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1.
In Silico Pharmacol ; 10(1): 12, 2022.
Article | MEDLINE | ID: covidwho-1959193

ABSTRACT

Despite the availability of COVID-19 vaccines, additional more potent vaccines are still required against the emerging variations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the present investigation, we have identified a promising vaccine candidate against the Omicron (B.1.1.529) using immunoinformatics approaches. Various available tools like, the Immune Epitope Database server resource, and NetCTL-1.2, have been used for the identification of the promising T-cell and B-cell epitopes. The molecular docking was performed to check the interaction of TLR-3 receptors and validated 3D model of vaccine candidate. The codon optimization was done followed by cloning using SnapGene. Finally, In-silico immune simulation profile was also checked. The identified T-cell and B-cell epitopes have been selected based on their antigenicity (VaxiJen v2.0) and, allergenicity (AllerTOP v2.0). The identified epitopes with antigenic and non-allergenic properties were fused with the specific peptide linkers. In addition, the 3D model was constructed by the PHYRE2 server and validated using ProSA-web. The validated 3D model was further docked with the Toll-like receptor 3 (TLR3) and showed good interaction with the amino acids which indicate a promising vaccine candidate against the Omicron variant of SARS-CoV-2. Finally, the codon optimization, In-silico cloning and immune simulation profile was found to be satisfactory. Overall, the designed vaccine candidate has a potential against variant of SARS-Cov-2. However, further experimental studies are required to confirm.

2.
British Journal of Dermatology ; 186(6):e252, 2022.
Article in English | EMBASE | ID: covidwho-1956690

ABSTRACT

A 44-year-old man of Pakistani origin presented to emergency 6 days following his first dose of the AstraZeneca (AZ) SARSCoV- 2 vaccine. He developed flu-like symptoms followed by erythematous pruritic rash. Physical examination showed a maculopapular rash associated with purpura and targetoid lesions affecting his distal extremities, trunk and mucous membranes. He also had crusting and ulceration of his oral and genital mucosal areas. He had no other significant past medical history. A biopsy was taken from his right arm and sent for urgent histology and direct immunofluorescence. Histology revealed parakeratotic scale with interface dermatitis comprising basal layer vacuolation and lymphocyte exocytosis. The epidermis showed prominent dyskeratotic keratinocytes scattered throughout the epidermis. The papillary dermis showed a mild perivascular lymphocytic infiltrate including eosinophils and melanophages. Other investigations showed leucocytosis (12 × 109 L-1), high eosinophils (0.9 × 109 L-1), raised liver enzymes with alkaline phosphatase 159 U L-1 and alanine aminotransferase 172 U L-1. A full infection screen, including herpes simplex virus, SARS-CoV-2 and atypical viral infection, was negative. Immunology was also reported as negative. Based on the findings, a diagnosis of erythema multiforme (EM) secondary to AZ vaccine was made. He was treated with topical steroids and emollients, leading to resolution of his skin and mucosal areas in 4-6 weeks. Recently, there have been a few reported cases of EM in patients with COVID-19 (Jimenez-Cauhe J, Ortega-Quijano D, Carretero- Barrio I et al. Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings. Clin Exp Dermatol 2020;45: 892-5) and two patients who have had the Pfizer-BioNTech vaccine [Kim M, Kim J, Kim M et al. Generalized erythema multiforme-like skin rash following the first dose of COVID-19 vaccine (Pfizer-BioNTech). J Eur Acad Dermatol Venereol 2021], but the information is limited. Our case emphasizes the need for further studies into the cutaneous adverse effects related to COVID-19vaccines.

3.
Pakistan Paediatric Journal ; 46(2):229-232, 2022.
Article in English | EMBASE | ID: covidwho-1955740

ABSTRACT

Staphylococcal aureus infection in children is a major public health problem globally. It causes a varied spectrum of clinical disease including bacteremia, endocarditis, skin and soft tissue infection, pleuro-pulmaonry and osteo-articular infection. Deep vein thrombosis (DVT) is a known complication of staphylococcal infection. We report a case series which included, 10-year old boy developed DVT, septic pulmonary emboli and Methicillin-resistant Staphylococcal aureus (MRSA) bacteremia following a furuculosis and 13 year old girl with thrombosis of internal and external jugular vein, cavernous sinus with pulmonary emboli and MRA bacteremia. Both patients are previously healthy showed complete recovery after aggressive appropriate antibiotics, anticoagulants and supportive care. The high index of suspicion of DVT in MRSA infection is needed, prompt diagnosis and aggressive appropriate therapies improve the outcomes and minimize the complications.

4.
Immunol Res ; 70(4): 419-431, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1956007

ABSTRACT

Ehlers-Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.


Subject(s)
Arthritis, Rheumatoid , Ehlers-Danlos Syndrome , Joint Instability , Muscular Diseases , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/epidemiology , Ehlers-Danlos Syndrome/genetics , Humans , Joint Instability/diagnosis , Mast Cells , Syndrome
5.
Clin Transl Immunology ; 11(7): e1405, 2022.
Article in English | MEDLINE | ID: covidwho-1955899

ABSTRACT

Symptoms and outcomes for paediatric COVID-19 differ vastly from those for adults, with much lower morbidity and mortality. Immunopathogenesis drives severe outcomes in adults, and it is likely that age-related differences in both the innate and specific immune responses underlie much of the variation. Understanding the protective features of the paediatric immune system may be crucial to better elucidate disease severity in adult COVID-19 and may pave the way for novel therapeutic approaches. However, as well as uncommon cases of severe paediatric acute COVID-19, there have been children who have presented with delayed multisystem inflammation, including cardiac, gastrointestinal, skin, mucosa and central nervous system involvement. The occurrence of coronary artery aneurysms has drawn comparisons with Kawasaki Disease, but similarities with the inflammatory phase of adult acute COVID-19 have also been drawn. In this review, we summarise findings from studies investigating pre-existing immunity, cytokine profiles, innate, B-cell, antibody, T-cell and vaccine responses in children with acute COVID-19 and multisystem inflammation, compared with COVID-19 adults and controls. We further consider the relevance to therapeutics in the context of limited evidence in children and highlight key questions to be answered about the immune response of children to SARS-CoV-2.

6.
Proceedings of the Shevchenko Scientific Society. Medical Sciences ; 66(1):22-35, 2022.
Article in English, Ukrainian | Scopus | ID: covidwho-1955381

ABSTRACT

Traditionally, before the beginning of the Christmas season in Lviv, the Department of Clinical Immunology and Allergology of Danylo Halytsky Lviv National Medical Uni- versity, headed by the Honorary Doctor of Ukraine, Doctor of Medical Science, Pro- fessor Valentyna Chopyak, organizes inter- national conferences on clinical immunolo- gy, allergology and related disciplines. This year, which is the tenth anniversary of this tradition, the Conference, held on December 9-10, was dedicated to the most urgent issue of the year “COVID-19, LONG-COVID-19, POST-COVID-19: THEIR MULTIPLICITY AND IMMUNE DISORDERS”. The conference was organized jointly with the Ministry of Health of Ukraine, NAS of Ukraine and NAMS of Ukraine, Danylo Halytsky Lviv National Medical University, Department of Health of Lviv Regional Administration, Lviv Regional Clinical Diagnostic Center, LLC “Lviv Medical Institute”, Ukrainian Society of Immu- nology, Allergology and Immunorehabilitation and the Shevchenko Scientific Society. © Svitlana Zubchenko, Olena Nadizhko, Natalya Horbal, Igor Gaiduch, 2022

7.
World Academy of Sciences Journal ; 4(4):1-6, 2022.
Article in English | Academic Search Complete | ID: covidwho-1954166

ABSTRACT

The use of convalescent plasma in coronavirus disease 2019 (COVID‑19) in the general population has not been shown to have a clear benefit. However, there are limited data available on its use in specific populations, such as in persons with human immunodeficiency virus (HIV;PWH). The present case series study describes 12 hospitalized PWH who received convalescent plasma for severe COVID‑19 between March 2020 and July 2020. Demographics, pre‑existing comorbidities, HIV status, and COVID‑19 management were reported and examined in a multivariate analysis. A high mortality rate of 58%, (7 out of 12 PWH) was observed in those receiving the convalescent plasma. By contrast, a brief review of 13 previously published cohorts of PWH hospi‑ talized with COVID‑19 revealed a cumulative mortality of 19% (85 of 439 PWH). In the present case series study, PWH had a significantly higher relative risk for in‑hospital COVID‑19‑associated mortality compared with individuals without HIV (unadjusted range, 2.10‑2.52;and adjusted range, 1.79‑2.08;P<0.02 in all analyses). Covariate‑adjustments were made for patient demographics, pre‑existing co‑morbidities, and mechanical ventilation needs. The high mortality rate of the present case series may be related to random sampling or an adverse effect of convalescent plasma in PWH and severe COVID‑19. Additional research is thus required to investigate the risks and benefits of the use of COVID‑19 convalescent plasma in PWH. [ FROM AUTHOR] Copyright of World Academy of Sciences Journal is the property of Spandidos Publications UK Ltd 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.
Cureus ; 14(4): e24438, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1954918

ABSTRACT

Introduction Classification criteria and practice guidelines for inpatient management of multisystem inflammatory syndrome (MIS) exist, but reports on outpatient management and clinical outcomes are lacking. Here we describe the management and clinical outcomes of four children and four adults with MIS seen at Walter Reed National Military Medical Center (WRNMMC) from diagnosis to six months follow-up. Methods This retrospective, case-series describes the initial presentation and management of MIS in four children and four adults seen at WRNMMC from March 2020 to September 2021. Data on each patient was collected from the time of exposure to the SARS-CoV-2 virus to six months post-diagnosis with MIS. Extracted data includes: demographics, comorbidities, initial MIS presentation, inpatient treatment, outpatient treatment, and clinical outcomes. Results A total of 62.5% of patients presented in shock. All pediatric patients received IVIG, methylprednisolone, and anakinra; no adult received this combination. Steroids and immunomodulatory medications were discontinued in 1-2 months outpatient. Three children and two adults had full symptomatic resolution. One child and two adults had persistent deconditioning at six months follow-up. One adult had persistent dyspnea. Conclusions MIS appears to be monophasic with no recurrences at six months follow-up in our patients who only required 1-2 months of glucocorticoid or immunomodulatory medications. The better outcomes in children raise the question of how much of this difference can be attributed to early combination therapy versus physiologic differences in children and adults.

9.
Elife ; 112022 07 15.
Article in English | MEDLINE | ID: covidwho-1954755

ABSTRACT

Background: Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants. Methods: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HCs) before and 7 days after the first and second vaccination. Results: OCR-treated MS patients exhibit a preserved recall response of CD8+ T central memory cells following first vaccination compared to HCs and a similar CD4+ circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2-specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4+ and CD8+ T cells. Conclusions: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8+ T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment interruptions in vulnerable patients. Funding: This research project was supported by ZonMw (The Netherlands Organization for Health Research and Development, #10430072010007), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement (#792532 and #860003), the European Commission (SUPPORT-E, #101015756) and by PPOC (#20_21 L2506), the NHMRC Leadership Investigator Grant (#1173871).


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Multiple Sclerosis , Viral Vaccines , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , Arthritis, Rheumatoid/drug therapy , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination , Viral Vaccines/genetics
10.
Front Neurol ; 13: 882905, 2022.
Article in English | MEDLINE | ID: covidwho-1952455

ABSTRACT

Although SARS-CoV-2 causes a respiratory viral infection, there is a large incidence of neurological complications occurring in COVID-19 patients. These range from headaches and loss of smell to encephalitis and strokes. Little is known about the likely diverse mechanisms causing these pathologies and there is a dire need to understand how to prevent and treat them. This review explores recent research from the perspective of investigating how the immune system could play a role in neurological complications, including cytokines, blood biomarkers, immune cells, and autoantibodies. We also discuss lessons learnt from animal models. Overall, we highlight two key points that have emerged from increasing evidence: (1) SARS-CoV-2 does not invade the brain in the majority of cases and so the associated neurological complications might arise from indirect effects, such as immune activation (2) although the immune system plays a critical role in controlling the virus, its dysregulation can cause pathology.

11.
Front Cell Dev Biol ; 10: 876180, 2022.
Article in English | MEDLINE | ID: covidwho-1952246

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been a public threat and healthcare concern caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the period of the pandemic of COVID-19, cancer patients should be paid more attention as more severe events are found in cancer patients infected with SARS-CoV-2. Basigin (BSG) is an essential factor for the infection and progression of COVID-19 and tumorigenesis of multiple tumors, which may serve as a novel target for the effective treatment against COVID-19 and multiple human cancers. Methods: A total of 19,020 samples from multiple centers were included in our research for the comprehensive investigation of the differences in BSG expression among human organs, cancer cells, cancer tissues, and normal tissues. Cox regression analysis and Kaplan-Meier curves were utilized to explore the prognosis factor of BSG in cancers. Correlation analyses were used to determine associations of BSG expression with tumor mutational burden, the immune microenvironment, etc. Gene set enrichment analysis was applied to explore the underlying mechanisms of BSG in cancers. Results: Compared with normal tissues, BSG expression was high in 13 types of cancers (cholangiocarcinoma, etc.) and low in colon adenocarcinoma and rectum adenocarcinoma. BSG expression was related to the prognosis of eight cancers (e.g., invasive breast carcinoma) (p < 0.05). The gene also demonstrated a pronounced effect in identifying 12 cancers (cholangiocarcinoma, etc.) from their control samples (AUC >0.7). The BSG expression was associated with DNA methyltransferases, mismatch repair genes, immune infiltration levels, tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoints, suggesting the potential of BSG as an exciting target for cancer treatment. BSG may play its role in several cancers by affecting several signaling pathways such as drug cytochrome metabolism P450 and JAK-STAT. Conclusion: BSG may be a novel biomarker for treating and identifying multiple human cancers.

12.
Immunotherapy ; 14(13): 1055-1065, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1952097

ABSTRACT

The human immune system protects the body against invasive organisms and kicks into a hyperactive mode in COVID-19 patients, particularly in those who are critically sick. Therapeutic regimens directed at the hyperactive immune system have been found to be effective in the treatment of patients with COVID-19. An evolving potential treatment option is therapy with mesenchymal stem cells (MSCs) due to their regenerative and reparative ability in epithelial cells. Clinical trials have reported the safe usage of MSC therapy. Systemic effects of MSC treatment have included a reduction in pro-inflammatory cytokines and a decrease in the levels of CRP, IL-6, and lactase dehydrogenase, which function as independent biomarkers for COVID-19 mortality and respiratory failure.


Treatment of COVID-19 is becoming increasingly difficult because of new variants, such as Delta, and more recently Omicron. Each virus variant becomes smarter at being able to evade the body's immune system, vaccines and drug treatments. The biggest challenge in treating COVID-19 is when the body's immune system starts to become hyperactive. In such a scenario, the immune system releases the compounds that are supposed to be released in small doses all at once. Thus, overwhelming the body and causing many complications. One possible solution to this is the mesenchymal stem cell. Multiple clinical trials have shown that mesenchymal stem cells can heal all different cell types in the body and stop the hyperactive immune system.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Humans , Immunity , Mesenchymal Stem Cell Transplantation/adverse effects , SARS-CoV-2
13.
J Immunother Cancer ; 10(7)2022 Jul.
Article in English | MEDLINE | ID: covidwho-1950234

ABSTRACT

Anti-SARS-CoV-2 antibodies are crucial for protection from future COVID-19 infections, limiting disease severity, and control of viral transmission. While patients with the most common type of hematologic malignancy, B cell lymphoma, often develop insufficient antibody responses to messenger RNA (mRNA) vaccines, vaccine-induced T cells would have the potential to 'rescue' protective immunity in patients with B cell lymphoma. Here we report the case of a patient with B cell lymphoma with profound B cell depletion after initial chemoimmunotherapy who received a total of six doses of a COVID-19 mRNA vaccine. The patient developed vaccine-induced anti-SARS-CoV-2 antibodies only after the fifth and sixth doses of the vaccine once his B cells had started to recover. Remarkably, even in the context of severe treatment-induced suppression of the humoral immune system, the patient was able to mount virus-specific CD4+ and CD8+ responses that were much stronger than what would be expected in healthy subjects after two to three doses of a COVID-19 mRNA vaccine and which were even able to target the Omicron 'immune escape' variant of the SARS-CoV-2 virus. These findings not only have important implications for anti-COVID-19 vaccination strategies but also for future antitumor vaccines in patients with cancer with profound treatment-induced immunosuppression.


Subject(s)
COVID-19 Vaccines , COVID-19 , Lymphoma, B-Cell , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , RNA, Messenger/genetics , SARS-CoV-2 , T-Lymphocytes , Vaccines, Synthetic , Viral Vaccines , mRNA Vaccines/adverse effects
14.
BMJ Open ; 12(5): e061345, 2022 05 19.
Article in English | MEDLINE | ID: covidwho-1950195

ABSTRACT

INTRODUCTION: The COmmunity Cohort Study aims to determine, after natural exposure to SARS-CoV-2 or anti-SARS-CoV-2 vaccines deployed in Chile to prevent COVID-19 in the context of the current pandemic, the strength and duration of detectable neutralising antibodies in adult ambulatory primary care patients with cardiovascular risk factors. METHODS AND ANALYSIS: We will set up a community-based longitudinal, prospective cohort study. The study will be conducted in two public outpatient clinics located in the southern district of Santiago, Chile. We expect to begin recruitment in the second quarter of 2022. Each patient will be followed up for at least 1 year after inclusion in the cohort. The eligible population will be adult patients registered in the Cardiovascular Health Programme. Exposure in this study is defined as any event where participants have contact with SARS-CoV-2 antigens from natural exposure or vaccination. The primary outcomes are seroconversion and strength and duration of the neutralising IgG antibodies to SARS-CoV-2. Secondary outcomes are any COVID-19-related event or intercurrent morbidities or death. Data will be collected by extracting serial blood samples and administering a questionnaire at the first face-to-face contact and monthly follow-up time points. The sample size estimated for this study is 1060. We will characterise the cohort, determine the seroprevalence rate of neutralising antibodies at baseline and determine the rates of antibody decline using a longitudinal mixed-effects model. ETHICS AND DISSEMINATION: The Scientific Ethics Committee of the South Metropolitan Health Care Service approved the study protocol (Memorandum No 191/2021). We will present the results in two peer-reviewed publications and national and international professional and academic meetings. We will organise seminars with relevant stakeholders and hold town hall meetings with the local community. We will set up a COmmunity Cohort Study website at www.communitystudy.cl to disseminate the study purpose, research team and milestones.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , COVID-19/epidemiology , Cohort Studies , Humans , Immunity, Humoral , Prospective Studies , Seroepidemiologic Studies
15.
BMJ Open ; 12(7): e056370, 2022 07 18.
Article in English | MEDLINE | ID: covidwho-1950151

ABSTRACT

OBJECTIVES: Dynamics of antibody responses following SARS-CoV-2 infection are controversial in terms of immunity and persistence. We aimed to assess longitudinally the trend of antibody serological titres, their correlation with clinical severity as well as clinical reinfection during a follow-up. DESIGN: Longitudinal cohort, 12 months follow-up study. SETTING: USL Umbria 2. PARTICIPANTS: Consecutive subjects aged 15-75 who were discharged with the diagnosis of Sars-Cov-2 from the hospitals of the AUSL Umbria 2, or resulted positive to a PCR test for SARS-CoV-2 infection with or without symptoms were recruited. SARS-CoV-2 serological testing for antibodies targeting the Nucleocapside and Spike proteins were determined. RESULTS: Of 184 eligible subjects, 149 were available for evaluation: 17 were classified as oligo/asymptomatic, 107 as symptomatic, 25 as hospital admitted. Participants differed in terms of signs and symptoms as well as treatment. Overall there was a significant difference in terms of antibody titres between groups (anti-S: p<0.00; anti-N: p=0.019). Median anti-S titres in the symptomatic and hospital admitted participants were significantly higher compared with the oligo/asymptomatic participants. During follow-up, the median titre of anti-S antibodies did not show significant variations (p=0.500) and the difference within groups remained constant overtime. Subjects that showed an anti-S titre above the threshold of 12 U/mL were 88.7% at first visit and 88.2% at last follow-up. Anti-N values were higher in the hospital admitted participants compared with the other two groups. Anti-N titre reduced constantly overtime (p<0.001) and across the three groups of participants. The percentage of the subjects with serological titre above threshold (<1.4 U/mL) decreased from 74.5%% to 29.2% (p<0.001). None of the participants developed clinically evident reinfection. CONCLUSION: Anti-N and anti-S correlate well with clinical severity. While anti-N declines overtime, anti-S antibodies persist for at least 1 year.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , COVID-19/diagnosis , Follow-Up Studies , Humans , Longitudinal Studies , Reinfection
17.
J Allergy Clin Immunol Pract ; 2022 May 23.
Article in English | MEDLINE | ID: covidwho-1945417

ABSTRACT

The use of telemedicine has increased in allergy/immunology, with rapid uptake of its use during the coronavirus disease 2019 pandemic. Existing data indicate an overall positive view of telemedicine by patients, particularly during the coronavirus disease 2019 pandemic. However, patients and clinicians prefer in-person visits for specific types of allergy/immunology encounters, such as those requiring a physical examination or diagnostic testing. The most data for telemedicine exist with asthma, and provide a model for treatment technique, therapeutic monitoring, and education in other allergic and immunologic conditions. Clinician satisfaction is also necessary for telemedicine to be an enduring option for patient/clinician interactions, and this is influenced by a multitude of factors, including technology quality, reimbursement, and maintenance of patient/clinician relationships. Areas of future research should include the need for more outcome data in additional disease states, which will likely help facilitate improved logistical policies around telemedicine that would facilitate its adoption.

18.
iScience ; 25(7): 104549, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1945338

ABSTRACT

We report robust SARS-CoV2 neutralizing sdAbs targeting the viral peptides encompassing the polybasic cleavage site (CSP) and in the receptor binding domain (RBD) of the spike (S) protein. Both the sdAbs inhibited infectivity of the CoV2 S protein expressing pseudoviruses (LV-CoV2S). Both anti-CSP and RBD intrabodies (IB) inhibited the output of LV(CoV2 S). Anti-CSP IB altered the proteolytic processing and targeted the viral S protein for degradation. Because of cross-reactive CSPs in the entry mediators, the anti-CSP sdAb neutralized in vitro and in vivo the infectivity of SARS-CoV2 unrelated viruses such as herpes simplex virus 1 (HSV1) and pestes des petits ruminants virus (PPRV). Conversely, anti-HSV1 and anti-PPRV sera neutralized LV(CoV2 S) owing to the presence of CSP reactive antibodies indicating that a prior infection with such pathogens could impact on the pattern of COVID-19.

19.
Cell Rep ; 40(4): 111138, 2022 Jul 26.
Article in English | MEDLINE | ID: covidwho-1944467

ABSTRACT

COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8+ T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8+ T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer+ cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%-65.6% (23.0% on average) of the peak. MHC-I multimer+ cells dominantly exhibit phenotypes of activated effector cells 1-2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (TSCM) cells. Importantly, the frequency of TSCM cells 1-2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8+ T cells, indicating that early generation of TSCM cells determines the longevity of vaccine-induced memory CD8+ T cell responses.


Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Stem Cells , Vaccination
20.
Cell Rep ; 39(13): 111004, 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1944462

ABSTRACT

Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.


Subject(s)
COVID-19 , SARS Virus , Single-Domain Antibodies , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Humans , SARS-CoV-2
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