael Artur Costa-Rocha, Nani Oliveira-Carvalho, Tâmilla Mayane Alves Fidelis dos Santos, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Vitor Hugo Simões Miranda, Roberta Oliveira Prado, Agnes Antônia Sampaio Pereira, Clarice Carvalho Alves, Joaquim Pedro Brito-de-Sousa, Laise Rodrigues Reis, Christiane Costa-Pereira, Camila Pacheco Silveira Martins da Mata, Vanessa Egídio Silveira Almeida, Liliane Martins dos Santos, Gregório Guilherme Almeida, Lis Ribeiro do Valle Antonelli, Jordana Grazziela Coelho-dos-Reis, Andréa Teixeira-Carvalho and Olindo Assis Martins-Filhoadd Show full author list remove Hide full author list
Microorganisms 2024, 12(11), 2272; https://doi.org/10.3390/microorganisms12112272 - 9 Nov 2024
Viewed by 604
Abstract
The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct [...] Read more.
The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct time points (baseline/D0; D7; D14-28) was used for ex vivo flow cytometry immunophenotyping. The data demonstrated a decrease at D0 in the frequency of CD3+ T-cells and CD4+ T-cells and an increase in B-cells with mixed activation/exhaustion profiles. Higher changes in B-cell and CD4+ T-cells at D7 were associated with discharge/death outcomes, respectively. Regardless of the lower T/B-cell connectivity at D0, distinct profiles from D7/D14-28 revealed that, while discharge was associated with increasing connectivity for B-cells, CD4+ and CD8+ T-cells death was related to increased connectivity involving B-cells, but with lower connections mediated by CD4+ T-cells. The CD4+CD38+ and CD8+CD69+ subsets accurately classified COVID-19 vs. healthy controls throughout the kinetic analysis. Binary logistic regression identified CD4+CD107a+, CD4+T-bet+, CD8+CD69+, and CD8+T-bet+ at D0 and CD4+CD45RO+CD27+ at D7 as subsets associated with disease outcomes. Results showed that distinct phenotypic timeline kinetics and integrative networks of T/B-cells are associated with COVID-19 outcomes that may subsidize the establishment of applicable biomarkers for clinical/therapeutic monitoring. Full article
(This article belongs to the Special Issue Immune Modulation to SARS-CoV-2 Vaccination and Infection)
Show Figures

Figure 1

Figure 1
<p>Phenotypic profile of T- and B-cells in severe COVID-19 patients at baseline (D0). Ex vivo phenotypic features of T- and B-cells were assessed in peripheral blood samples collected from COVID-19 patients at D0 (<span class="html-fig-inline" id="microorganisms-12-02272-i001"><img alt="Microorganisms 12 02272 i001" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i001.png"/></span>, n = 87) and healthy controls (<span class="html-fig-inline" id="microorganisms-12-02272-i002"><img alt="Microorganisms 12 02272 i002" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i002.png"/></span>, HCs, n = 13). Immunophenotypic staining was carried out as described in Material and Methods. Data are shown as a scattering distribution of individual values over bar charts representing the median percentage (%) of gated cells. Comparative analysis between COVID-19 and HCs was performed by the Mann–Whitney test, and the <span class="html-italic">p</span> values for significant differences are provided in the figure. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>), increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>), or unaltered (<span class="html-fig-inline" id="microorganisms-12-02272-i005"><img alt="Microorganisms 12 02272 i005" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i005.png"/></span>) percentages of cell subsets in COVID-19 as compared to HCs.</p>
Full article ">Figure 2
<p>Phenotypic profile of CD4<sup>+</sup> and CD8<sup>+</sup> T-cell subsets in severe COVID-19 patients at baseline (D0). Ex vivo phenotypic features of CD4<sup>+</sup> and CD8<sup>+</sup> T-cell subsets were assessed in peripheral blood samples collected from COVID-19 patients at D0 (<span class="html-fig-inline" id="microorganisms-12-02272-i001"><img alt="Microorganisms 12 02272 i001" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i001.png"/></span>, n = 87) and healthy controls (<span class="html-fig-inline" id="microorganisms-12-02272-i002"><img alt="Microorganisms 12 02272 i002" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i002.png"/></span>, HCs, n = 13). Immunophenotypic staining was carried out as described in Material and Methods. Data are shown as a scattering distribution of individual values over bar charts representing the median percentage (%) of gated cells. Comparative analysis between COVID-19 and HCs was performed by the Mann–Whitney test, and the <span class="html-italic">p</span> values for significant differences are provided in the figure. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>), increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>), or unaltered (<span class="html-fig-inline" id="microorganisms-12-02272-i005"><img alt="Microorganisms 12 02272 i005" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i005.png"/></span>) percentages of cell subsets in COVID-19 as compared to HCs.</p>
Full article ">Figure 3
<p>Phenotypic profile of T- and B-cells in severe COVID-19 patients at baseline (D0) according to disease outcome. Ex vivo phenotypic features of T- and B-cells were assessed in peripheral blood samples collected from COVID-19 patients at D0 (n = 71) and further categorized according to disease outcome into Discharge (<span class="html-fig-inline" id="microorganisms-12-02272-i006"><img alt="Microorganisms 12 02272 i006" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i006.png"/></span>, n = 38) or Death (<span class="html-fig-inline" id="microorganisms-12-02272-i007"><img alt="Microorganisms 12 02272 i007" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i007.png"/></span>, n = 33) groups and compared with the reference range (25th–75th interquartile) of healthy controls (HCs, n = 13, dashed lines). Immunophenotypic staining was carried out as described in Material and Methods. Data are shown as bar charts representing the median percentage (%, 95% CI) of gated cells. Comparative analyses amongst COVID-19 subgroups and HCs were performed using the Kruskal–Wallis test, followed by Dunn’s post-test for multiple comparisons. Significant differences are underscored by # for comparisons with HCs. Significant differences between COVID-19 subgroups were identified by connecting lines, and the <span class="html-italic">p</span> values for significant differences are provided in the figure. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>), increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>), or unaltered (<span class="html-fig-inline" id="microorganisms-12-02272-i005"><img alt="Microorganisms 12 02272 i005" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i005.png"/></span>) percentages of cell subsets in the COVID-19 subgroups as compared to HCs. Color frames highlight decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i008"><img alt="Microorganisms 12 02272 i008" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i008.png"/></span>) or increased (<span class="html-fig-inline" id="microorganisms-12-02272-i009"><img alt="Microorganisms 12 02272 i009" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i009.png"/></span>) percentages of cell subsets in COVID-19 patients progressing to Death compared to those evolving to Discharge.</p>
Full article ">Figure 4
<p>Phenotypic profile of CD4<sup>+</sup> (<b>A</b>) and CD8<sup>+</sup> (<b>B</b>) T-cell subsets in severe COVID-19 patients at baseline (D0) according to disease outcome. Ex vivo phenotypic features of CD4<sup>+</sup> and CD8<sup>+</sup> T-cell subsets were assessed in peripheral blood samples collected from COVID-19 patients at D0 (n = 71) and further categorized according to disease outcome into Discharge (<span class="html-fig-inline" id="microorganisms-12-02272-i006"><img alt="Microorganisms 12 02272 i006" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i006.png"/></span>, n = 38) or Death (<span class="html-fig-inline" id="microorganisms-12-02272-i007"><img alt="Microorganisms 12 02272 i007" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i007.png"/></span>, n = 33) groups, then compared with the reference range (25th–75th interquartile) of healthy controls (HCs, n = 13, dashed lines). Immunophenotypic staining was carried out as described in Material and Methods. Data are shown as bar charts representing the median percentage (%, 95% CI) of gated cells. Comparative analyses amongst COVID-19 subgroups and HCs were performed using the Kruskal–Wallis test, followed by Dunn’s post-test for multiple comparisons. Significant differences are underscored by # for comparisons with HCs. Significant differences between COVID-19 subgroups were identified by connecting lines, and the <span class="html-italic">p</span> values for significant differences are provided in the figure. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>), increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>), or unaltered (<span class="html-fig-inline" id="microorganisms-12-02272-i005"><img alt="Microorganisms 12 02272 i005" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i005.png"/></span>) percentages of cell subsets in COVID-19 subgroups as compared to HCs. Color frames highlight decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i008"><img alt="Microorganisms 12 02272 i008" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i008.png"/></span>) or increased (<span class="html-fig-inline" id="microorganisms-12-02272-i009"><img alt="Microorganisms 12 02272 i009" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i009.png"/></span>) percentages of cell subsets in COVID-19 patients progressing to Death compared to those evolving to Discharge.</p>
Full article ">Figure 5
<p>Timeline kinetics signature and cell phenotype profile in severe COVID-19 patients. The timeline kinetic profile of ex vivo phenotypic features of T- and B-cell subsets was assessed in peripheral blood samples collected from COVID-19 patients at distinct time points, including at D0 (<span class="html-fig-inline" id="microorganisms-12-02272-i001"><img alt="Microorganisms 12 02272 i001" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i001.png"/></span>, D0, n = 87), seven days (<span class="html-fig-inline" id="microorganisms-12-02272-i010"><img alt="Microorganisms 12 02272 i010" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i010.png"/></span>, D7, n = 37) and 14–28 days (<span class="html-fig-inline" id="microorganisms-12-02272-i011"><img alt="Microorganisms 12 02272 i011" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i011.png"/></span>, D14–28, n = 30) after inclusion in the study and compared with healthy controls (<span class="html-fig-inline" id="microorganisms-12-02272-i002"><img alt="Microorganisms 12 02272 i002" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i002.png"/></span>, HCs, n = 13). (<b>A</b>) Data analyses were carried out by converting the continuous variables measurements (percentage of gated cells) into categorical data reported as the proportion (%) of subjects with results above the global median cut-off (median values of all datasets), as described in Material and Methods. Color backgrounds underscore the cell subsets with the proportion of subjects below (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>) or above (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>) 50% (dashed line). (<b>B</b>) Color maps were assembled to underscore the cell subsets with the proportion of subjects below or above 50% according to the color key provided in the figure. (<b>C</b>) The number (#) of cell subsets with a proportion above 50% was calculated and data are shown in line charts to illustrate the cell phenotype profile along the days after inclusion. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>) or increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>) numbers of cell subsets in COVID-19 as compared to the reference values observed in HCs (continuous line).</p>
Full article ">Figure 6
<p>Timeline kinetics signature in severe COVID-19 patients according to disease outcome. The timeline kinetic profile of ex vivo phenotypic features of T- and B-cell subsets was assessed in peripheral blood samples collected from COVID-19 patients further categorized according to disease outcome into Discharge or Death and compared with healthy controls (<span class="html-fig-inline" id="microorganisms-12-02272-i002"><img alt="Microorganisms 12 02272 i002" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i002.png"/></span>, HCs, n = 13). Biological samples were obtained at distinct time points, including at D0 (<span class="html-fig-inline" id="microorganisms-12-02272-i001"><img alt="Microorganisms 12 02272 i001" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i001.png"/></span>, Discharge D0, n = 38; Death D0, n = 33), seven days (<span class="html-fig-inline" id="microorganisms-12-02272-i010"><img alt="Microorganisms 12 02272 i010" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i010.png"/></span>, Discharge D7, n = 14; Death D7, n = 14), and 14–28 days (<span class="html-fig-inline" id="microorganisms-12-02272-i011"><img alt="Microorganisms 12 02272 i011" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i011.png"/></span>, Discharge D14–28, n = 11; Death D14–28, n = 11) after inclusion in the study. Data analyses were carried out by converting the continuous variables measurements (percentage of gated cells) into categorical data reported as the proportion (%) of subjects with results above the global median cut-off (median values of all datasets), as described in Material and Methods. Color backgrounds underscore the cell subsets with the proportion of subjects below (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>) or above (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>) 50% (dashed line).</p>
Full article ">Figure 7
<p>Color map of timeline kinetics signature and cell phenotype profile in severe COVID-19 patients according to disease outcome. The timeline kinetic profile of ex vivo phenotypic features of T- and B-cell subsets was assessed in peripheral blood samples collected from COVID-19 patients further categorized according to disease outcome into Discharge or Death and compared with healthy controls (HCs, n = 13). Biological samples were obtained at distinct time points, including at baseline (<span class="html-fig-inline" id="microorganisms-12-02272-i001"><img alt="Microorganisms 12 02272 i001" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i001.png"/></span>, Discharge D0, n = 38; Death D0, n = 33), seven days (<span class="html-fig-inline" id="microorganisms-12-02272-i010"><img alt="Microorganisms 12 02272 i010" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i010.png"/></span>, Discharge D7, n = 14; Death D7, n = 14), and 14–28 days (<span class="html-fig-inline" id="microorganisms-12-02272-i011"><img alt="Microorganisms 12 02272 i011" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i011.png"/></span>, Discharge D14–28, n = 11; Death D14–28, n = 11) after inclusion in the study. Data analyses were carried out by converting the continuous variables measurements (percentage of gated cells) into categorical data to estimate the proportion (%) of subjects with results above the global median cut-off (median values of all datasets), as described in Material and Methods. (<b>A</b>) Color maps were assembled to underscore the cell subsets with the proportion of subjects below or above 50% according to the color key provided in the figure. (<b>B</b>) The number (#) of cell subsets with a proportion above 50% was calculated, and data were shown in line charts to illustrate the cell phenotype profile along the days after inclusion. Color backgrounds underscore decreased (<span class="html-fig-inline" id="microorganisms-12-02272-i003"><img alt="Microorganisms 12 02272 i003" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i003.png"/></span>) or increased (<span class="html-fig-inline" id="microorganisms-12-02272-i004"><img alt="Microorganisms 12 02272 i004" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i004.png"/></span>) numbers of cell subsets in COVID-19 as compared to the reference values observed in HCs (continuous line).</p>
Full article ">Figure 8
<p>Integrative network of T- and B-cell subsets in severe COVID-19 patients at baseline (D0). Integrative networks were assembled for ex vivo phenotypic features of T- and B-cell subsets from COVID-19 patients at D0 (n = 87), further categorized according to disease outcome into Discharge (n = 38) or Death (n = 33) and compared with healthy controls (HCs, n = 13). Data analyses were carried out by Spearman rank tests, and only significant strong correlations (<span class="html-italic">p</span> &lt; 0.05 and “r” scores ≥ |0.67|) were used to construct the integrative networks. (<b>A</b>) Cluster layout networks were constructed comprising four groups of cell phenotypes, including CD3<sup>+</sup> T-cells (<span class="html-fig-inline" id="microorganisms-12-02272-i012"><img alt="Microorganisms 12 02272 i012" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i012.png"/></span>), CD19<sup>+</sup> B-cells (<span class="html-fig-inline" id="microorganisms-12-02272-i013"><img alt="Microorganisms 12 02272 i013" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i013.png"/></span>), CD4<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i014"><img alt="Microorganisms 12 02272 i014" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i014.png"/></span>) and CD8<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i015"><img alt="Microorganisms 12 02272 i015" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i015.png"/></span>) T-cell subsets. Node border thickness is proportional to the number of strong correlations. Connecting edges (black lines) were used to link pairs of cell phenotypes displaying significant correlations. The number of strong correlations observed for each network is provided in the figure and used for comparative analysis between the COVID-19, HCs, and COVID-19 subgroups. The circular background area is proportional to the number of strong correlations of each cluster within the respective network. (<b>B</b>) Color map constructs were assembled to illustrate the overall connectivity between cell phenotypes in the COVID-19, HCs, and COVID-19 subgroups. A color key was employed to underscore the cell phenotypes with strong correlations.</p>
Full article ">Figure 9
<p>Integrative network kinetics of T- and B-cell subsets in severe COVID-19 patients according to disease outcome. (<b>A</b>) Integrative networks were assembled for ex vivo phenotypic features of T- and B-cell subsets from COVID-19 patients at D0 (n = 87), further categorized according to disease outcome into Discharge (n = 38) or Death (n = 33). Biological samples were obtained at distinct time points, including at baseline (Discharge D0, n = 38; Death D0, n = 33), seven days (Discharge D7, n = 14; Death D7, n = 14), and 14–28 days (Discharge D14–28, n = 11; Death D14–28, n = 11) after inclusion in the study. Data analyses were carried out by Spearman rank tests, and only significant strong correlations (<span class="html-italic">p</span> &lt; 0.05 and “r” scores ≥ |0.67|) were used to construct the integrative networks. Cluster layout networks were constructed comprising four groups of cell phenotypes, including CD3<sup>+</sup> T-cells (<span class="html-fig-inline" id="microorganisms-12-02272-i012"><img alt="Microorganisms 12 02272 i012" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i012.png"/></span>), CD19<sup>+</sup> B-cells (<span class="html-fig-inline" id="microorganisms-12-02272-i013"><img alt="Microorganisms 12 02272 i013" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i013.png"/></span>), CD4<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i014"><img alt="Microorganisms 12 02272 i014" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i014.png"/></span>), and CD8<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i015"><img alt="Microorganisms 12 02272 i015" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i015.png"/></span>) T-cell subsets. Node border thickness is proportional to the number of strong correlations. Connecting edges (black lines) were used to link pairs of cell phenotypes displaying significant correlations. The number of strong correlations observed for each network is provided in the figure and used for comparative analysis between COVID-19 and COVID-19 subgroups according to disease outcome. The circular background area is proportional to the number of strong correlations of each cluster within the respective network. (<b>B</b>) Color map constructs were assembled to illustrate the overall connectivity between cell phenotypes in the COVID-19 and COVID-19 subgroups. A color key was employed to underscore the cell phenotypes with strong correlations.</p>
Full article ">Figure 10
<p>High-dimensional analysis of T-cell subsets in severe COVID-19 patients along the timeline kinetics. Data dimensionality reduction was performed using the UMAP algorithm for selected T-cell subsets. The cell frequency values were extracted from FlowJo software, and the graphical representation shows the timeline kinetics (D0, D7, D14–28) of 8000 events for T CD4<sup>+</sup> and 5000 events for T CD8<sup>+</sup> populations. The overall frequency of each cell subset [PD-1<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i019"><img alt="Microorganisms 12 02272 i019" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i019.png"/></span>), CD62L<sup>−</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i016"><img alt="Microorganisms 12 02272 i016" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i016.png"/></span>), CD27<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i017"><img alt="Microorganisms 12 02272 i017" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i017.png"/></span>), and CD45RO<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i018"><img alt="Microorganisms 12 02272 i018" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i018.png"/></span>)] is illustrated in the dotted clusters and the frequencies are represented in the UMAP x vs. UMAP y axes.</p>
Full article ">Figure 11
<p>High-dimensional analysis of T-cell memory response in severe COVID-19 patients along the timeline kinetics. Data dimensionality reduction was performed by the UMAP algorithm for selected T-cell memory subsets. The cell frequency values were extracted from FlowJo software, and the graphical representation shows the timeline kinetics (D0, D7, D14–28) of 8.000 events for T CD4<sup>+</sup> and 5.000 events for T CD8<sup>+</sup> memory populations. The overall frequency of each cell memory subset [Naive/CD45RO<sup>−</sup>CD27<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i020"><img alt="Microorganisms 12 02272 i020" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i020.png"/></span>), early Effector/CD45RO<sup>−</sup>CD27<sup>−</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i021"><img alt="Microorganisms 12 02272 i021" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i021.png"/></span>), Central Memory/CD45RO<sup>+</sup>CD27<sup>+</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i022"><img alt="Microorganisms 12 02272 i022" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i022.png"/></span>), Effector Memory/CD45RO<sup>+</sup>CD27<sup>−</sup> (<span class="html-fig-inline" id="microorganisms-12-02272-i023"><img alt="Microorganisms 12 02272 i023" src="/microorganisms/microorganisms-12-02272/article_deploy/html/images/microorganisms-12-02272-i023.png"/></span>)] and the combined clusters off all memory subsets are illustrated in the dotted clusters, while the numbers of frequencies are represented in the UMAP x vs. UMAP y axes.</p>
Full article ">
15 pages, 452 KiB  
Article
Prediction Models for Elevated Cardiac Biomarkers from Previous Risk Factors and During the COVID-19 Pandemic in Residents of Trujillo City, Peru
by Joao Caballero-Vidal, Jorge Luis Díaz-Ortega, Irma Luz Yupari-Azabache, Luz Angélica Castro-Caracholi and Juan M. Alva Sevilla
Diagnostics 2024, 14(22), 2503; https://doi.org/10.3390/diagnostics14222503 - 8 Nov 2024
Viewed by 526
Abstract
Cardiac troponin serum concentration is a marker of myocardial injury, but NT-pro BNP is a marker of myocardial insufficiency. The purpose of this study was to determine binary logistic regression models to verify the possible association of cardiovascular risk indicators, pre-pandemic history, the [...] Read more.
Cardiac troponin serum concentration is a marker of myocardial injury, but NT-pro BNP is a marker of myocardial insufficiency. The purpose of this study was to determine binary logistic regression models to verify the possible association of cardiovascular risk indicators, pre-pandemic history, the number of times participants were infected with SARS-CoV-2, and vaccination against these biomarkers. A total of 281 residents of Trujillo city (Peru) participated between September and December 2023. We found a high prevalence of abdominal obesity of 55.2%; glycemia > 100 m/dL in 53%; hypercholesterolemia in 49.8%; low HDL in 71.9%; and LDL > 100 mg/dL in 78.6%. A total of 97.5% were vaccinated against COVID-19, and 92.2% had three or more doses. Also, 2.5% had cTnI > 0.05 ng/mL, and 3.3% had NT-proBNP > 125 pg/mL. The number of COVID-19 infections versus cTnI > 0.05 ng/mL presented an OR = 3.513 (p = 0.003), while for NT-proBNP > 125 pg/mL, the number of comorbidities presented an OR = 2.185 (p = 0.025) and LDL an OR = 0.209 (p = 0.025). A regression model was obtained in which there is an association between a higher number of COVID-19 infections and elevated cTnI values and a model implying an association of the number of comorbidities and LDL with the NT-proBNP level in a direct and inverse manner, respectively. Both models contribute to the prevention of cardiac damage. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
Show Figures

Figure 1

Figure 1
<p>Flow diagram of subject inclusion and exclusion.</p>
Full article ">
15 pages, 7750 KiB  
Article
Longitudinal Analysis of Binding Antibody Levels Against 39 Human Adenovirus Types in Sera from 60 Regular Blood Donors from Greifswald, Germany, over 5 Years from 2018 to 2022
by Xiaoyan Wang, Konstanze Aurich, Wenli Zhang, Anja Ehrhardt, Andreas Greinacher and Wibke Bayer
Viruses 2024, 16(11), 1747; https://doi.org/10.3390/v16111747 - 7 Nov 2024
Viewed by 688
Abstract
Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in [...] Read more.
Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in 2021 compared to sera collected before the SARS-CoV-2 pandemic. In this follow-up study, we wanted to verify this observation in a cohort of regular blood donors for whom serial samples were available. Therefore, HAdV-specific binding antibody levels were analyzed in sera collected over a 5-year period from 2018 to 2022 in a cohort of 60 regular donors to the blood bank of the University Hospital in Greifswald, Germany. Using ELISA-based assays, we quantified the binding antibody responses against 39 HAdV types. On the cohort level, we found largely stable antibody levels over the analyzed time period, with the highest antibody responses against HAdV-C1, -D25, -D26, -E4, -D10, -D27, -C5, -D75, -C2, and -C6. Only minor but significant reductions in comparison to the first serum samples from 2018 were detected for antibody levels in 2021 and 2022 against the low-prevalent types HAdV-A31, -D8, -D20, -D37, -D65, and -D69. On the other hand, we detected fluctuations in antibody levels on the individual level, with strong increases in antibody levels indicative of novel antigen contact. Interestingly, we frequently found simultaneous changes in antibody responses against multiple HAdV types, resulting in strong correlations of antibody responses against distinct clusters of HAdVs suggesting extensive cross-reactivity of HAdV-specific antibodies. To our knowledge, this is the first study of antibodies against a broad range of HAdV types in serum samples collected from a cohort of individuals over a prolonged period, and our data provide important insight into the long-term stability of HAdV-specific antibody levels. In this cohort of regular blood donors, we did not observe any major impact of the SARS-CoV-2 pandemic on HAdV immunity. Correlations of changes in antibody levels against different types indicate cross-reactivity of HAdV-specific antibodies that are important to consider for HAdV vector development. Our data also reveal possible candidates for future development of HAdV-based vectors. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
Show Figures

Figure 1

Figure 1
<p>Binding antibody levels against 39 HAdV types in sera from 60 blood donors from 2018 to 2022. Sera of blood donors were analyzed for binding antibody levels against 39 HAdV types from species A to G, as indicated. Dots represent the values obtained for the first sera obtained in 2018, whereas the violin plots outline the distribution of the binding antibody values of all subsequent serum samples. Each dot indicates an individual serum sample. The black lines indicate the mean values of the first serum samples; the dashed line indicates the mean value of binding antibody levels against HAdV-C5. Statistically significant differences of the antibody levels in the first serum samples against the individual HAdV types compared to HAdV-C5 are indicated by * (<span class="html-italic">p</span> &lt; 0.05; one-way analysis of variance on ranks with Dunn’s multiple comparison test).</p>
Full article ">Figure 2
<p>Bubble plot visualization of binding antibody levels over the observation period from 2018 to 2022. Binding antibody levels against the indicated HAdV types as shown in <a href="#viruses-16-01747-f001" class="html-fig">Figure 1</a>. The binding antibody levels in reference to the IgG standard are indicated by the size of the bubbles; the color indicates the relative change in percentage compared to the respective level in the donor’s first sample obtained in early 2018. The bubble plots show donors ordered by their arbitrary donor number arranged from left to right and the collection dates from 2018 to 2022 arranged from top to bottom. Ticks on the x axis indicate the positions 10, 20, 30, 40, and 50. bAb: binding antibody. * Indicates statistically significant differences of the antibody levels in the serum samples from the indicated year compared to antibody levels in the first serum samples from 2018 (<span class="html-italic">p</span> &lt; 0.05, one-way analysis of variance on ranks with Dunn’s multiple comparison test); no statistically significant differences were found for the comparison of the first set of samples from 2020 with samples from subsequent time points (<span class="html-italic">p</span> &gt; 0.05).</p>
Full article ">Figure 3
<p>Correlation analysis of binding antibody levels. (<b>A</b>) A Pearson correlation analysis was performed for the binding antibody levels against the different HAdV types, as shown in <a href="#viruses-16-01747-f002" class="html-fig">Figure 2</a> for each individual donor. Shown are the correlation maps for the indicated selected donors (for all donors, please refer to <a href="#app1-viruses-16-01747" class="html-app">Supplementary Figure S2</a>) with the binding antibody levels against the indicated HAdV types shown as bubble plots as in <a href="#viruses-16-01747-f002" class="html-fig">Figure 2</a> (binding antibody levels in reference to the IgG standard are indicated by the size of the bubbles; color indicates the relative change in percentage compared to the respective level in the donor’s first sample obtained in early 2018), on top of the correlation map, and the area under the curve of the binding antibody levels over the 5-year period shown on the left side of the correlation map. (<b>B</b>) A mean correlation matrix for the cohort was calculated from the individual correlation matrices per donor. Shown is a clustered correlation heatmap created using the average agglomeration clustering method.</p>
Full article ">
13 pages, 1838 KiB  
Article
Polymorphisms in the ACE I/D (rs4646994) and ACE2 G8790A (rs2285666) in Young Children Living in the Amazon Region and SARS-CoV-2 Infection
by Yan Cardoso Pimenta, Flávia Freitas de Oliveira Bonfim, Carlos Eduardo da Silva Figueiredo, Bruno Loreto de Aragão Pedroso, Mauro França Silva, Alberto Ignacio Olivares Olivares, Isabella Fernandes Delgado, José Paulo Gagliardi Leite and Marcia Terezinha Baroni de Moraes
Trop. Med. Infect. Dis. 2024, 9(11), 270; https://doi.org/10.3390/tropicalmed9110270 - 7 Nov 2024
Viewed by 438
Abstract
COVID-19 infection caused by SARS-CoV-2 continues to cause significant mortality and morbidity. ACE2 is a key regulator of the renin–angiotensin–aldosterone system (RAAS). Differences in COVID-19 severity are thought to be due to the imbalance of RAAS/ACE mutations. This retrospective study evaluated the detection [...] Read more.
COVID-19 infection caused by SARS-CoV-2 continues to cause significant mortality and morbidity. ACE2 is a key regulator of the renin–angiotensin–aldosterone system (RAAS). Differences in COVID-19 severity are thought to be due to the imbalance of RAAS/ACE mutations. This retrospective study evaluated the detection and genetic susceptibility to SARS-CoV-2 infection in 202 children ≤3 years of age living in the Amazon region in 2021. The angiotensin-converting enzyme ACE I/D (rs4646994) and ACE2 G8790A (rs2285666) polymorphisms were detected by SYBR GREEN real-time PCR and PCR-RFLP/Alul digestion, respectively. SARS-CoV-2 detection was performed by RT-qPCR in feces and saliva samples collected simultaneously from the same children presenting acute gastroenteritis (AGE) or acute respiratory infection (ARI). The frequency of SARS-CoV-2 detected by qRT-PCR in children was low (5.9%, 12/202), although higher in the group of children with AGE (8.9%, 9/101) than with ARI (2.9%, 3/101). Susceptibility to SARS-CoV-2 infection was not verified due to the low frequency. Homozygous II (rs4646994) children were the majority (87.1%, 176/202). Boys with genotype A (rs2285666) were more susceptible to ARI and pneumonia symptoms than AGE (OR = 3.8, 95% CI 1.4–10.3, p 0.007). Boys with genotype G (rs4646994) or the combination II + G were more susceptible to acquiring AGE. Surveillance, along with understanding their causes, is crucial to controlling ARI and COVID-19 in children living in low-income countries. Full article
(This article belongs to the Section Infectious Diseases)
Show Figures

Figure 1

Figure 1
<p>(<b>A</b>–<b>C</b>) The figure shows the electropherograms obtained from total DNA extracted from saliva samples of children with different ACE <span class="html-italic">rs4646994</span> polymorphisms: (<b>A</b>) overlapping of three peaks to II, ID, and DD genotypes, according to the melting temperature of 69 °C for II and 74 °C for DD; (<b>B</b>) II homozygous; (<b>C</b>) ID heterozygous; and (<b>D</b>) DD homozygous.</p>
Full article ">Figure 2
<p>(<b>A</b>,<b>B</b>) Maps of Roraima (RR) state (the countries of Venezuela and Guiana are indicated outside of these maps), where ACE <span class="html-italic">rs</span>4646994 (<b>A</b>) and ACE2 <span class="html-italic">rs</span>22856661 (<b>B</b>) polymorphisms are indicated in small colored circles. Numbers on the Roraima map indicate each of the 15 municipalities. The names collected and corresponding numbers are 1. Amajari, 2. Pacaraima, 3. Uiramutã, 4. Normandia, 5. Alto Alegre, 6. Boa Vista, 7. Bonfim, 8. Mucajaí, 9. Iracema, 10, Cantá, 11. Caracaraí, 12. Rorainópolis, 13. São Luiz do Anauá, 14. São José da Baliza, 15. Caroebe. <sup>1</sup> Boys with genotype A were grouped with homozygous AA girls, and boys with genotype G are grouped with homozygous GG girls since the ACE2 rs22856661 polymorphism is located on the X chromosome (Xp22) in intron 3.</p>
Full article ">
14 pages, 2691 KiB  
Article
An Evaluation of Organic Biostimulants as a Tool for the Sustainable Management of Viral Infections in Zucchini Plants
by Carla Libia Corrado, Livia Donati, Anna Taglienti, Luca Ferretti, Francesco Faggioli, Massimo Reverberi and Sabrina Bertin
Horticulturae 2024, 10(11), 1176; https://doi.org/10.3390/horticulturae10111176 - 7 Nov 2024
Viewed by 384
Abstract
In agriculture, new and sustainable strategies are increasingly demanded to integrate the traditional management of viral diseases based on the use of virus-free propagation materials and resistant or tolerant cultivars and on the control of insect vectors. Among the possible Integrated Pest Management [...] Read more.
In agriculture, new and sustainable strategies are increasingly demanded to integrate the traditional management of viral diseases based on the use of virus-free propagation materials and resistant or tolerant cultivars and on the control of insect vectors. Among the possible Integrated Pest Management (IPM) approaches, organic biostimulants have shown promising results in enhancing plant tolerance to virus infections by improving plant fitness and productivity and modulating metabolic functions. In this study, the combination of two organic biostimulants, Alert D-Max and Resil EVO Q, composed of seaweed and alfalfa extracts, enzymatic hydrolysates, and micronized zeolite, was applied on the leaves and roots of zucchini squashes, both healthy and infected by zucchini yellow mosaic virus (ZYMV). Four applications were scheduled based on ZYMV inoculation timing, and plant vegetative and reproductive parameters were recorded along with the virus titre and symptom severity. The modulation of the expression of specific genes potentially involved in pattern-triggered immunity (PTI), systemic acquired resistance (SAR), and oxidative stress defence pathways was also investigated. Besides increasing the general fitness of the healthy plants, the biostimulants significantly improved the production of flowers and fruits of the infected plants, with a potential positive impact on their productivity. The repeated biostimulant applications also led to a one-tenth reduction in ZYMV titre over time and induced a progressive slowdown of symptom severity. Genes associated with SAR and PTI were up-regulated after biostimulant applications, suggesting the biostimulant-based priming of plant defence mechanisms. Due to the observed beneficial effects, the tested biostimulant mix can be an effective component of the IPM of cucurbit crops, acting as a sustainable practice for enhancing plant fitness and tolerance to potyviruses. Full article
(This article belongs to the Section Biotic and Abiotic Stress)
Show Figures

Figure 1

Figure 1
<p>Analysis of vegetative parameters. (<b>a</b>) Number of leaves and (<b>b</b>) dry weight (grams) produced by healthy treated (HT), infected treated (IT), healthy untreated (HU), and infected untreated (IU) plants at 45 d.p.i. Results are expressed as mean values ± standard error (±SEM) recorded from 12 plants per treatment in three independent experimental trials. Different letters indicate statistically significant differences (Tukey test, <span class="html-italic">p</span> value &lt; 0.05).</p>
Full article ">Figure 2
<p>Plant growth and size. This figure shows 35-day old plants representative for the biomass produced within each of the four treatments: healthy treated (HT), infected treated (IT), healthy untreated (HU), and infected untreated (IU) plants.</p>
Full article ">Figure 3
<p>Analysis of reproductive parameters. Number of (<b>a</b>) flowers and (<b>b</b>) fruits produced by healthy treated (HT), infected treated (IT), healthy untreated (HU), and infected untreated (IU) plants at 45 d.p.i. Results are expressed as mean values ± standard error (±SEM) recorded from 12 plants per treatment in three independent experimental trials. Different letters indicate statistically significant differences (Tukey test, <span class="html-italic">p</span> value &lt; 0.05).</p>
Full article ">Figure 4
<p>Evaluation of ZYMV symptoms. Symptoms observed in ZYMV-infected treated (IT) and ZYMV-infected untreated (IU) plants at 22 and 36 d.p.i. No symptoms were observed in healthy plants (healthy treated, HT, and healthy untreated, HU) at 36 d.p.i.</p>
Full article ">Figure 5
<p>Analysis of ZYMV titre. Relative quantification of ZYMV at 8, 22, and 36 d.p.i. measured by using 2<sup>−ΔΔCt</sup> method and setting ZYMV-infected untreated samples (IU) as control and <span class="html-italic">EF-1α</span> as reference gene (<span class="html-italic">EF-1α</span> expression in IU = 1). Results are expressed as mean values ± standard error (±SEM) obtained from two technical replicates of three pooled biological replicates produced in three independent experimental repeats. (*) indicates significant fold changes, i.e., values above 2.0 (up-regulation) or below 0.5 (down-regulation) with confidence interval that did not comprise value of 1 (no regulation) at <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 6
<p>Gene expression analysis. Relative expression of (<b>a</b>) <span class="html-italic">peroxidase</span> (<span class="html-italic">POD</span>) and (<b>b</b>) <span class="html-italic">pathogenesis-related gene 1</span> (<span class="html-italic">PR1</span>) at 8, 22, and 36 d.p.i. measured by using 2<sup>−ΔΔCt</sup> method and setting ZYMV-infected untreated samples (IU) as control and <span class="html-italic">EF-1α</span> as reference gene (<span class="html-italic">EF-1α</span> expression in IU = 1). Results are expressed as mean values ± standard error (±SEM) obtained from two technical replicates of three pooled biological replicates produced in three independent experimental repeats. (*) indicates significant fold changes, i.e., values above 2.0 (up-regulation) or below 0.5 (down-regulation) with confidence interval that did not comprise value of 1 (no regulation) at <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">
24 pages, 10905 KiB  
Article
Benchmark Investigation of SARS-CoV-2 Mutants’ Immune Escape with 2B04 Murine Antibody: A Step Towards Unraveling a Larger Picture
by Karina Kapusta, Allyson McGowan, Santanu Banerjee, Jing Wang, Wojciech Kolodziejczyk and Jerzy Leszczynski
Curr. Issues Mol. Biol. 2024, 46(11), 12550-12573; https://doi.org/10.3390/cimb46110745 - 6 Nov 2024
Viewed by 397
Abstract
Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. [...] Read more.
Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. Nonetheless, reinfection by newly emerging subvariants, particularly the latest JN.1 strain, remains common. The rapid mutation of this virus demands a fast response from the scientific community in case of an emergency. While the immune escape of earlier variants was extensively investigated, one still needs a comprehensive understanding of how specific mutations, especially in the newest subvariants, influence the antigenic escape of the pathogen. Here, we tested comprehensive in silico approaches to identify methods for fast and accurate prediction of antibody neutralization by various mutants. As a benchmark, we modeled the complexes of the murine antibody 2B04, which neutralizes infection by preventing the SARS-CoV-2 spike glycoprotein’s association with angiotensin-converting enzyme (ACE2). Complexes with the wild-type, B.1.1.7 Alpha, and B.1.427/429 Epsilon SARS-CoV-2 variants were used as positive controls, while complexes with the B.1.351 Beta, P.1 Gamma, B.1.617.2 Delta, B.1.617.1 Kappa, BA.1 Omicron, and the newest JN.1 Omicron variants were used as decoys. Three essentially different algorithms were employed: forced placement based on a template, followed by two steps of extended molecular dynamics simulations; protein–protein docking utilizing PIPER (an FFT-based method extended for use with pairwise interaction potentials); and the AlphaFold 3.0 model for complex structure prediction. Homology modeling was used to assess the 3D structure of the newly emerged JN.1 Omicron subvariant, whose crystallographic structure is not yet available in the Protein Database. After a careful comparison of these three approaches, we were able to identify the pros and cons of each method. Protein–protein docking yielded two false-positive results, while manual placement reinforced by molecular dynamics produced one false positive and one false negative. In contrast, AlphaFold resulted in only one doubtful result and a higher overall accuracy-to-time ratio. The reasons for inaccuracies and potential pitfalls of various approaches are carefully explained. In addition to a comparative analysis of methods, some mechanisms of immune escape are elucidated herein. This provides a critical foundation for improving the predictive accuracy of vaccine efficacy against new viral subvariants, introducing accurate methodologies, and pinpointing potential challenges. Full article
Show Figures

Figure 1

Figure 1
<p>Mutations in SARS-CoV-2 receptor-binding domain: (<b>a</b>) mutation progression over time (Figures are adapted from Nextstrain.org, used under a CC-BY-4.0 license; <a href="https://nextstrain.org/ncov/gisaid/global/all-time" target="_blank">https://nextstrain.org/ncov/gisaid/global/all-time</a> (accessed on 1 May 2024)); (<b>b</b>) scheme of spike neutralization by 2B04 antibody; (<b>c</b>) list of mutations occurring in RBD of selected mutant structures.</p>
Full article ">Figure 2
<p>Schematic representation of approaches used in this study.</p>
Full article ">Figure 3
<p>MD simulation of the Omicron JN.1 RBD’s homology model: (<b>a</b>) scheme of a general homology modeling approach and superposition of the 10 most populated clusters (colored ribbons) after 200 ns MD simulation and reference Omicron BA.1 structured (black ribbons) with labeled mutated residues; (<b>b</b>) RMSD plots; (<b>c</b>) RMSF plots; (<b>d</b>) secondary protein structure.</p>
Full article ">Figure 4
<p>Results of the preliminary 100 ns molecular dynamics simulations: (<b>a</b>) RMSD plots; (<b>b</b>) RBD RMSF plot; (<b>c</b>) antibody RMSF plot (H and L stand for antibody subunits); (<b>d</b>) superposition of the most populated clusters from the molecular dynamics trajectory (Epsilon* is the fifth most populated cluster with the lowest RMSD). Average GPU time: 6H 28′ 54″; average total rate per step: 375.36 ns/day; Linux-x86_64. Resources: Z8G4 2.4 GHz Intel Xeon Silver 4214R 12-Core 64GB 2933 MHz DDR4 ECC Registered RAM NVIDIA Quadro RTX A5000 1TB.</p>
Full article ">Figure 5
<p>Results of the 200 ns molecular dynamics simulations: (<b>a</b>) RMSD plots; (<b>b</b>) RBD RMSF plot; (<b>c</b>) antibody RMSF plot (H and L stands for antibody subunits); (<b>d</b>) superposition of the most populated clusters from the molecular dynamics trajectory (Epsilon* is a 200 ns simulation with the initial structure derived from the fifth most populated cluster of the 100 ns preliminary MD simulation). Average GPU time: 45H 19′ 12″; average total rate per step: 106.40 ns/day; Linux-x86_64, Resources: Z8G4 2.4 GHz Intel Xeon Silver 4214R 12-Core 64GB 2933 MHz DDR4 ECC Registered RAM NVIDIA Quadro RTX A5000 1TB.</p>
Full article ">Figure 6
<p>Protein–protein interactions for the most populated clusters of a 200 ns MD simulation of the RBD (residues colored in blue) complexed with the 2B04 (residues colored in red) antibody: (<b>a</b>) WT; (<b>b</b>) Alpha; (<b>c</b>) Beta; (<b>d</b>) Gamma; (<b>e</b>) Delta; (<b>f</b>) Kappa; (<b>g</b>) Epsilon; (<b>h</b>) Epsilon* (with the initial structure derived from the fifth most populated cluster of the 100 ns preliminary MD simulation); (<b>i</b>) Omicron BA.1; (<b>j</b>) Omicron JN.1.</p>
Full article ">Figure 7
<p>Results of protein–protein docking: (<b>a</b>) pose numbers of the docked structures with the corresponding lowest RMSD value, PIPER pose energy and score, and RMSD for each complex; superposition of all 30 docked poses on the reference structure (colored in black) for (<b>b</b>) WT; (<b>c</b>) Alpha; (<b>d</b>) Beta; (<b>e</b>) Gamma; (<b>f</b>) Delta; (<b>g</b>) Kappa; (<b>h</b>) Epsilon; (<b>i</b>) Omicron BA.1; (<b>j</b>) Omicron JN.1 (the color of the pose with the lowest RMSD and its order are illustrated).</p>
Full article ">Figure 8
<p>Results of AlphaFold prediction: predicted aligned error (PAE) matrix (darker is more confident) for complexes of (<b>a</b>) WT; (<b>b</b>) Alpha; (<b>c</b>) Beta; (<b>d</b>) Gamma; (<b>e</b>) Delta; (<b>f</b>) Kappa; (<b>g</b>) Epsilon; (<b>h</b>) Omicron BA.1; (<b>i</b>) Omicron JN.1; (<b>j</b>) prediction scores and RMSDs compared to the reference structure; (<b>k</b>) superposition of complex predictions based on the reference structure (colored in blue).</p>
Full article ">Figure 9
<p>Correlation between predicted parameters with experimental data and general discussion: (<b>a</b>) results of a forced placement approach; (<b>b</b>) hydrophobic/hydrophilic surface of an antibody and the role of critical residues E484 and F486; (<b>c</b>) results of protein–protein docking; (<b>d</b>) results of AlphFold prediction.</p>
Full article ">Figure 10
<p>Protein–protein interactions predicted by different approaches: (<b>a</b>) Epsilon-2B04 complex as a result of a forced placement (model 1); (<b>b</b>) Epsilon-2B04 complex as a result of a forced placement (model 2); (<b>c</b>) Epsilon-2B04 complex as a result a protein–protein docking; (<b>d</b>) Epsilon-2B04 complex as a result of an AlphaFold prediction; (<b>e</b>) Kappa-2B04 complex as a result of a forced placement; (<b>f</b>) Kappa-2B04 complex as the result of protein–protein docking.</p>
Full article ">
18 pages, 4620 KiB  
Review
The Effect of Vitamin D Supplementation Post COVID-19 Infection and Related Outcomes: A Systematic Review and Meta-Analysis
by Marina Sartini, Filippo Del Puente, Alessio Carbone, Elisa Schinca, Gianluca Ottria, Chiara Dupont, Carolina Piccinini, Martino Oliva and Maria Luisa Cristina
Nutrients 2024, 16(22), 3794; https://doi.org/10.3390/nu16223794 - 5 Nov 2024
Viewed by 1060
Abstract
Background: Vitamin D’s role in COVID-19 management remains controversial. This meta-analysis aimed to evaluate the efficacy of vitamin D supplementation in patients with SARS-CoV-2 infection, focusing on mortality, intensive care unit (ICU) admissions, intubation rates, and hospital length of stay (LOS). Methods: A [...] Read more.
Background: Vitamin D’s role in COVID-19 management remains controversial. This meta-analysis aimed to evaluate the efficacy of vitamin D supplementation in patients with SARS-CoV-2 infection, focusing on mortality, intensive care unit (ICU) admissions, intubation rates, and hospital length of stay (LOS). Methods: A systematic review of PubMed/MEDLINE, Scopus, Cochrane, and Google Scholar databases was conducted. Randomized controlled trials (RCTs) and analytical studies investigating vitamin D supplementation in COVID-19 patients were included. The meta-analysis was performed using STATA MP 18.5, employing random-effect or fixed-effect models based on heterogeneity. Results: Twenty-nine studies (twenty-one RCTs, eight analytical) were analyzed. Vitamin D supplementation significantly reduced ICU admissions (OR = 0.55, 95% CI: 0.37 to 0.79) in RCTs and analytical studies (OR = 0.35, 95% CI: 0.18 to 0.66). Intubation rates were significantly reduced in RCTs (OR = 0.50, 95% CI: 0.27 to 0.92). Mortality reduction was significant in analytical studies (OR = 0.45, 95% CI: 0.24 to 0.86) but not in RCTs (OR = 0.80, 95% CI: 0.61 to 1.04). Subgroup analyses revealed more pronounced effects in older patients and severe COVID-19 cases. LOS showed a non-significant reduction (mean difference = −0.62 days, 95% CI: −1.41 to 0.18). Conclusions: This meta-analysis suggests potential benefits of vitamin D supplementation in COVID-19 patients, particularly in reducing ICU admissions. However, the evidence varies across outcomes and patient subgroups. Discrepancies between RCTs and analytical studies highlight the need for further large-scale, well-designed trials accounting for baseline vitamin D status, standardized supplementation protocols, and patient characteristics to inform clinical guidelines for vitamin D use in COVID-19 management. Full article
(This article belongs to the Section Micronutrients and Human Health)
Show Figures

Figure 1

Figure 1
<p>Traffic light plots of Risk of Bias for RCT (<b>a</b>) and for analytical studies (<b>b</b>). (<b>a</b>) D1: Was the study described as randomized, a randomized trial, a randomized clinical trial, or an RCT? D2: Was the method of randomization adequate (i.e., use of randomly generated assignment)? D3: Was the treatment allocation concealed (so that assignments could not be predicted)? D4: Were study participants and providers blinded to treatment group assignment? D5: Were the people assessing the outcomes blinded to the participants’ group assignments? D6: Were the groups similar at baseline in terms of important characteristics that could affect outcomes (e.g., demographics, risk factors, comorbid conditions)? D7: Was the overall drop-out rate from the study at the endpoint 20% or lower than the number allocated to treatment? D8: Was the differential drop-out rate (between treatment groups) at endpoint 15 percentage points or lower? D9: Was there a high adherence to the intervention protocols for each treatment group? D10: Were other interventions avoided or similar in the groups (e.g., similar background treatments)? D11: Were outcomes assessed using valid and reliable measures implemented consistently across all study participants? D12: Did the authors report that the sample size was sufficiently large to detect a difference in the main outcome between groups with at least 80% power? D13: Were outcomes reported or subgroups analyzed prespecified (i.e., identified before analyses were conducted)? D14: Were all randomized participants analyzed in the group to which they were originally assigned (i.e., did they use an intention-to-treat analysis)? (<b>b</b>) D1: Was the research question or objective in this paper clearly stated? D2: Was the study population clearly specified and defined? D3: Was the participation rate of eligible persons at least 50%? D4: Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? D5: Was a sample size justification, power description, or variance and effect estimates provided? D6: For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? D7: Was the timeframe sufficient, such that one could reasonably expect to see an association between exposure and outcome if it existed? D8: For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of low exposure or exposure measured as a continuous variable)? D9: Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? D10: Was the exposure(s) assessed more than once over time? D11: Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? D12: Were the outcome assessors blinded to the exposure status of participants? D13: Was the loss to follow-up after baseline 20% or less? D14: Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?</p>
Full article ">Figure 1 Cont.
<p>Traffic light plots of Risk of Bias for RCT (<b>a</b>) and for analytical studies (<b>b</b>). (<b>a</b>) D1: Was the study described as randomized, a randomized trial, a randomized clinical trial, or an RCT? D2: Was the method of randomization adequate (i.e., use of randomly generated assignment)? D3: Was the treatment allocation concealed (so that assignments could not be predicted)? D4: Were study participants and providers blinded to treatment group assignment? D5: Were the people assessing the outcomes blinded to the participants’ group assignments? D6: Were the groups similar at baseline in terms of important characteristics that could affect outcomes (e.g., demographics, risk factors, comorbid conditions)? D7: Was the overall drop-out rate from the study at the endpoint 20% or lower than the number allocated to treatment? D8: Was the differential drop-out rate (between treatment groups) at endpoint 15 percentage points or lower? D9: Was there a high adherence to the intervention protocols for each treatment group? D10: Were other interventions avoided or similar in the groups (e.g., similar background treatments)? D11: Were outcomes assessed using valid and reliable measures implemented consistently across all study participants? D12: Did the authors report that the sample size was sufficiently large to detect a difference in the main outcome between groups with at least 80% power? D13: Were outcomes reported or subgroups analyzed prespecified (i.e., identified before analyses were conducted)? D14: Were all randomized participants analyzed in the group to which they were originally assigned (i.e., did they use an intention-to-treat analysis)? (<b>b</b>) D1: Was the research question or objective in this paper clearly stated? D2: Was the study population clearly specified and defined? D3: Was the participation rate of eligible persons at least 50%? D4: Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants? D5: Was a sample size justification, power description, or variance and effect estimates provided? D6: For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured? D7: Was the timeframe sufficient, such that one could reasonably expect to see an association between exposure and outcome if it existed? D8: For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of low exposure or exposure measured as a continuous variable)? D9: Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? D10: Was the exposure(s) assessed more than once over time? D11: Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants? D12: Were the outcome assessors blinded to the exposure status of participants? D13: Was the loss to follow-up after baseline 20% or less? D14: Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?</p>
Full article ">Figure 2
<p>PRISMA 2020 flow diagram of study selection, inclusion, and synthesis.</p>
Full article ">Figure 3
<p>Forest plot of Impact of Vitamin D supplementation on ICU admission by age only for RCT studies. * We used a Fixed Effect Mantel-Haenszel model for age &gt; 65 years [<a href="#B40-nutrients-16-03794" class="html-bibr">40</a>,<a href="#B42-nutrients-16-03794" class="html-bibr">42</a>,<a href="#B43-nutrients-16-03794" class="html-bibr">43</a>,<a href="#B44-nutrients-16-03794" class="html-bibr">44</a>,<a href="#B46-nutrients-16-03794" class="html-bibr">46</a>,<a href="#B48-nutrients-16-03794" class="html-bibr">48</a>,<a href="#B49-nutrients-16-03794" class="html-bibr">49</a>,<a href="#B50-nutrients-16-03794" class="html-bibr">50</a>,<a href="#B53-nutrients-16-03794" class="html-bibr">53</a>,<a href="#B54-nutrients-16-03794" class="html-bibr">54</a>,<a href="#B55-nutrients-16-03794" class="html-bibr">55</a>,<a href="#B57-nutrients-16-03794" class="html-bibr">57</a>,<a href="#B65-nutrients-16-03794" class="html-bibr">65</a>,<a href="#B66-nutrients-16-03794" class="html-bibr">66</a>].</p>
Full article ">Figure 4
<p>Forest plot of Impact of Vitamin D supplementation on ICU admission for analytical studies [<a href="#B41-nutrients-16-03794" class="html-bibr">41</a>,<a href="#B45-nutrients-16-03794" class="html-bibr">45</a>,<a href="#B52-nutrients-16-03794" class="html-bibr">52</a>,<a href="#B59-nutrients-16-03794" class="html-bibr">59</a>,<a href="#B61-nutrients-16-03794" class="html-bibr">61</a>].</p>
Full article ">Figure 5
<p>Forest plot of Impact of Vitamin D supplementation on mortality for analytical studies [<a href="#B41-nutrients-16-03794" class="html-bibr">41</a>,<a href="#B45-nutrients-16-03794" class="html-bibr">45</a>,<a href="#B52-nutrients-16-03794" class="html-bibr">52</a>,<a href="#B60-nutrients-16-03794" class="html-bibr">60</a>,<a href="#B61-nutrients-16-03794" class="html-bibr">61</a>,<a href="#B62-nutrients-16-03794" class="html-bibr">62</a>,<a href="#B63-nutrients-16-03794" class="html-bibr">63</a>].</p>
Full article ">Figure 6
<p>Forest plot of Impact of Vitamin D supplementation on risk of intubation for RCT studies [<a href="#B42-nutrients-16-03794" class="html-bibr">42</a>,<a href="#B43-nutrients-16-03794" class="html-bibr">43</a>,<a href="#B44-nutrients-16-03794" class="html-bibr">44</a>,<a href="#B47-nutrients-16-03794" class="html-bibr">47</a>,<a href="#B50-nutrients-16-03794" class="html-bibr">50</a>,<a href="#B53-nutrients-16-03794" class="html-bibr">53</a>,<a href="#B54-nutrients-16-03794" class="html-bibr">54</a>,<a href="#B57-nutrients-16-03794" class="html-bibr">57</a>,<a href="#B64-nutrients-16-03794" class="html-bibr">64</a>].</p>
Full article ">Figure 7
<p>Forest plot of Impact of Vitamin D supplementation on Hospital Length of Stay [<a href="#B42-nutrients-16-03794" class="html-bibr">42</a>,<a href="#B43-nutrients-16-03794" class="html-bibr">43</a>,<a href="#B44-nutrients-16-03794" class="html-bibr">44</a>,<a href="#B46-nutrients-16-03794" class="html-bibr">46</a>,<a href="#B48-nutrients-16-03794" class="html-bibr">48</a>,<a href="#B49-nutrients-16-03794" class="html-bibr">49</a>,<a href="#B50-nutrients-16-03794" class="html-bibr">50</a>,<a href="#B51-nutrients-16-03794" class="html-bibr">51</a>,<a href="#B53-nutrients-16-03794" class="html-bibr">53</a>,<a href="#B54-nutrients-16-03794" class="html-bibr">54</a>,<a href="#B58-nutrients-16-03794" class="html-bibr">58</a>,<a href="#B65-nutrients-16-03794" class="html-bibr">65</a>,<a href="#B66-nutrients-16-03794" class="html-bibr">66</a>].</p>
Full article ">
Back to TopTop