Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Minerva Endocrinol (Torino) ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1737520

ABSTRACT

BACKGROUND: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. METHODS: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. RESULTS: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac Troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. CONCLUSIONS: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19.

2.
Viruses ; 14(3)2022 03 05.
Article in English | MEDLINE | ID: covidwho-1732241

ABSTRACT

Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave (n = 35) and second wave (n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.


Subject(s)
COVID-19 , Humans , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307685

ABSTRACT

Importance: Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seems to be lower in children compared to that in adults. Defining the pathophysiological mechanisms of such disease patterns maybe relevant for development of effective public health strategies. It has been hypothesised that the lower severity of SARS-CoV-2 infection in children could be due to the differential expression of angiotensin-converting enzyme 2 (ACE2), which serves as a virus receptor.Objective: To evaluate the expression of ACE2, ACE1, and TMPRSS2 genes at the level of the two most relevant entry sites for SARS-CoV-2, the upper respiratory tract and small intestine, in healthy children and adult subjects.Design, Setting, and Participants: This prospective study included healthy individuals of both sexes, aged 1-10 years in the paediatric population (n=30) and 20-80 years in the adult population (n=30). The participants were consecutively evaluated at two tertiary centres for paediatrics, gastroenterology, and otolaryngology.Main Measures: Expression of ACE2, ACE1, and TMPRSS2 genes in samples collected from the upper respiratory tract and small intestine.Results: We found no difference in ACE2, ACE1, and TMPRSS2 expression in the nasal epithelium between children and adult subjects. ACE2 expression was more abundant in the small intestine of children compared to that in adults. ACE1 expression was higher in the small intestine of adults compared to that in children. Intestinal TMPRSS2 expression was similar in the two study populations.Conclusions and Relevance: The general lower severity of SARS-CoV-2 infection in children does not seem to be related to a lower expression of ACE2 and/or TMPRSS2 in the respiratory tract or in the gastrointestinal tract. Other co-factors may confer protection against SARS-CoV-2 in children. The exploration of such factors is of pivotal importance for development of innovative protective strategies against SARS-CoV-2.Funding Statement: This work was supported in part by a grant of Regione Campania POR FESR 2014/2020, Task Force Covid-19 DGR 140 – 17 March 2020.Declaration of Interests: The authors have no other conflict of interests that are directly relevant to the content of this manuscript, which remains their sole responsibility.Ethics Approval Statement: The study was approved by the Ethics Committee of the University Federico II of Naples, Italy. Written informed consent was obtained from the adult participants and from the parents/tutors of minors.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320873

ABSTRACT

COVID-19 is a complex disease and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated. The evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, while the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. Lastly, conflicting data were found regarding to the use of convalescent plasma and vitamin D. According to data shared by the WHO, many vaccines are under phase 3 clinical trials and some of them already received the marketing approval in EU countries and in the US. In conclusion, drugs repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, the analysis of efficacy and safety data of drugs and vaccines used in real life context is strongly needed.

5.
Mediastinum (Hong Kong, China) ; 5, 2021.
Article in English | EuropePMC | ID: covidwho-1668568

ABSTRACT

Background Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system with humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients. The aim of our study is evaluating immunization in TET patients, who received both doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods Starting from 14 April 2021, we enrolled 50 TET patients (pts), who received COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody serological levels were analysed by chemiluminescent immunoassay (CLIA) at different time-points: T0 (before the first vaccine dose), T1 (1 week after second dose), T2 (4 weeks after second dose), and late monitoring T3, T4, T5, T6 (at 3, 6, 9, 12 months after second dose, respectively). Preliminary data relative to12 pts, collected at T0, T1 and T2, were available for this report. Local ethical committee approved this study and all enrolled patients signed informed consent. Results Among the 12 patients, 8 were female and 4 males;9 pts had thymoma and 3 thymic carcinomas;myasthenia gravis (autoimmunity) was diagnosed in one patient, and 4 patients suffered from Good Syndrome (immunodeficiency). None had COVID-19 infection prior to immunization. All 12 pts had received both vaccine doses by the time of this analysis. At baseline, all pts were negative for the serological antibody titers (method range, 3.80–400 AU/mL, positivity for titer >25);at T1, 11 pts (92%) were negative;at T2, 10 pts (84%) remained negative. Interestingly, the only 2 pts with positive titers at T2 were both in remission of disease. Conclusions Our preliminary data showed that the majority of TET patients enrolled in this study had no seroconversion after 4 weeks from the second dose of COVID 19 vaccine. Despite preliminary, our data might have important implications for the immunization of TET patients.

6.
Sci Rep ; 12(1): 1212, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1649849

ABSTRACT

The molecular basis of the wide clinical heterogeneity of Coronavirus disease 2019 (COVID-19) is still unknown. Matrix metalloproteinases (MMPs) may have a role in the lung damage and regeneration that occur in severe patients. We studied serum MMP3 and MMP9 as potential biomarkers of COVID-19 severity, in 108 hospitalized patients with different World Health Organization (WHO) severity stage and in 48 controls. At hospital admission, serum MMP3 was increased in COVID-19 patients with a significant trend along the progression of the WHO stage, while serum levels of MMP9 were significantly increased in COVID-19 patients with no correlation with disease severity. At 1 week from hospitalization, MMP3 was reduced, suggesting an early pathogenic role of the protein in lung inflammation, while MMP9 levels were further increased, indicating a late role of the protein in the inflammatory process, specifically during the repairing phase. Furthermore, serum MMP9 was positively correlated with serum interleukin-6, myeloperoxidase, and circulating neutrophils and monocytes number. In conclusion, serum MMP3 may help to early predict the severity of COVID-19 and both proteins, MMP3 and MMP9, may contribute to define severe COVID-19 patients that may benefit from a targeted therapy on MMPs.


Subject(s)
COVID-19/blood , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 9/blood , Patient Acuity , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged
10.
J Transl Med ; 19(1): 403, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438276

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic had a 1st wave in Europe from March to May 2020 and a 2nd wave since September 2020. We previously studied 35 hospitalized COVID-19 patients of the 1st wave demonstrating a cytokine storm and the exhaustion of most lymphocyte subpopulations. Herein, we describe the results obtained from COVID-19 patients of the 2nd wave. METHODS: We analyzed interleukin (IL)-6 by human-specific enzyme-linked immunosorbent assay and a large set of lymphocyte subpopulations by flow cytometry in 274 COVID-19 patients hospitalized from September 2020 to May 2021. RESULTS: Patients of 2nd wave compared with those of 1st wave showed lower serum IL-6 levels and a higher number of B and most T lymphocyte subpopulations in advanced stages, in relation with the age and the gender. On the other hand, we observed in 2nd wave patients: (i) a reduction of most lymphocyte subpopulations at mild and moderate stages; (ii) a reduction of natural killer cells and T regulatory cells together with a higher number of activated T helper (TH) 17 lymphocytes in all stages, which were mainly related to steroid and azithromycin therapies before hospitalization. CONCLUSIONS: COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate specific IL/lymphocyte inhibition or activation in COVID-19 patients.


Subject(s)
COVID-19 , Humans , Killer Cells, Natural , Lymphocyte Count , Pandemics , SARS-CoV-2
11.
Biomolecules ; 11(9)2021 09 16.
Article in English | MEDLINE | ID: covidwho-1408458

ABSTRACT

Systemic vascular damage with micro/macro-thrombosis is a typical feature of severe COVID-19. However, the pathogenesis of this damage and its predictive biomarkers remain poorly defined. For this reason, in this study, serum monocyte chemotactic protein (MCP)-2 and P- and E-selectin levels were analyzed in 204 patients with COVID-19. Serum MCP-2 and P-selectin were significantly higher in hospitalized patients compared with asymptomatic patients. Furthermore, MCP-2 increased with the WHO stage in hospitalized patients. After 1 week of hospitalization, MCP-2 levels were significantly reduced, while P-selectin increased in patients in WHO stage 3 and decreased in patients in WHO stages 5-7. Serum E-selectin was not significantly different between asymptomatic and hospitalized patients. The lower MCP-2 levels after 1 week suggest that endothelial damage triggered by monocytes occurs early in COVID-19 disease progression. MCP-2 may also predict COVID-19 severity. The increase in P-selectin levels, which further increased in mild patients and reduced in severe patients after 1 week of hospitalization, suggests that the inactive form of the protein produced by the cleavage of the active protein from the platelet membrane is present. This may be used to identify a subset of patients that would benefit from targeted therapies. The unchanged levels of E-selectin in these patients suggest that endothelial damage is less relevant.


Subject(s)
COVID-19 , Chemokine CCL8/blood , E-Selectin/blood , Endothelium, Vascular , P-Selectin/blood , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , COVID-19/pathology , Endothelium, Vascular/injuries , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Humans , Male , Middle Aged , Monocytes/metabolism , Monocytes/pathology
12.
Int J Mol Sci ; 22(17)2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1390657

ABSTRACT

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.


Subject(s)
Biomarkers/blood , Carbon/metabolism , Liver/metabolism , Metabolome , Nitrogen/metabolism , Amino Acids/metabolism , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cytokines/blood , Discriminant Analysis , Humans , Least-Squares Analysis , Metabolic Networks and Pathways/genetics , Metabolomics/methods , SARS-CoV-2/isolation & purification , Severity of Illness Index
13.
Viruses ; 13(9)2021 08 29.
Article in English | MEDLINE | ID: covidwho-1374540

ABSTRACT

A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , COVID-19/blood , COVID-19/virology , SARS-CoV-2 , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/etiology , COVID-19/diagnosis , COVID-19/immunology , Disease Susceptibility , Female , Humans , Immunoassay , Male , Middle Aged , Pilot Projects , Symptom Assessment
14.
Front Pediatr ; 9: 697390, 2021.
Article in English | MEDLINE | ID: covidwho-1357534

ABSTRACT

Background: Clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seem to differ in children compared to that in adults. It has been hypothesized that the lower clinical severity in children could be influenced by differential expression of the main host functional receptor to SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2), but data are still conflicting. To explore the origin of age-dependent clinical features of coronavirus disease 2019 (COVID-19), we comparatively evaluated the expression in children and adult subjects of the most relevant mediators of the SARS-CoV-2 infection: ACE2, angiotensin-converting enzyme 1 (ACE1), transmembrane serine protease-2 (TMPRSS2), and neuropilin-1 (NRP1), at upper respiratory tract and small intestine level. Methods: The expression of ACE2, ACE1, TMPRSS2, and NRP1 in nasal epithelium and in small intestine epithelium was investigated by quantitative real-time PCR analysis. Results: We found no differences in ACE2, ACE1, and TMPRSS2 expression in the nasal epithelium comparing children and adult subjects. In contrast, nasal epithelium NRP1 expression was lower in children compared to that in adults. Intestinal ACE2 expression was higher in children compared to that in adults, whereas intestinal ACE1 expression was higher in adults. Intestinal TMPRSS2 and NRP1 expression was similar comparing children and adult subjects. Conclusions: The lower severity of SARS-CoV-2 infection observed in children may be due to a different expression of nasal NRP1, that promotes the virus interaction with ACE2. However, the common findings of intestinal symptoms in children could be due to a higher expression of ACE2 at this level. The insights from these data will be useful in determining the treatment policies and preventive measures for COVID-19.

15.
Front Oncol ; 11: 705948, 2021.
Article in English | MEDLINE | ID: covidwho-1346413

ABSTRACT

BACKGROUND: We report the case of a woman with non-Hodgkin lymphoma who remained positive on the molecular assay for SARS-CoV-2 for six months: she has never experienced a severe form of COVID-19 although in absence of seroconversion. METHODS: The whole SARS-CoV-2 genome analysis was performed by the CleanPlex SARS-CoV-2 Research and Surveillance NGS Panel (PARAGON GENOMICS, Hayward, USA). RESULTS: We found twenty-two mutations in SARS-CoV-2 genome and a novel deleterious ORF3a frameshift c.766_769del corresponding to a unique and novel lineage. The region affected by this frameshift variant is reported as being important in determining SARS-CoV-2 immunogenicity. Patient's immunophenotype showed the absence of B lymphocytes and significantly reduced T-cell count. Only after the treatment with hyperimmune plasma she finally became negative on the swab. CONCLUSIONS: Our findings could be helpful in the management of patients with immunodeficiency, particularly when novel variants, potentially altering the virus immune response, are present.

16.
Sci Signal ; 14(690)2021 07 06.
Article in English | MEDLINE | ID: covidwho-1299215

ABSTRACT

Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO4 3-) units linked together by multiple high-energy phosphoanhydride bonds. In addition to being a source of energy, polyPs have cytoprotective and antiviral activities. Here, we investigated the antiviral activities of long-chain polyPs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In molecular docking analyses, polyPs interacted with several conserved amino acid residues in angiotensin-converting enzyme 2 (ACE2), the host receptor that facilitates virus entry, and in viral RNA-dependent RNA polymerase (RdRp). ELISA and limited proteolysis assays using nano- LC-MS/MS mapped polyP120 binding to ACE2, and site-directed mutagenesis confirmed interactions between ACE2 and SARS-CoV-2 RdRp and identified the specific amino acid residues involved. PolyP120 enhanced the proteasomal degradation of both ACE2 and RdRp, thus impairing replication of the British B.1.1.7 SARS-CoV-2 variant. We thus tested polyPs for functional interactions with the virus in SARS-CoV-2-infected Vero E6 and Caco2 cells and in primary human nasal epithelial cells. Delivery of a nebulized form of polyP120 reduced the amounts of viral positive-sense genomic and subgenomic RNAs, of RNA transcripts encoding proinflammatory cytokines, and of viral structural proteins, thereby presenting SARS-CoV-2 infection in cells in vitro.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Polyphosphates/pharmacology , SARS-CoV-2/drug effects , Administration, Inhalation , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , COVID-19/metabolism , COVID-19/virology , Caco-2 Cells , Chlorocebus aethiops , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cytokines/metabolism , HEK293 Cells , Host Microbial Interactions/drug effects , Host Microbial Interactions/genetics , Host Microbial Interactions/physiology , Humans , In Vitro Techniques , Models, Biological , Molecular Docking Simulation , Nebulizers and Vaporizers , Polyphosphates/administration & dosage , Polyphosphates/chemistry , Proteasome Endopeptidase Complex/metabolism , Protein Interaction Domains and Motifs , Proteolysis/drug effects , RNA, Viral/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Sequence Homology, Amino Acid , Signal Transduction/drug effects , Vero Cells , Virus Replication/drug effects
17.
Front Public Health ; 9: 664108, 2021.
Article in English | MEDLINE | ID: covidwho-1295722

ABSTRACT

COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality. Accordingly, we found that NLR significantly increased in parallel with the WHO severity stage in COVID-19 patients during the Ist wave (March-May 2020; n = 49), due to the significant reduction of lymphocyte and the significant increase of neutrophil in severe COVID-19 patients. While, we did not observe significant differences of NLR between the WHO severity stage among COVID-19 patients of the IInd wave (September 2020-April 2021; n = 242). In these patients, the number of lymphocytes and neutrophils did not change significantly between patients of different severity subgroups. This difference likely depends on the steroids therapy that the patients of the IInd wave performed before hospitalization while most patients of the Ist wave were hospitalized soon after diagnosis. This is also confirmed by serum interleukin (IL)-6 and myeloperoxidase (MPO) that gradually increased with the disease stage in patients of the Ist wave, while such biomarkers (whose production is inhibited by steroids) did not show differences among patients of the IInd wave in different stages. Thus, the NLR could be tested at diagnosis in naïve patients before starting therapies.


Subject(s)
COVID-19 , Neutrophils , Humans , Lymphocyte Count , Lymphocytes , Prognosis , Retrospective Studies , SARS-CoV-2
18.
Biomedicines ; 9(6)2021 May 27.
Article in English | MEDLINE | ID: covidwho-1256425

ABSTRACT

Since the beginning of 2020, the new pandemic caused by SARS-CoV-2 and named coronavirus disease 19 (COVID 19) has changed our socio-economic life. In just a few months, SARS-CoV-2 was able to spread worldwide at an unprecedented speed, causing hundreds of thousands of deaths, especially among the weakest part of the population. Indeed, especially at the beginning of this pandemic, many reports highlighted how people, suffering from other pathologies, such as hypertension, cardiovascular diseases, and diabetes, are more at risk of severe outcomes if infected. Although this pandemic has put the entire academic world to the test, it has also been a year of intense research and many important contributions have advanced our understanding of SARS-CoV-2 origin, its molecular structure and its mechanism of infection. Unfortunately, despite this great effort, we are still a long way from fully understanding how SARS-CoV-2 dysregulates organismal physiology and whether the current vaccines will be able to protect us from possible future pandemics. Here, we discuss the knowledge we have gained during this year and which questions future research should address.

19.
Br J Pharmacol ; 179(10): 2128-2148, 2022 May.
Article in English | MEDLINE | ID: covidwho-1219951

ABSTRACT

COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.


Subject(s)
COVID-19 , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/therapy , Drug Repositioning , Humans , Immunization, Passive , SARS-CoV-2
20.
Front Cell Infect Microbiol ; 11: 625581, 2021.
Article in English | MEDLINE | ID: covidwho-1116652

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 (COVID-19). This virus is highly transmissible among individuals through both droplets and aerosol leading to determine severe pneumonia. Among the various factors that can influence both the onset of disease and the severity of its complications, the microbiome composition has also been investigated. Recent evidence showed the possible relationship between gut, lung, nasopharyngeal, or oral microbiome and COVID-19, but very little is known about it. Therefore, we aimed to verify the relationships between nasopharyngeal microbiome and the development of either COVID-19 or the severity of symptoms. To this purpose, we analyzed, by next generation sequencing, the hypervariable V1-V2-V3 regions of the bacterial 16S rRNA in nasopharyngeal swabs from SARS-CoV-2 infected patients (n=18) and control (CO) individuals (n=12) using Microbiota solution A (Arrow Diagnostics). We found a significant lower abundance of Proteobacteria and Fusobacteria in COVID-19 patients in respect to CO (p=0.003 and p<0.0001, respectively) from the phylum up to the genus (p<0.001). The Fusobacterium periodonticum (FP) resulted as the most significantly reduced species in COVID-19 patients respect to CO. FP is reported as being able to perform the surface sialylation. Noteworthy, some sialic acids residues on the cell surface could work as additional S protein of SARS-CoV-2 receptors. Consequently, SARS-CoV-2 could use sialic acids as receptors to bind to the epithelium of the respiratory tract, promoting its clustering and the disease development. We can therefore speculate that the significant reduction of FP in COVID-19 patients could be directly or indirectly linked to the modulation of sialic acid metabolism. Finally, viral or environmental factors capable of interfering with sialic metabolism could determine a fall in the individual protection from SARS-CoV-2. Further studies are necessary to clarify the precise role of FP in COVID-19.


Subject(s)
COVID-19/epidemiology , Fusobacterium Infections/microbiology , Fusobacterium/growth & development , Microbiota , N-Acetylneuraminic Acid/metabolism , Pandemics , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , COVID-19/virology , Female , Fusobacterium/genetics , Humans , Male , Middle Aged , Mouth/microbiology , Nasopharynx/microbiology
SELECTION OF CITATIONS
SEARCH DETAIL