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1.
Voprosy Ginekologii, Akusherstva i Perinatologii ; 21(3):28-35, 2022.
Article in Russian | EMBASE | ID: covidwho-2033519

ABSTRACT

Objective. To assess the effectiveness of different preventive measures for novel coronavirus infection in pregnant women. Patients and Methods. This study included 125 pregnant women hospitalized with moderate to severe laboratory-confirmed SARS-CoV-2 infection between September and November 2021 (the fourth pandemic wave), and 175 pregnant women who were not infected with COVID-19 during the same period. All women in these two groups were comparable for gestational age (II–III trimesters, 24–39 weeks), age (20–40 years), social status, parity, body mass index, and had no known COVID-19 risk factors. Results. Our findings revealed that vaccination 3-5 months before pregnancy (OR = 4.12;95% CI 1.28–13.27;χ2 = 0.022), inconsistent use and/or non-timely replacement of face masks (OR = 5.71;95% CI 2.83–11.51) were associated with the increased risk of COVID-19 in the second and third trimesters of gestation. It was showed that systematic (once in the morning at 24–48-hour intervals) intranasal administration of recombinant interferon alpha-2b (IFN-α;Grippferon) as compared with a single application after exposure to COVID-19 reduced the disease incidence rate and there was no evident risk of illness (OR = 0.08;95% CI 0.05–0.14;19.2% vs 74,3%, p < 0.001). This can be explained by the fact that women were mostly infected in unpredictable conditions (e.g., 29.2% of pregnant women were infected from family members, 23.9% had unknown source of exposure). The use of umifenovir, not currently authorised for the medication-assisted prevention of COVID-19 in pregnant women, and rectal administration of IFN-α suppositories did not reduce the disease incidence rate. Rectal use of IFN-α suppositories by pregnant women off-label increased the incidence (32.0 vs 15.4%, p = 0.001) and risk of developing novel coronavirus infection (OR = 2.58;95% CI 1.48–4.50). Conclusion. There is a need to improve awareness among pregnant women about the mandatory and timely vaccination against COVID-19 during pregnancy and the importance of strict adherence to wearing face masks. Increased efforts should be made to monitor and inform pregnant women about the use of only authorised medication-assisted preventive measures of SARS-CoV-2 infection, such as intranasal administration of recombinant IFN α-2b (Grippferon). During the epidemic rise in COVID-19 cases, the systematic intranasal administration of recombinant interferon-based medication Grippferon (once in the morning at 24–48-hour intervals) is recommended for pregnant women.

2.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2032775

ABSTRACT

DEAD-box RNA helicase 21 (DDX21), also known as RHII/Gu, is an ATP-dependent RNA helicase. In addition to playing a vital role in regulating cellular RNA splicing, transcription, and translation, accumulated evidence has suggested that DDX21 is also involved in the regulation of innate immunity. However, whether DDX21 induces or antagonizes type I interferon (IFN-I) production has not been clear and most studies have been performed through ectopic overexpression or RNA interference-mediated knockdown. In this study, we generated DDX21 knockout cell lines and found that knockout of DDX21 enhanced Sendai virus (SeV)-induced IFN-β production and IFN-stimulated gene (ISG) expression, suggesting that DDX21 is a negative regulator of IFN-β. Mechanistically, DDX21 competes with retinoic acid-inducible gene I (RIG-I) for binding to double-stranded RNA (dsRNA), thereby attenuating RIG-I-mediated IFN-β production. We also identified that the 217–784 amino acid region of DDX21 is essential for binding dsRNA and associated with its ability to antagonize IFN production. Taken together, our results clearly demonstrated that DDX21 negatively regulates IFN-β production and functions to maintain immune homeostasis.

3.
Trends Microbiol ; 30(8): 778-792, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1663909

ABSTRACT

The interferon (IFN) response is the major early innate immune response against invading viral pathogens and is even capable of mediating sterilizing antiviral immunity without the support of the adaptive immune system. Cumulative evidence suggests that the gut microbiota can modulate IFN responses, indirectly determining virological outcomes. This review outlines our current knowledge of the interactions between the gut microbiota and IFN responses and dissects the different mechanisms by which the gut microbiota may alter IFN expression to diverse viral infections. This knowledge offers a basis for translating experimental evidence from animal studies into the human context and identifies avenues for leveraging the gut microbiota-IFN-virus axis to improve control of viral infections and performance of viral vaccines.


Subject(s)
Microbiota , Virus Diseases , Animals , Antiviral Agents/therapeutic use , Humans , Immunity, Innate , Interferons/metabolism
4.
HemaSphere ; 6:291-292, 2022.
Article in English | EMBASE | ID: covidwho-2032117

ABSTRACT

Background: The ongoing COVID-19 pandemic has resulted in more than 419 million cases and more than 5.9 million deaths. Preious studies hae indicated inferior responses to SARS-CoV-2 accination across different hematological diseases. Through this prospectie cohort study, we examined the deelopment and durability of anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients with either multiple myeloma (MM) or Chronic Lymphatic B-cell Leukemia (B-CLL) six months after accination and compared to immunocompetent controls. Aims: We aimed to inestigate the durability of immune responses to COVID-19 accination in patients with MM or B-CLL compared to healthy controls, and to identify risk factors for humoral non-response, including type of diagnosis. Methods: We measured anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients (MM: n=78, B-CLL: n=101) and 179 age and sex matched healthy controls up to six months after first accination. Anti- RBD IgG leels and neutralizing capacity of antibodies were measured at first and second dose of BNT162b2 and two and six months after first dose. Humoral response was defined as anti-RBD IgG > 225 AU/mL with a neutralizing index ≥ 25%. Humoral non-response was defined as the absence of a humoral response. T-cell responses were assessed six months after the first dose using an ELISA-based interferon-gamma release assay. A positie T-cell response was defined as IFN-γ release > 200 mIU/mL. Data on diagnoses were obtained through medical records, and data on accination status were obtained from the Danish Vaccination Register. Results: In patients with MM or B-CLL, the geometric mean concentration (GMC) of anti-RBD IgG increased from baseline 1.49 AU/mL (95% CI: 1.21-1.84) to three weeks after the first accine dose 15.10 AU/mL (95% CI: 9.39- 24.29) and after receiing the second dose 1179.60 AU/mL (95% CI: 727.78-1919.85). From two to six months after first accine there was a significant decline in the GMC of anti-RBD IgG to 252.75 AU/mL (95% CI: 159.17-403.43). The mean neutralizing capacity in patients with MM or B-CLL was lower than in controls at all time points after the first accine dose. Six months after first accine dose, 79 of 179 (44.1%) patients with MM or B-CLL had a positie humoral response, while this was the case for 170 of 179 controls (95.0%), p<0.001. Haing MM or B-CLL was significantly associated with risk of humoral non-response. This was most pronounced in B-CLL patients who had an age and sex adjusted risk ratio (RR) of 12.25 (95% CI: 6.42-23.38, p< 0.001) of humoral non-response compared to healthy controls. For MM patients the RR was 4.65 (95% CI: 2.21-9.80, p< 0.001). T-cell response was assessed in a subset of 48 patients with MM (n=28) or B-CLL (n=20) and 26 controls, six months after first accine dose. A total of 21 (43.8%) patients with MM (12/28) or B-CLL (9/20) and 14 (53.8%) controls had a positie T-cell response (p =0.56). Seen of 20 (35.0%) patients with MM or B-CLL who did not deelop a humoral response, deeloped a T-cell response (MM: 3/8, B-CLL: 4/12), while 14 of 28 (50.0%) patients with MM or B-CLL who deeloped a humoral response deeloped a T-cell response (p =0.46, MM: 9/11, B-CLL: 5/8). In healthy controls 14 of 25 (56.0%) people who deeloped a humoral response also deeloped a T-cell response. Summary/Conclusion: Humoral response to BNT162b2 was impaired in patients with MM or B-CLL compared to healthy controls. Both patients with MM and B-CLL were at higher risk of humoral non-response compared to healthy controls.

5.
HemaSphere ; 6:2786-2787, 2022.
Article in English | EMBASE | ID: covidwho-2032115

ABSTRACT

Background: In most individuals, protective humoral and cellular immunity develops after two doses of the BNT162b2 Pfizer vaccine. In patients with lymphoma, humoral response is weaker and almost universally abrogated in patients who received anti-CD20 monoclonal antibodies. Whether cellular immune response is also abrogated is unknown. Aims: To determine whether patients with lymphoma develop specific T-cell mediated cellular response to BNT162b2 Pfizer vaccine. Methods: We included patients with lymphoma above the age of 18 years who received two doses of the BNT162b2 Pfizer vaccine and collected clinical and demographics data. T-cell immune response to the vaccine was analysed in patients' blood samples stimulated by spike antigen and quantified by two methods: (1) Interferon-gamma (IFNg)- release assay (IGRA, EuroImmun, Germany)- IFNg was quantified by ELISA (DuoSet, R and D Systems, Minneapolis, Minnesota, USA) and response above 50 pg/ml was considered positive. (2) Flow cytometry- Quantification of the T cell activation markers, CD134+ CD25+CD4+ T-cells was performed (Act-T4 CellTM kit, Cytognos, Spain), and any response above 0 was considered positive. Humoral response was measured by SARS-CoV-2 IgG II Quant (Abbott©) assay. The positive cut-off was set at 50AU/ml. Blood samples were drawn approximately 4 months after the second vaccination. Results: Sixty-nine lymphoma patients, treated with two vaccine doses, were included in this study. Median age was 66 (range: 30-84) and 39 (57%) were males. Sixty-two patients (90%) had non-Hodgkin lymphoma (NHL) including 18 with DLBCL, 26 with follicular lymphoma and 14 with marginal zone lymphoma. Seven (10%) patients had Hodgkin lymphoma. In this cohort, 70% (n=49) of the patients received anti CD20 MoAb, and 35% of them (n=27) were still on anti CD20 treatment. Thirteen patients received bendamustine-based immunochemotherapy. At the time of assessment (median 4.8 months after the 2nd vaccine) anti-spike antibodies were detected in only 42% (N = 29) of patients. In comparison, there was an increase in specific T cell response by any assay (IGRA and Flow) in 49% of patients (n = 34). The correlation between the IGRA and flow data was 0.7 (pearson correlation, P = 0.01). However, no correlation between humoral (qualitative and quantitative) and T cell response was shown, regardless of the assay applied. Cellular response was not corelated with the time elapsing from last immunochemotherapy. In the anti-CD20 MoAb treated cohort, of which 27 patients were still on active treatment at the time of vaccination, only 2 patients (7%) developed a humoral immune response, while cellular immunity was elicited in 52% (N = 15) patients (ELISA assay). In the Bendamustine treated cohort, with a median time from end of treatment to vaccination of 23 months (1-106 months), humoral but not cellular response correlated positively with the time from treatment completion to vaccination (p=0.04). Summary/Conclusion: The rate of cellular and humoral response to two doses of the BNT162b2 Pfizer vaccine in lymphoma patients was found to be significantly abrogated. In this small cohort, 49% of patients developed a cellular response despite a severely abrogated humoral immunity. These findings suggest that vaccine administration should be considered even early after anti CD20 therapy despite the reduced humoral immunity. These findings should be validated in studies with a higher number of patients.

6.
Signal Transduction and Targeted Therapy ; 7(1), 2022.
Article in English | EMBASE | ID: covidwho-2031821

ABSTRACT

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.

7.
Cell ; 185(19):3588-3588, 2022.
Article in English | Academic Search Complete | ID: covidwho-2027949

ABSTRACT

The current dogma of RNA-mediated innate immunity is that sensing of immunostimulatory RNA ligands is sufficient for the activation of intracellular sensors and induction of interferon (IFN) responses. Here, we report that actin cytoskeleton disturbance primes RIG-I-like receptor (RLR) activation. Actin cytoskeleton rearrangement induced by virus infection or commonly used reagents to intracellularly deliver RNA triggers the relocalization of PPP1R12C, a regulatory subunit of the protein phosphatase-1 (PP1), from filamentous actin to cytoplasmic RLRs. This allows dephosphorylation-mediated RLR priming and, together with the RNA agonist, induces effective RLR downstream signaling. Genetic ablation of PPP1R12C impairs antiviral responses and enhances susceptibility to infection with several RNA viruses including SARS-CoV-2, influenza virus, picornavirus, and vesicular stomatitis virus. Our work identifies actin cytoskeleton disturbance as a priming signal for RLR-mediated innate immunity, which may open avenues for antiviral or adjuvant design. [Display omitted] • Phosphatase-regulatory protein PPP1R12C promotes antiviral defense to RNA virus infection • PPP1R12C mediates RIG-I and MDA5 dephosphorylation and signaling • Actin cytoskeleton disturbance leads to PPP1R12C relocalization and RLR priming • Full RLR activation requires RNA agonist and actin cytoskeleton disturbance Disturbances to the actin cytoskeleton during infection of a cell by an RNA virus drive a specific phosphatase complex to prime RIG-I-like receptors to sense viral RNA, thus promoting effective antiviral responses. [ FROM AUTHOR] Copyright of Cell is the property of Cell Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

8.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-343254

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) caused global pandemics during last three years, the development of new therapeutics is urgently needed. Methods: We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase Ⅰ study to evaluate the safety, tolerability, pharmacokinetics (PK) and cytokine responses after the administration of the recombinant TFF2-IFN proteins. Healthy volunteers were informed, enrolled and randomized into 4 groups with a dose escalation of 0.2, 1, 2, 4 mg/per dose, and then inhaled with the investigation product (IP) or placebo. 32 eligible participants were finally enrolled, 8 were assigned to placebo group and 24 to TFF2-IFN groups with 6 participants per group. Findings: All 32 participants completed the study. 41.7% (10/24) of participants who received recombinant TFF2-IFN protein reported 11 AEs during treatment, and 62.5% (5/8) of participants who received placebo reported 6 AEs. 16 out of total 17 AEs were Grade 1 in severity. Only one Grade 3 AE was occurred in placebo group, and no worse event happened as SAE. The PK were analyzed for the times and concentrations of investigation product in 0.2, 1, 2, 4mg groups in 24 TFF2-IFN recipients, the results showed that TFF2-IFN retains in the lung for at least 6-8 hours, only the highest dose group (4mg/per) has a transient detectable concentration in sera, whereas all other dose groups had a level below the lower limit of quantification (LLOQ). In addition, only IFN-gamma was detectable and none of inflammatory cytokines appeared in sera. Interpretation: In summary, the recombinant TFF2-IFN protein was a well-tolerated and safe therapeutics when administrated through nebulization, featured with prolonged retention in respiratory tract which will be greatly beneficial to combat against respiratory viral infection.

9.
Acta Microbiologica Sinica ; 7(23), 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-2025659

ABSTRACT

Objective: The aim of this study is to screen an ideal adjuvant for an inactivated porcine deltacoronavirus(PDCoV) vaccine to induce mucosal immunity and reduce the side effect of the vaccine. We used different mucosal adjuvants to prepare the inactivated PDCoV vaccines. We then used mouse model to evaluate the humoral, cellular and mucosal immune responses induced by the inactivated vaccines via different immunization routes.

10.
Viruses ; 14(8):1806, 2022.
Article in English | ProQuest Central | ID: covidwho-2024292

ABSTRACT

Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.

11.
Molecules ; 27(16):5080, 2022.
Article in English | ProQuest Central | ID: covidwho-2023932

ABSTRACT

The discovery and the development of safe and efficient therapeutics against arthritogenic alphaviruses (e.g., chikungunya virus) remain a continuous challenge. Alkaloids are structurally diverse and naturally occurring compounds in plants, with a wide range of biological activities including beneficial effects against prominent pathogenic viruses and inflammation. In this short review, we discuss the effects of some alkaloids of three biologically relevant structural classes (isoquinolines, indoles and quinolizidines). Based on various experimental models (viral infections and chronic diseases), we highlight the immunomodulatory effects of these alkaloids. The data established the capacity of these alkaloids to interfere in host antiviral and inflammatory responses through key components (antiviral interferon response, ROS production, inflammatory signaling pathways and pro- and anti-inflammatory cytokines production) also involved in alphavirus infection and resulting inflammation. Thus, these data may provide a convincing perspective of research for the use of alkaloids as immunomodulators against arthritogenic alphavirus infection and induced inflammation.

12.
International Journal of Molecular Sciences ; 23(17):9914, 2022.
Article in English | ProQuest Central | ID: covidwho-2023752

ABSTRACT

Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections. Furthermore, in most cases, asthmatic patients tend to produce lower levels of antiviral cytokines than healthy subjects, such as interferons produced from immune effector cells and airway epithelial cells. The epithelial inflammasome appears to contribute to asthma exacerbation through overactivation, leading to self-damage, despite its naturally protective role against infectious pathogens. Given the mixed and complex immune responses in viral-infection-induced asthma exacerbation, this review examines the diverse roles of airway epithelial immunity and related potential therapeutic targets and discusses the mechanisms underlying the heterogeneous manifestations of asthma exacerbations.

13.
International Journal of Molecular Sciences ; 23(17):9653, 2022.
Article in English | ProQuest Central | ID: covidwho-2023745

ABSTRACT

Discovery of the microbiota-gut–brain axis has led to proposed microbe-based therapeutic strategies in mental health, including the use of mood-altering bacterial species, termed psychobiotics. However, we still have limited understanding of the key signaling pathways engaged by specific organisms in modulating brain function, and evidence suggests that bacteria with broadly similar neuroactive and immunomodulatory actions can drive different behavioral outcomes. We sought to identify pathways distinguishing two psychoactive bacterial strains that seemingly engage similar gut–brain signaling pathways but have distinct effects on behaviour. We used RNAseq to identify mRNAs differentially expressed in the blood and hippocampus of mice following Lacticaseibacillus rhamnosus JB-1, and Limosilactobacillus reuteri 6475 treatment and performed Gene Set Enrichment Analysis (GSEA) to identify enrichment in pathway activity. L. rhamnosus, but not L. reuteri treatment altered several pathways in the blood and hippocampus, and the rhamnosus could be clearly distinguished based on mRNA profile. In particular, L. rhamnosus treatment modulated the activity of interferon signaling, JAK/STAT, and TNF-alpha via NF-KB pathways. Our results highlight that psychobiotics can induce complex changes in host gene expression, andin understanding these changes, we may help fine-tune selection of psychobiotics for treating mood disorders.

14.
Frontiers in Immunology ; 13, 2022.
Article in English | Scopus | ID: covidwho-2022745

ABSTRACT

Influenza vaccines remain the most effective tools to prevent flu and its complications. Trivalent or quadrivalent inactivated influenza vaccines primarily elicit antibodies towards haemagglutinin and neuraminidase. These vaccines fail to induce high protective efficacy, in particular in older adults and immunocompromised individuals and require annual updates to keep up with evolving influenza strains (antigenic drift). Vaccine efficacy declines when there is a mismatch between its content and circulating strains. Current correlates of protection are merely based on serological parameters determined by haemagglutination inhibition or single radial haemolysis assays. However, there is ample evidence showing that these serological correlates of protection can both over- or underestimate the protective efficacy of influenza vaccines. Next-generation universal influenza vaccines that induce cross-reactive cellular immune responses (CD4+ and/or CD8+ T-cell responses) against conserved epitopes may overcome some of the shortcomings of the current inactivated vaccines by eliciting broader protection that lasts for several influenza seasons and potentially enhances pandemic preparedness. Assessment of cellular immune responses in clinical trials that evaluate the immunogenicity of these new generation vaccines is thus of utmost importance. Moreover, studies are needed to examine whether these cross-reactive cellular immune responses can be considered as new or complementary correlates of protection in the evaluation of traditional and next-generation influenza vaccines. An overview of the assays that can be applied to measure cell-mediated immune responses to influenza with their strengths and weaknesses is provided here. Copyright © 2022 Janssens, Joye, Waerlop, Clement, Leroux-Roels and Leroux-Roels.

15.
European Journal of Dermatology ; 32(3):377-383, 2022.
Article in English | MEDLINE | ID: covidwho-2022182

ABSTRACT

Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection. Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to focus on IFN-I expression in patients with chilblains. Materials & Methods: A monocentric cohort of 43 patients presenting with CL from April 2020 to May 2021 were included. During this period, all CL were, a priori, considered to be SARS-CoV-2-related. RT-qPCR on nasopharyngeal swabs and measurements of anti-SARS-CoV-2 antibodies were performed. Anti-SARS-CoV-2 immunostainings as well as SARS-CoV-2 RT-qPCR were performed on biopsy specimens of CL and controls. Expression of MX1 and IRF7 was analysed on patients' biopsy specimens and/or PBMC and compared with controls and/or chilblains observed before the pandemic. Serum IFN-alpha was also measured. Results: RT-qPCR was negative in all patients and serological tests were positive in 11 patients. Immunostaining targeting viral proteins confirmed the lack of specificity. SARS-CoV-2 RNA remained undetected in all CL specimens. MX1 immunostaining was positive in CL and in pre-pandemic chilblains compared to controls. MX1 and IRF7 expression was significantly increased in CL specimens but not in PBMC. Serum IFN-alpha was undetected in CL patients. Conclusion: CL observed during the pandemic do not appear to be directly related to SARS-CoV-2 infection, either based on viral cytopathogenicity or high IFN-I response induced by the virus.

16.
Clin Infect Dis ; 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-2017796

ABSTRACT

BACKGROUND: We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after SARS-CoV-2 infection or vaccination. METHODS: This prospective study included COVID-19 patients with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of RT-PCR or vaccination was considered as reference standard. RESULTS: Two hundred and thirty nine individuals were included (152 convalescent, 54 vaccinated and 33 uninfected unvaccinated). Overall sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (95% CI) of the IGRA were 81.1% (74.9%-86%), 90.9% (74.5%-97.6%), 98.2% (94.5%-99.5%), and 43.5% (31.8%-55.9%), respectively. All vaccinated SARS-CoV-2-naïve subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3-month and the worst in those with mild disease at 12-month. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). CONCLUSION: The IGRA assessed was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.

17.
J Infect Dis ; 2022.
Article in English | PubMed | ID: covidwho-2017962

ABSTRACT

Interferon (IFN)-specific autoantibodies have been implicated in severe COVID-19 and have been proposed as a potential driver of the persistent symptoms characterizing Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC). We report than only two of 215 SARS-CoV-2 convalescent participants tested over 394 timepoints, including 121 people experiencing Long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to Long COVID symptoms in the post-acute phase of the infection.

18.
Clin Infect Dis ; 2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-2017815

ABSTRACT

While SARS-CoV-2 vaccines prevent severe disease effectively, post-vaccination 'breakthrough' COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type1 interferon in the presumptive index case.

19.
International Journal of Infectious Diseases ; 122:537-542, 2022.
Article in English | Web of Science | ID: covidwho-2015429

ABSTRACT

Objectives: Interferon- gamma release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. Methods: We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. Results: A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon- gamma concentrations over the Nil ( P = 0.005) and increased Mitogen-Nil ( P < 0.001) values after vaccination. For TB2-Nil value, a similar trend ( P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than ;+/- 0.10;IU/ml over the TB1-Nil and TB2-Nil values in > 90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRApositive cases. Conclusion: COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

20.
International Journal of Pharmaceutical Sciences Review and Research ; 75(2):62-69, 2022.
Article in English | EMBASE | ID: covidwho-2010617

ABSTRACT

Diabetes is a chronic metabolic disorder emerging as a global burden. Diabetes serves as a risk factor for many complications inclusive of COVID-19. The SARS – 2 pathogens have led to Coronavirus disease. Coronaviruses are enveloped viruses with a single-stranded, positive-sense RNA genome recognized to cause respiratory infections in human beings. Diabetes patients being affected by coronavirus become more critical due to worsening hyperglycemia induces aggravation, endothelial dysfunction, and occlusion of blood vessels through the era of oxidative stress riding the down-regulation of glucose metabolism and hyperglycemia. Increased glucose level causes inflammation and tissue damage serves as a supportive factor for higher tissue damage in COVID patients. Sufferers with extreme COVID-19 have an exceptionally impaired interferon type 1 response with low IFN alpha activity in the blood, indicating excessive blood viral load, and an impaired inflammatory response. This can be alleviated by regular screening and appropriate therapy as like as metformin, camostat mesylate, chloroquine, and adjunctive therapy. Metformin is the desired preliminary drug to deal with T2DM. Camostat mesylate drug accelerated glycemia and insulin resistance and reduced fat buildup in mammalian models. Adjunctive treatment can be used to obviate the evolution of COVID-19.

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