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One of the symptoms of a new coronavirus infection (COVID-19) is a complete or partial violation of the sense of smell. The aim of the work is to analyze the published results of scientific research on the mechanisms of olfactory impairment in COVID-19. Material and methods. Research was conducted for publications in Pubmed on the problem of olfactory impairment in COVID-19 using terms indexed by MeSH. The systematic review was compiled in accordance with the checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Results. Publication's analysis has shown that the existing ideas about conductive anosmia are insufficient to explain the causes of olfactory impairment caused by SARS-CoV-2. It has been established that ACE2 and TMPRSS2 receptors located on the surface of target cells are necessary for the penetration of a new coronavirus. It is known that these receptors are mainly located on the cells of the olfactory epithelium. The main hypothesis of olfactory impairment in COVID-19 is that anosmia/hyposmia is caused by damage not to neuronal cells (as previously assumed), but to the olfactory epithelium. There is no confirmation of the point of view about the damage of SARS-CoV-2 olfactory bulbs and olfactory neurons, since they do not express receptor proteins for the virus on their surface.Copyright © 2022 by the authors.
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Background: SARS CoV 2 infection alters the immunological profiles of natural killer (NK) cells. However, whether NK anti-viral functions (direct cytotoxicity and/or antibody-dependent cell cytotoxicity (ADCC)) are impaired during severe COVID-19 and what host factors modulate these functions remain unclear. Method(s): Using functional assays, we examined the ability of NK cells from SARS-CoV-2 negative controls (n=12), mild COVID-19 patients (n=26), and hospitalized COVID-19 patients (n=41) to elicit direct cytotoxicity and ADCC [NK degranulation by flow] against cells expressing SARS-CoV-2 antigens. SARS-CoV- 2 N antigen plasma load was measured using an ultra-sensitive Simoa assay. We also phenotypically characterized the baseline expression of NK activating (CD16 and NKG2C), maturation (CD57), and inhibitory (NKG2A and the glyco-immune negative checkpoint Siglec-9) by flow cytometry. Finally, an anti-Siglec-9 blocking antibody was used to examine the impact of Siglec-9 expression on anti-SARS-CoV-2-specific ADCC [degranulation and target cell lysis]. Result(s): NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2-antigen-expressing cells (in direct cytolytic and ADCC assays) than did cells from mild COVID-19 patients or negative controls (Fig. 1A). The lower NK degranulation was associated with higher plasma levels of SARS-CoV-2 N-antigen (P<=0.02). Phenotypic and functional analyses showed that NK cells expressing Siglec-9 elicited higher ADCC than Siglec-9- NK cells (P<0.05;Fig. 1B). Consistently, Siglec-9+ NK cells expressed an activated and mature phenotype with higher expression of CD16, CD57, and NKG2C, and lower expression of NKG2A, than Siglec-9- NK cells (P<=0.03). These data are consistent with the concept that the NK cell subpopulation expressing Siglec-9 is highly activated and cytotoxic. However, the Siglec-9 molecule itself is an inhibitory receptor that restrains NK cytotoxicity during cancer and other infections. Indeed, blocking Siglec-9 significantly enhanced the ADCC-mediated NK degranulation and lysis of SARS-CoV-2-antigen-positive target cells (P<=0.05;Fig. 1C). Conclusion(s): These data support a model (Fig. 1D) in which the Siglec-9+ CD56dim NK subpopulation is cytotoxic even while being restrained by the inhibitory effects of Siglec-9. However, alleviating the Siglec-9-mediated restriction on NK cytotoxicity can further improve NK immune surveillance and presents an opportunity to develop novel immunotherapeutic tools against SARS-CoV-2 infected cells. (Figure Presented).
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Acute pancreatic pseudocysts are increasingly recognized as complications in patients with coronavirus disease 2019 (COVID-19). There-fore, it is important for healthcare providers to be aware of this phenomenon to ensure proper diagnosis and treatment. Up to 17% of patients with severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) infection have been shown to develop pancreatic lesions. These pancreatic lesions can be caused directly by the cytopathic effects of the viral infection or indirectly by systemic responses to inflammation or respiratory failure. Several studies have shown that angio-tensin-converting enzyme 2 (ACE2) is the functional receptor used by SARS-CoV-2 to gain access to target cells, while ACE2 receptors are expressed in significant amounts in the pancreas. In this article, we present 2 cases of COVID-19. patients that presented with similar pancreatic lesions. The first case was a 47-year-old lady who presented to the emergency department (ED) with flu-like symptoms for ten days. Incidental findings on computed tomography (CT) scan showed a large, multiloculated cystic mass in the pancreatic tail. The second case was an 81-year-old Caucasian lady who presented to the outpatient clinic with multiple chronic complaints after an acute COVID-19 infection four months prior. Abdominal CT scan with oral contrast revealed multiple hypodense masses on the pancreas measuring 0.3 cm in diameter. The cases we reported in this article showed the degree of COVID-19's effect on the gastrointestinal system, with pancreatic injury occurring during the early phases of the acute phase of the infection and lasting up to 4 months post-resolution of the infection.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.
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Background: A 5-day course of nirmatrelvir-ritonavir (N/R) can significantly reduce the hospitalization and death rates and the duration of infectiousness in high-risk SARS-CoV-2 patients. However, in a fraction of treated individuals virus rebounds following an initial recovery after treatment. The mechanism driving rebound is not well understood. We hypothesize that treatment with N/R near the time of symptom onset halts the depletion of target cells, but does not fully eliminate the virus, and thus can lead to viral rebound. Method(s): Previously, we and others have developed viral dynamic models and successfully used them to fit data on SARS-CoV-2 infection. Here we expand these models and incorporate N/R pharmacokinetic and pharmacodynamic effects and an adaptive immune response. Result(s): We fit this model to the data presented in Charness et al., NEJM (2022) where longitudinal quantitative PCR data is available for 3 individuals who experienced viral rebounds after taking N/R. We found that the model fit the data well. By varying model parameters from their best-fit values, we show the occurrence of viral rebound is sensitive to model parameters, and the time treatment is initiated, which may explain why only a fraction of individuals rebound. Finally, the model with its best-fit parameter values was used to test the therapeutic effects of treatment extended to 10 days or a second 5-day course of N/R initiated one day after symptoms reoccur. Conclusion(s): Our model fits predicted that virus is not fully eliminated during N/R treatment and supported our initial hypothesis that at the end of treatment target cells are available to allow viral resurgence. Simulating the effect of starting treatment later, we find the probability of viral rebound occurring decreases, suggesting that delaying treatment may be a strategy to reduce viral rebound. However, N/R treatment accelerates viral clearance and hence potentially can reduce viral transmission. Thus, delaying treatment may have a detrimental effect on public health and could also have impact on the severity of disease in the high-risk patients for whom N/R is recommended. Increasing treatment from 5 to 10 days continues to preserve target cells and thus may still allow viral rebound if viable virus is present at the end of treatment and sufficient adaptive immunity has not developed. Simulating giving a second course of treatment one day after symptoms reappear, did not prevent rebound.
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The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.
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Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2-4 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells - basophiles and eosinophils - were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased "regulatory" Tfh1 cell and increased "pro-inflammatory" Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of "naive" and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24- plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
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The coronaviruses, belonging to the family Coronaviridae, have caused a massive pandemic in December 2019 after their previous outbreaks as SARS-CoV and MERS. The outbreak is believed to have originated from the seafood and live market in the Hubei province of China. The Rhinolophus species are the natural hosts of this virus. This virus caused pneumonia and took away many lives be-fore it was recognized as the novel Coronavirus. Very little information is available about the biology and nature of the novel Coronavirus. This article reviews multiple aspects encompassing its origin, epi-demiology, pathogenesis, symptoms, and the global statistics of spread. Acute respiratory distress syndrome (ARDS) is the key symptom of this condition. Angiotensin-converting enzyme 2 (ACE2) helps in the penetration of the virus into the target cells. Deeper research and understanding are essential for the identification of antibodies that inhibit ACE2 and can prevent viral replication. Drug design and control of disease are crucial. In countries like India, where plant diversity is extensive, it is prudent to focus on plant-based alternative drugs. Many attempts have been made to review and curate the drug discovery attempts using immuno-informatic and bioinformatic tools.Copyright © 2021 Bentham Science Publishers.
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In December 2019, a new severe acute respiratory coronavirus (SARS-COV-2) had caused outbreaks of pneumonia in Wuhan city, China. It was known as coronavirus infected dis-ease-2019 (COVID-19). COVID-19 patients typically have a fever and respiratory syndrome, where the lung is the main target organ affected by this virus. The objective of this review is to monitor and evaluate injuries caused by the SARS-COV-2 virus on multiple organs other than the lung as the gastrointestinal tract, liver, kidney, heart, ovary, ocular, olfactory, gonad, skin, central nervous system, and sense organs. As SARS-COV-2 virus enters host cells via cell receptor an-giotensin circulating enzyme-2 (ACE2), so it is important to identify the main target cells attacked by SARS-COV-2 virus by comparing the ACE2 expression and viral upload in different organs. In conclusion, the definite role of body organs is explored in the manifestation of COVID-19 infection and crosstalk between other organs are useful tools to find any correlation between disease severity and organs dysfunction, exact prognosis, disease prevention measures, clinical care, and treatment strategies.Copyright © 2021 Bentham Science Publishers.
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Introduction: The World Health Organization (WHO) has recently declared the outbreak and spread of the new strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS--CoV-2) a global pandemic. In this regard, a lot of scientific investigations and clinical trials on some existing antiviral and antibiotic drugs have been ongoing to combat this menace. Method(s): In the past, conventional drug therapy has shown irregular drug distribution, poor solubil-ity, and low permeability to target cells, organs, and tissues. However, Chloroquine, Hydrox-ychloroquine Remdesivir, Lopinavir/Ritonavir, etc. have attracted several investigations in mono-therapeutic approaches and a combination of therapy have shown promising effects in reducing viral loading in some SARS-CoV-2 infected patients. Nevertheless, the advent of nanomedicine has triggered serious attention on drug-loaded nanoparticle as nanocarriers to deliver bioactive drug molecules to target organs with increased circulation and controlled release. Therefore, the application of nanoparticles as nanocarriers for the controlled release of antiviral drugs would improve the ease of drug administration and care of patients admitted at various health care facilities world-wide. Conclusion(s): Owing to their small sizes, biocompatibility, and high encapsulation properties, nano-particles can be utilized as potential nanocarrier of antiviral drugs for the SARS-CoV-2 management at a reduced cost with minimal side effect in the body system. In addition, some noticeable concerns on the ongoing management of SARS-CoV-2 pandemic in developing nations have been presented for concerted attention.Copyright © 2021 Bentham Science Publishers.
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Vaccines are one of the most effective means of preventing viral infections. Since Edward Jenner invented the world's first vaccine in 1796, against smallpox, various types of vaccine have been DDS developed, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, viral vector vaccines and nucleic acid vaccines. Viral vector vaccines and nucleic acid vaccines (mRNA vaccines and DNA vaccines)have been developed most recently. In these vaccines, genes encoding viral proteins that serve as antigens are introduced into the body. The viral vector is an excellent vaccine delivery system that efficiently delivers antigen genes to target cells, and has been utilized for vaccine development against a variety of emerging infectious diseases, including AIDS, malaria, Ebola hemorrhagic fever, dengue fever, and most recently COVID-19 . Here, we provide an overview of viral vector vaccines and discuss recent efforts to develop vaccines against emerging infectious diseases.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.
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Vaccines are one of the most effective means of preventing viral infections. Since Edward Jenner invented the world's first vaccine in 1796, against smallpox, various types of vaccine have been DDS developed, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, viral vector vaccines and nucleic acid vaccines. Viral vector vaccines and nucleic acid vaccines (mRNA vaccines and DNA vaccines)have been developed most recently. In these vaccines, genes encoding viral proteins that serve as antigens are introduced into the body. The viral vector is an excellent vaccine delivery system that efficiently delivers antigen genes to target cells, and has been utilized for vaccine development against a variety of emerging infectious diseases, including AIDS, malaria, Ebola hemorrhagic fever, dengue fever, and most recently COVID-19 . Here, we provide an overview of viral vector vaccines and discuss recent efforts to develop vaccines against emerging infectious diseases.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.
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Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147 (CD147) receptors based on SNAP-tag technology provides a comprehensive solution for screening multiple components in complex samples acting on the two receptors. The selectivity and applicability of the system were validated with encouraging results. Under the optimized conditions, this method was used to screen for antiviral components in Citrus aurantium extracts. The results showed that 25 µmol /L of the active ingredient could inhibit virus entry into cells. Hesperidin, neohesperidin, nobiletin, and tangeretin were identified as antiviral components. In vitro pseudovirus assays and macromolecular cell membrane chromatography further verified the interaction of these four components with host-virus receptors, showing good effects on some or all of the pseudoviruses and host receptors. In conclusion, the in-line dual-targeted cell membrane chromatography LC-MS system developed in this study can be used for the comprehensive screening of antiviral components in complex samples. It also provides new insight into small-molecule drug-receptor and macromolecular-protein-receptor interactions.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2 , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Cell Membrane/metabolism , Antiviral Agents/pharmacologyABSTRACT
Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2–4 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells — basophiles and eosinophils — were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased "regulatory” Tfh1 cell and increased "pro-inflammatory” Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of "naïve” and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24– plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.
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Researches aimed at finding effective means of pathogenic therapy for this viral infection are extremely relevant. Researches of the last three years have established that some human pathogenic coronaviruses - MERS, SARS-CoV and SARS-CoV-2, contain aliphatic polyamines in their structure, which participate in the packaging of genetic material (DNA, RNA), as well as the nucleocapsid. Virus-host cell interactions also provide adhesion processes on the surface of the cytoplasmic membrane of target cells. In the intra-cellular space, aliphatic polyamines actively affect the translation and replication processes of the genetic material and necessary proteins of the virus itself, as well as the formation of daughter viruses. Long-term persistence in the SARS-CoV-2 infected organism is largely due to the absorption of polyamines by corona-virus localized in target cells of the blood and parenchymatous organs. Unfortunately, the above new facts did not serve as a prerequisite for finding effective means of pathogenetic therapy for COVID-19, based on the inhibition of polyamine-dependent processes that ensure long-term persistence of SARS-CoV-2 in the infected organism. We are talking about specific drugs such as alpha-difluoromethylornithine and its ana-logues, which are successfully used in oncology in the complex treatment of malignant neoplasms with the aim of lowering the level of aliphatic polyamines in the affected areas of malignantly transformed organs. We recommend the use of polyamine-free and polyamine-deficient diets for COVID-19 for the first time. In the planned study, we will present tables with food products of animal and vegetable origin, characterized by extremely low content and/or absence of aliphatic polyamines in them. At the same time, food products with a high content of aliphatic polyamines should be excluded from the general list of products recommended for COVID-19 patients. We also recommend the use of a polyamine-deficient diet (with a preventive purpose) during the COVID-19 pandemic to a wide contingent of practically healthy individuals, convalescents, medical staff of specialized infectious disease clinics, as well as family members of SARS-CoV-2 infected patients. Copyright © 2022, Yerevan State Medical University. All rights reserved.
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SESSION TITLE: Management of COVID-19-Induced Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Up to 17% of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to develop pancreatic lesions (1). We present 2 cases of coronavirus disease 2019 (COVID-19) patients that presented with pancreatic lesions. CASE PRESENTATION: Case1 A 47-year-old lady with a history of type 2 diabetes mellitus present to the emergency department (ED) with complaints of flu-like symptoms for ten days. She tested positive for COVID-19 by rapid PCR. Computed tomography (CT) scan without contrast on admission shows an incidental finding of a pancreatic mass (see Figure 1). Abdominal CT with contrast shows a large, multiloculated cystic mass in the pancreatic tail (see Figure 2). Laboratory examination depicted lipase: 27 U/L, CA19-9: 72 U/mL, CEA: 6.5 ng/mL, CA125: 24 U/mL, erythrocyte sedimentation rate (ESR):2 mm/h, Total Bilirubin: 0.6 mg/dl, Direct Bilirubin: 0.1 mg/dl. Following treatment, the patient recovered fully and is discharged from the hospital 10 days later with home oxygen therapy. Case2 An 81-year old Caucasian lady presented to the outpatient clinic with complaints of fecal incontinence. She tested positive for COVID-19, four months before her visit. CT scan of the abdomen with oral contrast revealed multiple hypodense masses on the pancreas measuring 0.3cm in diameter (see Figure 3). Laboratory tests reveal CA19-9: 57 U/mL, CA125: 8 U/mL, CEA: 1.9 ng/mL, erythrocyte sedimentation rate (ESR):11 mm/h, C-reactive protein: 0.7 mg/L, Total Bilirubin: 1.5 mg/dl, Direct Bilirubin: 1.3 mg/dl. Following outpatient treatment and follow-up, the patient's symptoms were relieved. DISCUSSION: Pancreatic lesions in COVID-19 patients can be caused directly by the cytopathic effects of the viral infection, or indirectly by systemic responses to inflammation or respiratory failure. Several studies have shown that ACE2 is the functional receptor used by SARS-CoV-2 to gain access to target cells (2) and ACE-2 receptors are expressed in significant amounts in the pancreas (3). In the first case, an incidental finding of a multi-cystic pancreatic mass on admission was reported. There was no pancreatic ductal dilation on the CT scan, which may indicate a direct injury caused by cytopathic effects of the virus rather than inflammation resulting in exocrine secretions forming cysts. In the second case, multiple masses on the pancreas were found after recovering from COVID-19. These lesions could be remnants of a previous pancreatic injury during the acute phase of the infection. CONCLUSIONS: COVID-19 infection may trigger pancreatic injury in some patients. Reference #1: Yong, Shin Jie. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infectious diseases. 2021 Oct;53(10): 737–754. Reference #2: Ma C, Cong Y, Zhang H. COVID-19, and the Digestive System. Vol. 115, American Journal of Gastroenterology. Wolters Kluwer Health;2020. p. 1003–6. Reference #3: Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z. ACE2 Expression in Pancreatic Damage After SAERS-CoV-2 Infection. Gastroenterology. 2020 Aug 1;18(9): 2128 – 2130.e2. DISCLOSURES: No relevant relationships by Ailine Canete Cruz No relevant relationships by Claudia Ramirez No relevant relationships by Joseph Varon No relevant relationships by Mohamed Ziad
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SESSION TITLE: Biological Markers in Patients with COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: C-REACTIVE PROTEIN (CRP) is an acute phase reactant produced by liver in response to cytokines especially Interleukin-6 (IL-6). CRP consists of five identical subunits arranged symmetrically around a central pore. CRP binds to phospholipid constituents of foreign pathogens and damaged cells to promote the elimination of pathogens and clearance of apoptotic cells. Covid 19 virus through the spike protein binds to Angiotensin Converting Enzyme 2 receptors of host target cells, particularly receptors of alveolar Type 2 epithelial cells. This reaction causes Cytokine storm syndrome with release of several cytokines including IL-6. The purpose of this study is to assess the significance of CRP levels in predicting mortality of Covid 19 infection induced Adult Respiratory Distress syndrome (ARDS) patients admitted in the Intensive Care Unit (ICU). METHODS: We retrospectively reviewed the records of covid 19 induced ARDS patients admitted to ICU between July 1st 2020 and June 30th 2021 in a community hospital. We collected the CRP level on admission and discharge (survived or deceased) during that admission. The discharge CRP level was subtracted from admission CRP level. The positive value was taken as elevated CRP level and negative value was taken as non-elevated CRP. RESULTS: A total of 484 covid patients were admitted at the ICU during that period. Of those, 228 patients had admission and discharge (survived or deceased) CRP lab value available. 177 patients survived with 33 (18.6%) had elevated CRP and 144 (81.4%) had non-elevated CRP levels. 51 patients deceased with 32 (62.7%) had elevated CRP and 10 (37.3%) had non-elevated CRP levels. The p-value is <.00001. CONCLUSIONS: Elevated CRP was associated with high ICU mortality in Covid 19 infected ARDS patients. CLINICAL IMPLICATIONS: CRP can be elevated initially due to Cytokine storm syndrome and later may be related to secondary infection especially with immunosuppressive treatment. Elevated CRP levels indicates higher inflammatory response which should prompt early appropriate intervention. DISCLOSURES: No relevant relationships by Ravi Chandran No relevant relationships by Pranav Vadhul
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mRNA vaccines open promising avenues for overcoming a variety of diseases due to their high therapeutic utilities, rapid growth capacities, and safe administration potentials. With the emergence of COVID-19, the use of mRNA vaccines has become even more widespread and far-reaching. However, for mRNA to be delivered to target cells and tissues, several obstacles must be overcome. For instance, naked mRNAs get easily and hastily degraded by ribonucleases in tissues and the bloodstream, and since mRNAs are large and polyanionic molecules, they cannot passively diffuse across cell membranes. Even though mRNAs are internalized by APCs, they must be able to reach the cytoplasm and escape endo-lysosomal traffic. Therefore, distinctive transport systems for efficient encapsulation of mRNAs using nanocarrier systems are required to ensure their delivery to cells’ cytoplasm. At this point, non-viral gene delivery systems such as polymers and lipids come to the fore, in which they can overcome the biological barriers and provide efficient delivery of mRNAs. Recently, mRNA vaccines have been used as a powerful weapon against COVID-19 pandemic which has affected the whole world since December 2019. This was clear by the emergence of Pfizer-BioNTech and Moderna vaccines, which offered mRNA vaccines with auspicious treatment abilities. A variety of carrying candidates have been utilized in such vaccines as polymers, metal nanoparticles, as well as LNPs, which each comes with its cons and pros in delivering mRNA. All of these mentioned points will be clarified and discussed in detail in this review paper.
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Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.
Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Humans , Spike Glycoprotein, CoronavirusABSTRACT
Background: Patients with autoimmune systemic diseases have an increased risk to contract infections and develop severe complications;infections in turn can reactivated and worsen the disease itself in a vicious circle. Thus, vaccination is the main weapon to prevent infectious diseases and represents an important and safe instrument of care for rheumatic patients that needs to be further promoted. However, the immunosuppressive drugs used to treat rheumatic diseases may impair response to vaccines, in particular those targeting B or T cells directly (1). Objectives: The aim of this study is to evaluate the B and T-cell mediated immune response to mRNA vaccination in patients with systemic autoimmune diseases, such as vasculitis or systemic connective tissue diseases, early or continuously treated with B-cell targeting therapies, rituximab (RTX) or beli-mumab (BEL), by comparing with controls and each other. Secondary we evaluated the in vitro effective neutralizing capacity in belimumab-exposed patients. Methods: Twenty-eight consecutive patients under treatment with rituximab (RTX, n=11) or belimumab (BEL, n=17) and 13 age/sex matched controls (non-rheumatic healthcare personnel) were enrolled in the study. Nobody presented anti-SARS-CoV2 antibodies related to previous viral contact and all were always negative at the molecular swab monthly control. All patients and controls received mRNA vaccines and were tested three to four weeks after complete vaccination. All RTX patients started vaccination within 5 months from the last infusion, and all but one of them were B-cell depleted. Anti-SARS-CoV-2 RBD total antibodies were analysed by a diagnostic assay (Elecsys, Roche) while T-cell response was evaluated using the IGRA test (Euroimmun). A subgroup of BEL-patients was tested with pseudovirus neutralization assay. Results: Detectable anti-SARS-CoV2 RBD antibodies were documented in 1/11 RTX patients versus 16/17 BEL patients (p<0.0001). The median concentration was signifcantly lower than that observed in controls (39.6 AU/ml vs 1133 AU/ml, p<0.0001). A very low titer of anti-RBD antibodies were documented only in 1 out of 11 patients in the RTX subgroup (0.93 U/ml, positive if >0,79 U/ml) and the patient was the only one who showed an initial B-cell recovery (CD19+ B-cell 5 cells/microL). Anti-RBD antibodies were documented in 16 out 17 of patients in the BEL subgroup. The median anti-RBD antibody titer in patients receiving BEL was 243 [77.55-744.0] U/ml, and it was signifcantly lower compared to the controls (p=0.002). The IGRA test was positive in 8/11 (72.7%) RTX patients vs 16/17 (94.1%) BEL patients (p=0.7), with interferon release comparable to control subjects (p=0.2). Six patients with BEL were also stratifed according to total antibodies (IgG+I-gA+IgM) against-RBD into high responders (>800 AU/mL, n=3) and low responders (≤45 AU/mL, n=3) and tested with pseudovirus neutralization assay. Two thirds of low titer group of patients neutralized the Wuhan-Hu1 strain at medium-low titer (IC50 ≈102) but were almost ineffective in inhibiting the B.1.1.7 entry into target cells (IC50 =10). Regarding high responders, while two patients were able to inhibit both the strains at medium-high titer (approximately IC50 ≈103 for Wuhan-Hu1 and B.1.1.7), one patient neutralized only the WT strain. Conclusion: B-cell targeting therapies do not preclude SARS-CoV-2 vaccination since a cellular immunity can raise even in the absence of circulating B cells. Most importantly, the immunogenicity of COVID-19 vaccination in SLE patients treated with belimumab is supported. However, patients showing the lowest humoral response to vaccine could remain at higher risk of infections, due to low neutralizing capacity.
ABSTRACT
Presence of SARS-CoV-2, the virus responsible for COVID-19, has been reported in numerous organs and tissues of infected patients, including the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood. While cases of intrauterine transmission between expectant mother and fetus have been documented, the impact of SARS-CoV-2 infection on early embryogenesis and establishment of a pregnancy are not known. This prompted us to ask if SARS-CoV-2 can infect embryos, since such an event could impact embryo viability and affect a subsequent pregnancy. We used a three-pronged approach to investigate this possibility: 1) Using RNA-seq and immunofluorescence, we learned that ACE2 and TMPRSS2, two factors required on target cells for SARS-CoV-2 entry, are coexpressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos;2) Using fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, we observed robust infection of trophectoderm cells, and this permissiveness could be attenuated with blocking antibodies targeting S or ACE2;and 3) Exposing human blastocysts to live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.