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Tailored Molecular and Pathophysiological Approach to COVID-19: Ambition and Need

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 22973

Special Issue Editor

Humanitas Institute, Gradenigo Hospital, Torino, Italy
Interests: non-classical renin-angiotensin system; liver cirrhosis; COVID-19; renal failure; multiorgan failure

Special Issue Information

Dear Colleagues,

During this SARS-CoV-2 pandemic, significant areas of concern are, first, lack of specific therapies for severe cases of COVID-19 and, second, fear of emergence of viral variants that could make previous management strategies ineffective.

Common to all SARS-CoV-2 variants is the direct damage to the subtle mechanisms of the renin–angiotensin system that presides over a large part of systemic inflammation and hemodynamics, i.e., the damage to ACE2 (the cell membrane viral receptor) and ACE2-driven angiotensin 1–7 production. Attempts at replacing defective ACE2 or angiotensin 1–7 functions during the clinical course of COVID-19 have been common and pursued all over the world.

After two years of pandemic, a tailored and sensible approach to COVID-19 must include: a) a definition of the mechanisms of inflammatory disease that follow cellular infection; b) cognition of the most frequently found viral variants in terms of genomic and antigenic mutations; and c) identification of biomolecular viral and host targets, the latter being the non-classical renin-angiotensin system, that could be acted upon pharmacologically.

These aims warrant renewed international and multi-disciplinary efforts.

Dr. Sansoè Giovanni
Guest Editor

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Keywords

  • SARS-CoV-2
  • COVID-19
  • renin angiotensin system
  • angiotensins
  • ACE2
  • ACE
  • chymase
  • neprilysin
  • metallopeptidases

Published Papers (12 papers)

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Research

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21 pages, 1517 KiB  
Article
A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers–Danlos and Long COVID-19 Syndromes
by Golder N. Wilson
Curr. Issues Mol. Biol. 2023, 45(7), 6003-6023; https://doi.org/10.3390/cimb45070379 - 17 Jul 2023
Cited by 1 | Viewed by 2273
Abstract
A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers–Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic [...] Read more.
A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers–Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive–behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies. Full article
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11 pages, 1880 KiB  
Article
Cycle Threshold (Ct) Values of SARS-CoV-2 Detected with the GeneXpert® System and a Mutation Associated with Different Target Gene Failure
by Keita Yamashita, Terumi Taniguchi, Noriyasu Niizeki, Yuki Nagao, Akira Suzuki, Akihiro Toguchi, Shiori Takebayashi, Jinko Ishikawa, Osanori Nagura, Kazuki Furuhashi, Moriya Iwaizumi and Masato Maekawa
Curr. Issues Mol. Biol. 2023, 45(5), 4124-4134; https://doi.org/10.3390/cimb45050262 - 07 May 2023
Cited by 1 | Viewed by 2019
Abstract
SARS-CoV-2 nucleic acid detection tests enable rapid virus detection; however, it is challenging to identify genotypes to comprehend the local epidemiology and infection routes in real-time qRT-PCR. At the end of June 2022, our hospital experienced an in-hospital cluster of COVID-19. When examined [...] Read more.
SARS-CoV-2 nucleic acid detection tests enable rapid virus detection; however, it is challenging to identify genotypes to comprehend the local epidemiology and infection routes in real-time qRT-PCR. At the end of June 2022, our hospital experienced an in-hospital cluster of COVID-19. When examined using the GeneXpert® System, the cycle threshold (Ct) value of the N2 region of the nucleocapsid gene of SARS-CoV-2 was approximately 10 cycles higher than that of the envelope gene. Sanger sequencing revealed a G29179T mutation in the primer and probe binding sites. A review of past test results revealed differences in Ct values in 21 of 345 SARS-CoV-2-positive patients, of which 17 cases were cluster-related and 4 were not. Including these 21 cases, 36 cases in total were selected for whole-genome sequencing (WGS). The viral genomes in the cluster-related cases were identified as BA.2.10, and those in the non-cluster cases were closely related and classified as being downstream of BA.2.10 and other lineages. Although WGS can provide comprehensive information, its use is limited in various laboratory settings. A measurement platform reporting and comparing Ct values of different target genes can improve test accuracy, enhance our understanding of infection spread, and be applied to the quality control of reagents. Full article
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15 pages, 15512 KiB  
Article
Endogenous piRNAs Can Interact with the Omicron Variant of the SARS-CoV-2 Genome
by Aizhan Rakhmetullina, Aigul Akimniyazova, Togzhan Niyazova, Anna Pyrkova, Saltanat Kamenova, Aida Kondybayeva, Alma-Gul Ryskulova, Anatoliy Ivashchenko and Piotr Zielenkiewicz
Curr. Issues Mol. Biol. 2023, 45(4), 2950-2964; https://doi.org/10.3390/cimb45040193 - 03 Apr 2023
Viewed by 1451
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, can still infect populations in many countries around the globe. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and its ability to evade [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, can still infect populations in many countries around the globe. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and its ability to evade immunity necessitate a priority study of its properties in order to quickly create effective means of preventing its spread. The current research aimed to examine the in silico interaction between PIWI-interacting RNAs (piRNAs) and the SARS-CoV-2 genome (gRNA) to identify endogenous piRNAs and propose synthetic piRNAs with strong antiviral activity for drug development. This study used validated bioinformatic approaches regarding the interaction of more than eight million piRNAs with the SARS-CoV-2 genome. The piRNAs’ binding sites (BSs) in the 5′UTR were located with overlapping nucleotide sequences termed clusters of BSs. Several BSs clusters have been found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a, and nucleocapsid. Sixteen synthetic piRNAs that interact with gRNA have been proposed with free binding energy ranging from −170 kJ/mol to −175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2. Full article
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15 pages, 2779 KiB  
Article
Biomarker Profiles Associated with COVID-19 Severity and Mortality
by Silvia Sánchez-Díez, Carlos Gómez-Ollés, María-Jesús Cruz, Miquel de Homdedeu, David Espejo, Jaume Ferrer, Oriol Roca, Andrés Pacheco and Xavier Muñoz
Curr. Issues Mol. Biol. 2023, 45(3), 1998-2012; https://doi.org/10.3390/cimb45030128 - 01 Mar 2023
Cited by 1 | Viewed by 1383
Abstract
Introduction: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. Methods: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, [...] Read more.
Introduction: The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery. Methods: Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-ɣ, MCP-1, MIP-1β, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3. Results: At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 (p = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 (p = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC (p = 0.022 and p = 0.024, respectively) and FEV1 (p = 0.012 and p = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, p = 0.001). Conclusions: Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients. Full article
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12 pages, 1403 KiB  
Article
Clinical Investigation of Leukocyte DNA Damage in COVID-19 Patients
by Hasan Doğan, Aslı Kara, Erdem Çankaya, Eda Balkan, Muhammet Ali Gürbüz, Murat Kızılkaya and Merve Aykaç
Curr. Issues Mol. Biol. 2023, 45(2), 963-974; https://doi.org/10.3390/cimb45020062 - 19 Jan 2023
Viewed by 1571
Abstract
This prospective cross-sectional study aimed to evaluate leukocyte DNA damage in coronavirus disease (COVID-19) patients. In this study, 50 COVID-19-positive patients attending the Erzurum City Hospital Internal Medicine Outpatient Clinic and 42 control group patients were included. DNA damage was detected in living [...] Read more.
This prospective cross-sectional study aimed to evaluate leukocyte DNA damage in coronavirus disease (COVID-19) patients. In this study, 50 COVID-19-positive patients attending the Erzurum City Hospital Internal Medicine Outpatient Clinic and 42 control group patients were included. DNA damage was detected in living cells through leukocyte isolation in 50 COVID-19-positive patients using the comet assay method. DNA tail/head (olive) moments were evaluated and compared. White blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), neutrophils (NEU), lymphocytes (LYM), eosinophils (EO), monocytes (MONO), basophils (BASO), platelets (PLT), and the neutrophil/lymphocyte ratio (NLR) were analyzed. The RBC, lymphocyte, eosinophil, and monocyte means were significantly higher in the control group (p < 0.05), whereas the HGB and neutrophile means were significantly higher in the study group (p < 0.05). There were significant negative correlations between COVID-19 and RBC (r = −0.863), LYM (r = −0.542), EO (r = −0.686), and MONO (r = −0.385). Meanwhile, there were significant positive correlations between COVID-19 and HGB (r = 0.863), NEU (r = 0.307), tail moment (r = 0.598), and olive moment (r = 0.582). Both the tail and olive moment mean differences were significantly higher in the study group, with higher ranges (p < 0.05). COVID-19 infection caused statistically significant increases in both the tail and olive damage percentage in patients, causing DNA damage. Lastly, the NLR rate was associated with the presence and progression of COVID-19. Full article
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19 pages, 7572 KiB  
Article
Severe Acute Respiratory Syndrome Coronavirus-2 Delta Variant Study In Vitro and Vivo
by Hranush Avagyan, Sona Hakobyan, Arpine Poghosyan, Lina Hakobyan, Liana Abroyan, Elena Karalova, Aida Avetisyan, Mariam Sargsyan, Bagrat Baghdasaryan, Nane Bayramyan, Diana Avetyan and Zaven Karalyan
Curr. Issues Mol. Biol. 2023, 45(1), 249-267; https://doi.org/10.3390/cimb45010019 - 30 Dec 2022
Viewed by 1291
Abstract
At the end of 2019, an outbreak of a new severe acute respiratory syndrome caused by a coronavirus occurred in Wuhan, China, after which the virus spread around the world. Here, we have described the adaptive capacity and pathogenesis of the SARS-CoV-2 Delta [...] Read more.
At the end of 2019, an outbreak of a new severe acute respiratory syndrome caused by a coronavirus occurred in Wuhan, China, after which the virus spread around the world. Here, we have described the adaptive capacity and pathogenesis of the SARS-CoV-2 Delta variant, which is widespread in Armenia, in vitro and vivo on Syrian hamsters. We have studied the changes in the SARS-CoV-2genome using viral RNA sequencing during virus adaptation in vitro and in vivo. Our findings revealed that SARS-CoV-2 in Syrian hamsters causes a short-term pulmonary form of the disease, the first symptoms appear within 48 h after infection, reach 5–7 days after infection, and begin to disappear by 7–9 days after infection. The virus induces pathogenesis in the blood and bone marrow, which generally corresponds to the manifestation of the inflammatory process. The pulmonary form of the disease passes faster than changes in blood cells and bone marrow. Our data show that hamster organs do not undergo significant pathological changes in the Delta variant of SARS-CoV-2 infection. Full article
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15 pages, 2882 KiB  
Article
Development and Validation of ScriptTaq COVID PCR: An In-House Multiplex rRT-PCR for Low-Cost Detection
by Dana Abdalghani AbuObead, Tasnim Khalid Alhomsi, Mahmoud Zhra, Bandar Alosaimi, Muaawia Hamza, Maaweya Awadalla, Osama Ezzeldin Abdelhadi, Joud Abdullah Alsharif, Liliane Okdah, Khaled AlKattan, Saeed Al Turki, Hana M. A. Fakhoury and Ahmad Aljada
Curr. Issues Mol. Biol. 2022, 44(12), 6117-6131; https://doi.org/10.3390/cimb44120417 - 05 Dec 2022
Viewed by 2003
Abstract
The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 [...] Read more.
The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 infection (ScriptTaq COVID PCR). Furthermore, we describe two methods for RNA extraction using either an in-house silica column or silica-coated magnetic beads to replace commercial RNA extraction kits. Different buffer formulations for silica column and silica-coated magnetic beads were tested and used for RNA isolation. Taq polymerase enzyme and thermostable reverse transcriptase enzyme were purified from bacterial clones. Primers/probes sequences published by the WHO and CDC were used for the qualitative detection of the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes, respectively. ScriptTaq COVID PCR assay was able to detect up to 100 copies per reaction of the viral RdRP and N genes. The test demonstrated an overall agreement of 95.4%, a positive percent agreement (PPA) of 90.2%, and a negative percent agreement (NPA) of 100.0% when compared with two commercially available kits. ScriptTaq COVID PCR diagnostic test is a specific, sensitive, and low-cost alternative for low-resource settings. Full article
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Review

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18 pages, 1793 KiB  
Review
The Sphingolipid-Signaling Pathway as a Modulator of Infection by SARS-CoV-2
by Simona Fenizia, Melania Gaggini and Cristina Vassalle
Curr. Issues Mol. Biol. 2023, 45(10), 7956-7973; https://doi.org/10.3390/cimb45100503 - 28 Sep 2023
Cited by 2 | Viewed by 884
Abstract
Ceramides and other related sphingolipids, important cellular components linked to metabolic homeostasis and cardiometabolic diseases, have been found to be involved in different steps of the SARS-CoV-2 life cycle. Hence, changes in their physiological levels are identified as predictors of COVID-19 severity and [...] Read more.
Ceramides and other related sphingolipids, important cellular components linked to metabolic homeostasis and cardiometabolic diseases, have been found to be involved in different steps of the SARS-CoV-2 life cycle. Hence, changes in their physiological levels are identified as predictors of COVID-19 severity and prognosis, as well as potential therapeutic targets. In this review, an overview of the SARS-CoV-2 life cycle is given, followed by a description of the sphingolipid metabolism and its role in viral infection, with a particular focus on those steps required to finalize the viral life cycle. Furthermore, the use and development of pharmaceutical strategies to target sphingolipids to prevent and treat severe and long-term symptoms of infectious diseases, particularly COVID-19, are reviewed herein. Finally, research perspectives and current challenges in this research field are highlighted. Although many aspects of sphingolipid metabolism are not fully known, this review aims to highlight how the discovery and use of molecules targeting sphingolipids with reliable and selective properties may offer new therapeutic alternatives to infectious and other diseases, including COVID-19. Full article
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22 pages, 1332 KiB  
Review
Pathological Effects of SARS-CoV-2 Associated with Hematological Abnormalities
by Shama, Asif Mahmood, Shahid Mehmood and Wen Zhang
Curr. Issues Mol. Biol. 2023, 45(9), 7161-7182; https://doi.org/10.3390/cimb45090453 - 28 Aug 2023
Cited by 2 | Viewed by 1458
Abstract
The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to [...] Read more.
The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower respiratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse outcomes. Prophylactic anticoagulation is essential to prevent complications and death rates associated with the virus’s effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation (DIC) exhibits some similarities to DIC induced by sepsis. Lactate dehydrogenase (LDH), D-dimer, ferritin, and C-reactive protein (CRP) biomarkers often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19. Full article
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20 pages, 349 KiB  
Review
Host-Based Treatments for Severe COVID-19
by Lucrezia Mondini, Francesco Salton, Liliana Trotta, Chiara Bozzi, Riccardo Pozzan, Mariangela Barbieri, Stefano Tavano, Selene Lerda, Michael Hughes, Marco Confalonieri, Paola Confalonieri and Barbara Ruaro
Curr. Issues Mol. Biol. 2023, 45(4), 3102-3121; https://doi.org/10.3390/cimb45040203 - 05 Apr 2023
Cited by 3 | Viewed by 1456
Abstract
COVID-19 has been a global health problem since 2020. There are different spectrums of manifestation of this disease, ranging from asymptomatic to extremely severe forms requiring admission to intensive care units and life-support therapies, mainly due to severe pneumonia. The progressive understanding of [...] Read more.
COVID-19 has been a global health problem since 2020. There are different spectrums of manifestation of this disease, ranging from asymptomatic to extremely severe forms requiring admission to intensive care units and life-support therapies, mainly due to severe pneumonia. The progressive understanding of this disease has allowed researchers and clinicians to implement different therapeutic alternatives, depending on both the severity of clinical involvement and the causative molecular mechanism that has been progressively explored. In this review, we analysed the main therapeutic options available to date based on modulating the host inflammatory response to SARS-CoV-2 infection in patients with severe and critical illness. Although current guidelines are moving toward a personalised treatment approach titrated on the timing of presentation, disease severity, and laboratory parameters, future research is needed to identify additional biomarkers that can anticipate the disease course and guide targeted interventions on an individual basis. Full article
21 pages, 2282 KiB  
Review
Era of Molecular Diagnostics Techniques before and after the COVID-19 Pandemic
by Ahmad M. Alamri, Faris A. Alkhilaiwi and Najeeb Ullah Khan
Curr. Issues Mol. Biol. 2022, 44(10), 4769-4789; https://doi.org/10.3390/cimb44100325 - 11 Oct 2022
Cited by 3 | Viewed by 5257
Abstract
Despite the growth of molecular diagnosis from the era of Hippocrates, the emergence of COVID-19 is still remarkable. The previously used molecular techniques were not rapid enough to screen a vast population at home, in offices, and in hospitals. Additionally, these techniques were [...] Read more.
Despite the growth of molecular diagnosis from the era of Hippocrates, the emergence of COVID-19 is still remarkable. The previously used molecular techniques were not rapid enough to screen a vast population at home, in offices, and in hospitals. Additionally, these techniques were only available in advanced clinical laboratories.The pandemic outbreak enhanced the urgency of researchers and research and development companies to invent more rapid, robust, and portable devices and instruments to screen a vast community in a cost-effective and short time. There has been noteworthy progress in molecular diagnosing tools before and after the pandemic. This review focuses on the advancements in molecular diagnostic techniques before and after the emergence of COVID-19 and how the pandemic accelerated the implantation of molecular diagnostic techniques in most clinical laboratories towardbecoming routine tests. Full article
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Other

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8 pages, 2112 KiB  
Brief Report
Single-Cell RNA Sequencing Reveals Alterations in Patient Immune Cells with Pulmonary Long COVID-19 Complications
by Kristīne Vaivode, Rihards Saksis, Helēna Daiga Litvina, Helvijs Niedra, Marta Līva Spriņģe, Una Krūmiņa, Jānis Kloviņš and Vita Rovite
Curr. Issues Mol. Biol. 2024, 46(1), 461-468; https://doi.org/10.3390/cimb46010029 - 02 Jan 2024
Viewed by 954
Abstract
Since the emergence of the COVID-19 pandemic, the effects of SARS-CoV-2 have been extensively researched. While much is already known about the acute phase of the infection, increasing attention has turned to the prolonged symptoms experienced by a subset of individuals, commonly referred [...] Read more.
Since the emergence of the COVID-19 pandemic, the effects of SARS-CoV-2 have been extensively researched. While much is already known about the acute phase of the infection, increasing attention has turned to the prolonged symptoms experienced by a subset of individuals, commonly referred to as long COVID-19 patients. This study aims to delve deeper into the immune landscape of patients with prolonged symptoms by implementing single-cell mRNA analysis. A 71-year-old COVID-19 patient presenting with persistent viral pneumonia was recruited, and peripheral blood samples were taken at 3 and 2 years post-acute infection onset. Patients and control peripheral blood mononuclear cells (PBMCs) were isolated and single-cell sequenced. Immune cell population identification was carried out using the ScType script. Three months post-COVID-19 patients’ PBMCs contained a significantly larger immature neutrophil population compared to 2-year and control samples. However, the neutrophil balance shifted towards a more mature profile after 18 months. In addition, a notable increase in the CD8+ NKT-like cells could be observed in the 3-month patient sample as compared to the later one and control. The subsequent change in these cell populations over time may be an indicator of an ongoing failure to clear the SARS-CoV-2 infection and, thus, lead to chronic COVID-19 complications. Full article
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