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1.
Rev Med Virol ; 31(6): e2236, 2021 11.
Article in English | MEDLINE | ID: covidwho-1573896

ABSTRACT

Modifications in HLA-I expression are found in many viral diseases. They represent one of the immune evasion strategies most widely used by viruses to block antigen presentation and NK cell response, and SARS-CoV-2 is no exception. These alterations result from a combination of virus-specific factors, genetically encoded mechanisms, and the status of host defences and range from loss or upregulation of HLA-I molecules to selective increases of HLA-I alleles. In this review, I will first analyse characteristic features of altered HLA-I expression found in SARS-CoV-2. I will then discuss the potential factors underlying these defects, focussing on HLA-E and class-I-related (like) molecules and their receptors, the most documented HLA-I alterations. I will also draw attention to potential differences between cells transfected to express viral proteins and those presented as part of authentic infection. Consideration of these factors and others affecting HLA-I expression may provide us with improved possibilities for research into cellular immunity against viral variants.


Subject(s)
Antigenic Variation , COVID-19/immunology , Clonal Anergy , Histocompatibility Antigens Class I/immunology , Immune Evasion , SARS-CoV-2/genetics , Alleles , COVID-19/pathology , COVID-19/virology , Cytokines/genetics , Cytokines/immunology , Cytotoxicity, Immunologic , Gene Expression , Histocompatibility Antigens Class I/genetics , Humans , Immunity, Cellular , Killer Cells, Natural/immunology , Killer Cells, Natural/virology , NK Cell Lectin-Like Receptor Subfamily C/genetics , NK Cell Lectin-Like Receptor Subfamily C/immunology , NK Cell Lectin-Like Receptor Subfamily D/genetics , NK Cell Lectin-Like Receptor Subfamily D/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/virology
2.
Mini Rev Med Chem ; 21(17): 2530-2543, 2021.
Article in English | MEDLINE | ID: covidwho-1504184

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering have led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials, researchers worldwide are currently using available conventional therapeutic drugs with the potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to showed promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID- 19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , SARS-CoV-2/drug effects , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/adverse effects , Alanine/pharmacology , Alanine/therapeutic use , Animals , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Humans , Randomized Controlled Trials as Topic
3.
J Virol ; 95(17): e0080721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1486516

ABSTRACT

The membrane fusion between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host cells is essential for the initial step of infection; therefore, the host cell membrane components, including sphingolipids, influence the viral infection. We assessed several inhibitors of the enzymes pertaining to sphingolipid metabolism, against SARS-CoV-2 spike protein (S)-mediated cell-cell fusion and viral infection. N-(4-Hydroxyphenyl) retinamide (4-HPR), an inhibitor of dihydroceramide Δ4-desaturase 1 (DES1), suppressed cell-cell fusion and viral infection. The analysis of sphingolipid levels revealed that the inhibition efficiencies of cell-cell fusion and viral infection in 4-HPR-treated cells were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids. We investigated the relationship of DES1 with the inhibition efficiencies of cell-cell fusion. The changes in the sphingolipid profile induced by 4-HPR were mitigated by the supplementation with exogenous cell-permeative ceramide; however, the reduced cell-cell fusion could not be reversed. The efficiency of cell-cell fusion in DES1 knockout (KO) cells was at a level comparable to that in wild-type (WT) cells; however, the ratio of saturated sphinganine-based lipids to the total sphingolipids was higher in DES1 KO cells than in WT cells. 4-HPR reduced cell membrane fluidity without any significant effects on the expression or localization of angiotensin-converting enzyme 2, the SARS-CoV-2 receptor. Therefore, 4-HPR suppresses SARS-CoV-2 S-mediated membrane fusion through a DES1-independent mechanism, and this decrease in membrane fluidity induced by 4-HPR could be the major cause for the inhibition of SARS-CoV-2 infection. IMPORTANCE Sphingolipids could play an important role in SARS-CoV-2 S-mediated membrane fusion with host cells. We studied the cell-cell fusion using SARS-CoV-2 S-expressing cells and sphingolipid-manipulated target cells, with an inhibitor of the sphingolipid metabolism. 4-HPR (also known as fenretinide) is an inhibitor of DES1, and it exhibits antitumor activity and suppresses cell-cell fusion and viral infection. 4-HPR suppresses membrane fusion through a decrease in membrane fluidity, which could possibly be the cause for the inhibition of SARS-CoV-2 infection. There is accumulating clinical data on the safety of 4-HPR. Therefore, it could be a potential candidate drug against COVID-19.


Subject(s)
Cell Membrane/metabolism , Fenretinide/pharmacology , Membrane Fluidity/drug effects , Oxidoreductases/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Cell Fusion , Cell Membrane/genetics , Gene Knockout Techniques , HEK293 Cells , Humans , Membrane Fluidity/genetics , Oxidoreductases/deficiency , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
5.
Rev Esp Quimioter ; 33(6): 444-447, 2020 Dec.
Article in Spanish | MEDLINE | ID: covidwho-1390020

ABSTRACT

OBJECTIVE: Co-circulation of the two Influenza B lineages hinders forecast of strain to include in trivalent vaccine. Autonomous Communities such as Cantabria continue without supplying tetravalent vaccine. The aim of this study was to analyse epidemiological characteristics of influenza type B in Cantabria (2019-2020 season) as well as to establish the predominant lineage and its relation to the recommended vaccine. METHODS: Retrospective study whereby flu diagnosis and lineage analysis were determined by RT-PCR. RESULTS: All samples belonged to the Victoria lineage. Most prevalent viral co-infection was due to SARS-CoV-2. The population affected by influenza B was mainly paediatric and non-vaccinated patients more frequently required hospital admittance. CONCLUSIONS: Influenza type B has a higher incidence in the paediatric population and type A affects more the adult population. Only 28.8% of patients with Influenza B that presented with some underlying condition or risk factor were vaccinated. This shows the need to increase coverage with tetravalent vaccines in order to reduce the burden of disease associated with the Influenza B virus.


Subject(s)
COVID-19/epidemiology , Influenza B virus , Influenza, Human/epidemiology , Pandemics , SARS-CoV-2 , Adult , COVID-19/virology , Chi-Square Distribution , Child , Coinfection/epidemiology , Coinfection/virology , Epidemics , Female , Hospitalization/statistics & numerical data , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Influenza, Human/virology , Male , Retrospective Studies , Seasons , Spain/epidemiology , Statistics, Nonparametric
6.
Viruses ; 13(1)2020 12 30.
Article in English | MEDLINE | ID: covidwho-1389523

ABSTRACT

SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-ß) production. N protein repressed IFN-ß production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-ß production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-ß response through targeting the initial step, potentially the cellular PRR-RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-ß production by interfering with RIG-I.


Subject(s)
COVID-19/immunology , DEAD Box Protein 58/metabolism , Interferon-beta/metabolism , Nucleocapsid Proteins/metabolism , SARS-CoV-2/metabolism , A549 Cells , Animals , DEAD Box Protein 58/genetics , HEK293 Cells , HeLa Cells , Host-Pathogen Interactions/immunology , Humans , Protein Interaction Domains and Motifs , Receptors, Immunologic , Signal Transduction
7.
Eur J Clin Pharmacol ; 76(11): 1615-1618, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1384377

ABSTRACT

AIM: SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases. SUBJECT AND METHOD: Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection. RESULTS: Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value. CONCLUSION: In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Betacoronavirus , COVID-19 , Drug Therapy, Combination , Humans , Inflammation/drug therapy , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Pandemics , SARS-CoV-2
8.
J Virol ; 95(17): e0080721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1381151

ABSTRACT

The membrane fusion between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host cells is essential for the initial step of infection; therefore, the host cell membrane components, including sphingolipids, influence the viral infection. We assessed several inhibitors of the enzymes pertaining to sphingolipid metabolism, against SARS-CoV-2 spike protein (S)-mediated cell-cell fusion and viral infection. N-(4-Hydroxyphenyl) retinamide (4-HPR), an inhibitor of dihydroceramide Δ4-desaturase 1 (DES1), suppressed cell-cell fusion and viral infection. The analysis of sphingolipid levels revealed that the inhibition efficiencies of cell-cell fusion and viral infection in 4-HPR-treated cells were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids. We investigated the relationship of DES1 with the inhibition efficiencies of cell-cell fusion. The changes in the sphingolipid profile induced by 4-HPR were mitigated by the supplementation with exogenous cell-permeative ceramide; however, the reduced cell-cell fusion could not be reversed. The efficiency of cell-cell fusion in DES1 knockout (KO) cells was at a level comparable to that in wild-type (WT) cells; however, the ratio of saturated sphinganine-based lipids to the total sphingolipids was higher in DES1 KO cells than in WT cells. 4-HPR reduced cell membrane fluidity without any significant effects on the expression or localization of angiotensin-converting enzyme 2, the SARS-CoV-2 receptor. Therefore, 4-HPR suppresses SARS-CoV-2 S-mediated membrane fusion through a DES1-independent mechanism, and this decrease in membrane fluidity induced by 4-HPR could be the major cause for the inhibition of SARS-CoV-2 infection. IMPORTANCE Sphingolipids could play an important role in SARS-CoV-2 S-mediated membrane fusion with host cells. We studied the cell-cell fusion using SARS-CoV-2 S-expressing cells and sphingolipid-manipulated target cells, with an inhibitor of the sphingolipid metabolism. 4-HPR (also known as fenretinide) is an inhibitor of DES1, and it exhibits antitumor activity and suppresses cell-cell fusion and viral infection. 4-HPR suppresses membrane fusion through a decrease in membrane fluidity, which could possibly be the cause for the inhibition of SARS-CoV-2 infection. There is accumulating clinical data on the safety of 4-HPR. Therefore, it could be a potential candidate drug against COVID-19.


Subject(s)
Cell Membrane/metabolism , Fenretinide/pharmacology , Membrane Fluidity/drug effects , Oxidoreductases/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Cell Fusion , Cell Membrane/genetics , Gene Knockout Techniques , HEK293 Cells , Humans , Membrane Fluidity/genetics , Oxidoreductases/deficiency , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
9.
Crit Care ; 25(1): 177, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1352667

ABSTRACT

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Pneumonia, Ventilator-Associated/epidemiology , Aged , Europe/epidemiology , Female , Hospital Mortality , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies
10.
J Virol ; 95(17): e0080721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1350004

ABSTRACT

The membrane fusion between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host cells is essential for the initial step of infection; therefore, the host cell membrane components, including sphingolipids, influence the viral infection. We assessed several inhibitors of the enzymes pertaining to sphingolipid metabolism, against SARS-CoV-2 spike protein (S)-mediated cell-cell fusion and viral infection. N-(4-Hydroxyphenyl) retinamide (4-HPR), an inhibitor of dihydroceramide Δ4-desaturase 1 (DES1), suppressed cell-cell fusion and viral infection. The analysis of sphingolipid levels revealed that the inhibition efficiencies of cell-cell fusion and viral infection in 4-HPR-treated cells were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids. We investigated the relationship of DES1 with the inhibition efficiencies of cell-cell fusion. The changes in the sphingolipid profile induced by 4-HPR were mitigated by the supplementation with exogenous cell-permeative ceramide; however, the reduced cell-cell fusion could not be reversed. The efficiency of cell-cell fusion in DES1 knockout (KO) cells was at a level comparable to that in wild-type (WT) cells; however, the ratio of saturated sphinganine-based lipids to the total sphingolipids was higher in DES1 KO cells than in WT cells. 4-HPR reduced cell membrane fluidity without any significant effects on the expression or localization of angiotensin-converting enzyme 2, the SARS-CoV-2 receptor. Therefore, 4-HPR suppresses SARS-CoV-2 S-mediated membrane fusion through a DES1-independent mechanism, and this decrease in membrane fluidity induced by 4-HPR could be the major cause for the inhibition of SARS-CoV-2 infection. IMPORTANCE Sphingolipids could play an important role in SARS-CoV-2 S-mediated membrane fusion with host cells. We studied the cell-cell fusion using SARS-CoV-2 S-expressing cells and sphingolipid-manipulated target cells, with an inhibitor of the sphingolipid metabolism. 4-HPR (also known as fenretinide) is an inhibitor of DES1, and it exhibits antitumor activity and suppresses cell-cell fusion and viral infection. 4-HPR suppresses membrane fusion through a decrease in membrane fluidity, which could possibly be the cause for the inhibition of SARS-CoV-2 infection. There is accumulating clinical data on the safety of 4-HPR. Therefore, it could be a potential candidate drug against COVID-19.


Subject(s)
Cell Membrane/metabolism , Fenretinide/pharmacology , Membrane Fluidity/drug effects , Oxidoreductases/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Cell Fusion , Cell Membrane/genetics , Gene Knockout Techniques , HEK293 Cells , Humans , Membrane Fluidity/genetics , Oxidoreductases/deficiency , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
11.
Phytother Res ; 35(7): 3447-3483, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1323905

ABSTRACT

The pandemic of viral diseases like novel coronavirus (2019-nCoV) prompted the scientific world to examine antiviral bioactive compounds rather than nucleic acid analogous, protease inhibitors, or other toxic synthetic molecules. The emerging viral infections significantly associated with 2019-nCoV have challenged humanity's survival. Further, there is a constant emergence of new resistant viral strains that demand novel antiviral agents with fewer side effects and cell toxicity. Despite significant progress made in immunization and regenerative medicine, numerous viruses still lack prophylactic vaccines and specific antiviral treatments that are so often influenced by the generation of viral escape mutants. Of importance, medicinal herbs offer a wide variety of therapeutic antiviral chemotypes that can inhibit viral replication by preventing viral adsorption, adhering to cell receptors, inhibiting virus penetration in the host cell, and competing for pathways of activation of intracellular signals. The present review will comprehensively summarize the promising antiviral activities of medicinal plants and their bioactive molecules. Furthermore, it will elucidate their mechanism of action and possible implications in the treatment/prevention of viral diseases even when their mechanism of action is not fully understood, which could serve as the base for the future development of novel or complementary antiviral treatments.


Subject(s)
Antiviral Agents , Plants, Medicinal , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Humans , Plants, Medicinal/chemistry , Virus Diseases/drug therapy
12.
Pharmaceuticals (Basel) ; 14(4)2021 Apr 19.
Article in English | MEDLINE | ID: covidwho-1305767

ABSTRACT

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.

13.
Intern Med J ; 52(4): 522-529, 2022 04.
Article in English | MEDLINE | ID: covidwho-1273102

ABSTRACT

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.


Subject(s)
COVID-19 , Thyroiditis, Subacute , Thyrotoxicosis , Adolescent , Adult , Aged , COVID-19/complications , Female , Humans , Male , Middle Aged , Risk Factors , SARS-CoV-2 , Thyroiditis, Subacute/diagnosis , Thyroiditis, Subacute/drug therapy , Thyroiditis, Subacute/epidemiology , Thyrotoxicosis/complications , Thyrotoxicosis/diagnosis , Treatment Outcome , Young Adult
14.
Mol Neurobiol ; 58(9): 4535-4563, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1252224

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a devastating viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The incidence and mortality of COVID-19 patients have been increasing at an alarming rate. The mortality is much higher in older individuals, especially the ones suffering from respiratory distress, cardiac abnormalities, renal diseases, diabetes, and hypertension. Existing evidence demonstrated that SARS-CoV-2 makes its entry into human cells through angiotensin-converting enzyme 2 (ACE-2) followed by the uptake of virions through cathepsin L or transmembrane protease serine 2 (TMPRSS2). SARS-CoV-2-mediated abnormalities in particular cardiovascular and neurological ones and the damaged coagulation systems require extensive research to develop better therapeutic modalities. As SARS-CoV-2 uses its S-protein to enter into the host cells of several organs, the S-protein of the virus is considered as the ideal target to develop a potential vaccine. In this review, we have attempted to highlight the landmark discoveries that lead to the development of various vaccines that are currently under different stages of clinical progression. Besides, a brief account of various drug candidates that are being tested to mitigate the burden of COVID-19 was also covered. Further, in a dedicated section, the impact of SARS-CoV-2 infection on neuronal inflammation and neuronal disorders was discussed. In summary, it is expected that the content covered in this article help to understand the pathophysiology of COVID-19 and the impact on neuronal complications induced by SARS-CoV-2 infection while providing an update on the vaccine development.


Subject(s)
COVID-19 Vaccines , COVID-19/complications , Inflammation/etiology , Neurodevelopmental Disorders/etiology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/physiology , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/adverse effects , Cell Line , Comorbidity , Cytokine Release Syndrome/etiology , Female , Hormesis , Humans , Immunization, Passive , Infectious Disease Transmission, Vertical , Mice , Models, Neurological , Murine hepatitis virus/pathogenicity , Nervous System/virology , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Organ Specificity , Organoids , Pregnancy , Pregnancy Complications, Infectious/virology , Receptors, Virus/physiology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Serine Endopeptidases/physiology , Spike Glycoprotein, Coronavirus/physiology
15.
Emerg Microbes Infect ; 10(1): 1227-1240, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1246665

ABSTRACT

The ongoing pandemic of COVID-19, caused by SARS-CoV-2, has severely impacted the global public health and socio-economic stability, calling for effective vaccines and therapeutics. In this study, we continued our efforts to develop more efficient SARS-CoV-2 fusion inhibitors and achieved significant findings. First, we found that the membrane-proximal external region (MPER) sequence of SARS-CoV-2 spike fusion protein plays a critical role in viral infectivity and can serve as an ideal template for design of fusion-inhibitory peptides. Second, a panel of novel lipopeptides was generated with greatly improved activity in inhibiting SARS-CoV-2 fusion and infection. Third, we showed that the new inhibitors maintained the potent inhibitory activity against emerging SARS-CoV-2 variants, including those with the major mutations of the B.1.1.7 and B.1.351 strains circulating in the United Kingdom and South Africa, respectively. Fourth, the new inhibitors also cross-inhibited other human CoVs, including SARS-CoV, MERS-CoV, HCoV-229E, and HCoV-NL63. Fifth, the structural properties of the new inhibitors were characterized by circular dichroism (CD) spectroscopy and crystallographic approach, which revealed the mechanisms underlying the high binding and inhibition. Combined, our studies provide important information for understanding the mechanism of SARS-CoV-2 fusion and a framework for the development of peptide therapeutics for the treatment of SARS-CoV-2 and other CoVs.


Subject(s)
Drug Design , Lipopeptides/chemical synthesis , Lipopeptides/pharmacology , SARS-CoV-2/drug effects , Virus Attachment/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Fusion , Cell Survival/drug effects , Chlorocebus aethiops , Communicable Diseases, Emerging/virology , HEK293 Cells , Humans , Mutagenesis, Site-Directed , Protein Conformation , Vero Cells
16.
NPJ Syst Biol Appl ; 7(1): 21, 2021 05 24.
Article in English | MEDLINE | ID: covidwho-1241950

ABSTRACT

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.


Subject(s)
COVID-19/genetics , Epigenesis, Genetic/genetics , SARS-CoV-2/genetics , Transcriptome/genetics , COVID-19/virology , Gene Expression Profiling , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/genetics , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Signal Transduction/genetics
17.
Indian J Surg ; 84(2): 386-388, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1237559

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While evaluating nasopharyngeal swabs by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) is diagnostic, thorax computed tomography (CT) findings are also guiding in diagnosis. The association of pneumothorax and pleural effusion is not common in coronavirus disease. We presented the nucleic acid detection by a pleural swab sample in a COVID-19 patient with ground-glass opacity appearance and spontaneous pneumothorax.

18.
Viruses ; 13(5)2021 05 14.
Article in English | MEDLINE | ID: covidwho-1234826

ABSTRACT

Multiple outbreaks of epidemic and pandemic viral diseases have occurred in the last 20 years, including those caused by Ebola virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence or re-emergence of such diseases has revealed the deficiency in our pipeline for the discovery and development of antiviral drugs. One promising solution is the extensive library of antimicrobial peptides (AMPs) produced by all eukaryotic organisms. AMPs are widely known for their activity against bacteria, but many possess additional antifungal, antiparasitic, insecticidal, anticancer, or antiviral activities. AMPs could therefore be suitable as leads for the development of new peptide-based antiviral drugs. Sixty therapeutic peptides had been approved by the end of 2018, with at least another 150 in preclinical or clinical development. Peptides undergoing clinical trials include analogs, mimetics, and natural AMPs. The advantages of AMPs include novel mechanisms of action that hinder the evolution of resistance, low molecular weight, low toxicity toward human cells but high specificity and efficacy, the latter enhanced by the optimization of AMP sequences. In this opinion article, we summarize the evidence supporting the efficacy of antiviral AMPs and discuss their potential to treat emerging viral diseases including COVID-19.


Subject(s)
COVID-19/drug therapy , Pore Forming Cytotoxic Proteins/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Humans , Pandemics , Peptides/metabolism , Peptides/pharmacology , Pore Forming Cytotoxic Proteins/metabolism , SARS-CoV-2/metabolism , Virus Diseases/drug therapy
19.
Sci Rep ; 11(1): 10475, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1233721

ABSTRACT

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 disease. Therapeutic antibodies are being developed that interact with the viral spike proteins to limit viral infection of epithelium. We have applied a method to dramatically improve the performance of anti-SARS-CoV-2 antibodies by enhancing avidity through multimerization using simple engineering to yield tetrameric antibodies. We have re-engineered six anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including three clinical trials antibodies casirivimab, imdevimab and etesevimab. The method yields tetrameric antibodies, termed quads, that retain efficient binding to the SARS-CoV-2 spike protein, show up to two orders of magnitude enhancement in neutralization of pseudovirus infection and retain potent interaction with virus variant of concern spike proteins. The tetramerization method is simple, general and its application is a powerful methodological development for SARS-CoV-2 antibodies that are currently in pre-clinical and clinical investigation.


Subject(s)
SARS-CoV-2/metabolism , Single-Chain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antigen-Antibody Reactions , COVID-19/drug therapy , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , HEK293 Cells , Humans , Neutralization Tests , Protein Domains , Protein Multimerization , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , Recombinant Proteins/therapeutic use , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Single-Chain Antibodies/chemistry , Single-Chain Antibodies/genetics , Single-Chain Antibodies/therapeutic use , Surface Plasmon Resonance , Tumor Suppressor Protein p53/chemistry
20.
Adv Exp Med Biol ; 1318: 169-178, 2021.
Article in English | MEDLINE | ID: covidwho-1222713

ABSTRACT

The present century will undoubtedly be marked with the COVID-19 global health crisis. It is not time yet to talk about the total number of deaths and hospitalizations, as they are enormously growing daily. Understanding the nature of COVID-19-induced pneumonia is vital in order to deal with the associated health complications. Cell stress is an established mechanism known to be associated with infection and cancer. Different proteins crucial for cellular response to stress are reported to be a possible target to stop the infection and to reduce the chemo-resistance in cancer. Heat shock protein (HSP) families of chaperones play an essential role in cells both in normal state and under stress. The upregulation of HSP5A, also termed GRP78 or Bip, is reported in different viral infections. This chapter introduces the current knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the COVID-19 pandemic, and cell stress aimed at defining possible strategies to combat the COVID-19 pandemic.


Subject(s)
COVID-19 , Cell Physiological Phenomena , Neoplasms , Stress, Physiological , Global Health , Humans , Pandemics , SARS-CoV-2
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