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1.
Vnitrni Lekarstvi ; 68(5):290-294, 2022.
Article in Czech | EMBASE | ID: covidwho-2010607

ABSTRACT

A case report of a patient with newly diagnosed granulomatosis with polyangiitis (GPA) after undergoing COVID-19 (Coro-navirus Disease 2019) is discussed. GPA is one of the ANCA-associated vasculitis, which is characterized by the presence of autoantibodies against cytoplasmic enzymes neutrophils (Anti Neutrophil Cytoplasmatic Antibodies). It is a vasculitis that mainly affects small blood vessels, leading to damage to the kidneys, lungs, and upper respiratory tract, including the paranasal sinuses and orbits. This disease can result in an acute life-threatening condition. Such complications include diffuse alveolar hemorrhage (DAH), a condition characterized by blood leakage from the pulmonary vessels into the alveoli, often leading to acute vital signs and even respiratory failure. DAH can have many causes – autoimmune diseases including vasculitides as well as non-immunological causes. Early and adequate comprehensive therapy including immunosuppressive treatment (cyclophosphamide/rituximab and glucocorticoids) can be life-saving.

2.
Journal of Kerman University of Medical Sciences ; 29(4):368-377, 2022.
Article in English | EMBASE | ID: covidwho-2010569

ABSTRACT

Background: The COVID-19 pandemic is a red alarm for global health, so researchers around the world are working on it to design an effective vaccine against it. Protein is one of the candidates for vaccine development which plays an important role in virus pathogenesis. Accordingly, this study was done to evaluate the critical characteristic of this protein as a vaccine candidate using in-silico analysis. Methods: The sequence of SARS-CoV-2-associated E protein was recruited from NCBI and subjected to the IEDB software to evaluate the most potent epitopes. The capacity of the interactions of HLA-I and HLA-II molecules with selective peptides was studied using IEBD tool kit. The E protein sequence was subjected to B cell and T cell tests to realize the most promising peptides that could act as COVID-19 vaccine. Results: Among the tested peptides for the T cell-test, this study found two interesting epitopes: VSEETGTLI and LTALRLCAY that exhibit high binding affinity as a strong indicator to HLA-I and HLA-II alleles together. The results of the analysis demonstrated that some epitopes in the E protein have a relatively higher immunogenicity score based on interaction with HLA-II, such as SEETGTLIVNSVLLF, TLIVNSVLLFLAFVV, LAFVVFLLVTLAILT, LAILTALRLCAYCCN, and SVLLFLAFVVFLLVT. Furthermore, two sequences (FVSEET and PSFYVYSRVKNLNSSRVP) were reported as the selective linear epitopes for B cell, on the surface of SARS-CoV-2 E protein and being Immunogenic. Conclusion: Since E protein can stimulate favorable immune responses, T and B-cell responses, its evaluation in patients with COVID-19 is of a great importance.

3.
Journal of Xi'an Jiaotong University (Medical Sciences) ; 43(5):797-801, 2022.
Article in Chinese | EMBASE | ID: covidwho-2010485

ABSTRACT

Objective: To compare the clinical features of Omicron and Delta cases, so as to provide scientific basis for the prevention and treatment of COVID-19. Methods: The case-control study method was used to retrospectively analyze the clinical data of the Omicron cases admitted to the designated hospital for the treatment of COVID-19 in Xi'an from December 2021 to January 2022. and the Delta cases admitted during the same period were used as the control group. The demographic data, epidemiological history, vaccination status, clinical characteristics, laboratory tests, nucleic acid and antibody levels, and outcomes of patients in the two groups were collected and compared. Results: A total of 21 patients were included in the study, 5 were Omicron patients and 16 were Delta cases. The mean age of the patients in the two groups were (38.20±15.07) and (37.69±10.39) years, respectively.The time interval between the last vaccination and the diagnosis was (145.40±77.92) days and (159.00±99.74) days, respectively. For the initial symptoms, the patients with Omicron were mainly characterized by throat discomfort (3, 60%), cough and sputum (2, 40%), and the patients with Delta were mainly characterized by throat discomfort (5, 31.25%), fatigue (5, 31.25%), cough and sputum (4, 25%). On admission, laboratory tests showed that 60% of Omicron patients had low lymphocytes and elevated erythrocyte sedimentation rate, and 50% of patients in the delta group had elevated hemoglobin. The Ct values of ORFlab gene, N gene and E gene with Omicron were lower than those with Delta. And the difference of E gene between the two groups was statistically significant (t=-2.711, P=0.024). IgG antibody levels increased in both groups.The time for nucleic acid to turn negative with Omicron was (28.20±5.89) days, and it was (18.50±7.73) days with Delta, and the difference between the groups was statistically significant (t=2.565, P=0.019). The length of hospitalization with Omicron was (30.60±4.88) days, and that with Delta was (22.13±7.81) days, and the difference was statistically significant (t=2.270, P =0.035). Conclusions: The initial symptoms of Omicron patients are mainly throat discomfort, cough and sputum. The clinical manifestations are generally mild. The nucleic acid test Ct value is lower. The time for nucleic acid to turn negative and the time for hospitalization are longer, and the potential infectiousness is stronger. Those eligible for vaccination should complete the full course of vaccination and booster vaccination as soon as possible. At the same time, the management of "early detection, early reporting, early isolation, and early treatment" should be implemented.

4.
Cocuk Enfeksiyon Dergisi ; 16(2):87-94, 2022.
Article in English | EMBASE | ID: covidwho-2010459

ABSTRACT

Objective: It is thought that hyperinflammation has an important role in the pathogenesis of severe COVID-19 and tests that determine the de-gree of inflammation can be used to predict the severity of the disease. From this point of view, we aimed to determine the hematological parameters that can predict the severity of COVID-19 in pediatric patients. Material and Methods: Symptomatic and SARS-CoV-2-PCR test positive 105 children were included to study. Seventy-nine patients had mild, 26 had moderate to severe COVID-19 at admission. Data about their demo-graphic characteristics, clinical and laboratory findings were collected from their medical records. Correlations between the hematological parameters and disease severity of patients were investigated by using uni-variate and multivariate regression analyses. Predictive value of different diagnostic markers was studied. Results: Mean age was older (177 months vs. 70 months) and mean body mass index (BMI) was higher (18.8 kg/m2 vs. 25.0 kg/m2) in patients with severe COVID-19 than those with mild. Univariate analysis showed that mean leucocyte (WBC), lymphocyte, eosinophiles, and platelet counts were lower;mean platelet volume (MPV), neutrophil to lympho-cyte ratio (NLR), and derived neutrophil to lymphocyte ratio (dNLR) were higher in severe COVID-19 group (p< 0.05). Multivariant analysis showed low lymphocyte (OR 0.072) and WBC count (OR 0.085), high dNLR (OR 2.14) and MPV (OR 2.35) indexes were the most valuable parameters to predict disease severity, ROC curve analysis revealed lymphocyte count has superior predictive value (<1.55 /mm3 has 84.6% sensitivity, 70.9% specificity) than other CBC parameters have. Conclusion: Low lymphocyte and leukocyte count, high MPV and dNLR values have significant predictive value in predicting COVID-19 severity. In particular, lymphopenia appears to be a valuable parameter to identify patients at high risk for severe disease and initiate accurate treatment to prevent disease deterioration.

5.
Cocuk Enfeksiyon Dergisi ; 16(2):77-86, 2022.
Article in English | EMBASE | ID: covidwho-2010458

ABSTRACT

Objective: Multisystem inflammatory syndrome (MIS-C) in children is a newly defined and serious health problem that develops after SARS-CoV-2 infection. Our aim is to report epidemiological, clinical, laboratory and radiological features of children with MIS-C. Material and Methods: Forty patients who applied to our hospital from October 2020 to February 2021 and met the MIS-C criteria were included in the study. Patients with gastrointestinal involvement (GIS), cardiac involvement and Kawasaki Disease (KD)-like MIS-C were examined clini-cally and laboratory. Results: The mean age of the patients was 8.2 ± 4.2 years and male patients were in the majority (70%). The most common symptoms were fe-ver (100%) and fatigue (90%). Gastrointestinal symptoms were present in 71%, cardiac involvement in %40, Kawasaki-like patients in %52.5, shock symptoms in 59%. Elevated levels of C-reactive protein, D-dimer, and ferritin were found in 100%, 97.5%, and 67.5% of the patients, respec-tively. Patients with cardiac involvement had higher mean age and lower lymphocyte levels. Shock findings were higher in patients with KD-like MIS-C. Also, INR and ferritin levels were higher in KD-like MIS-C patients (p= 0.028). The mean platelet count (p= 0.004) and albumin levels were lower (p= 0.048) in shock group. Conclusion: MIS-C is a hyperinflammatory syndrome with cardiac, GIS, and lung involvement. Cardiac findings were not common in patients presenting with KD-like MIS-C, but a poor prognosis was observed in KD-like MIS-C patients. Patients with cardiac involvement were older and their lymphocyte count was lower.

6.
Frontiers in Microbiology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009881

ABSTRACT

The rapid spread of the SARS-CoV-2 virus and its variants has created a catastrophic impact worldwide. Several variants have emerged, including B.1.351 (Beta), B.1.1.28/triple mutant (P.1), B.1.1.7 (Alpha), and B.1.429 (Epsilon). We performed comparative and comprehensive antigenicity mapping of the total S-glycoprotein using the Wuhan strain and the other variants and identified 9-mer, 15-mer, and 20-mer CTL epitopes through in silico analysis. The study found that 9-mer CTL epitope regions in the B.1.1.7 variant had the highest antigenicity and an average of the three epitope types. Cluster analysis of the 9-mer CTL epitopes depicted one significant cluster at the 70% level with two nodes (KGFNCYFPL and EGFNCYFPL). The phage-displayed peptides showed mimic 9-mer CTL epitopes with three clusters. CD spectra analysis showed the same band pattern of S-glycoprotein of Wuhan strain and all variants other than B.1.429. The developed 3D model of the superantigen (SAg)-like regions found an interaction pattern with the human TCR, indicating that the SAg-like component might interact with the TCR beta chain. The present study identified another partial SAg-like region (ANQFNSAIGKI) from the S-glycoprotein. Future research should examine the molecular mechanism of antigen processing for CD8+ T cells, especially all the variants’ antigens of S-glycoprotein.

7.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009867

ABSTRACT

The immune system generates memory cells on infection with a virus for the first time. These memory cells play an essential role in protection against reinfection. Tissue-resident memory T (TRM) cells can be generated in situ once attacked by pathogens. TRM cells dominate the defense mechanism during early stages of reinfection and have gradually become one of the most popular focuses in recent years. Here, we mainly reviewed the development and regulation of various TRM cell signaling pathways in the respiratory tract. Moreover, we explored the protective roles of TRM cells in immune response against various respiratory viruses, such as Respiratory Syncytial Virus (RSV) and influenza. The complex roles of TRM cells against SARS-CoV-2 infection are also discussed. Current evidence supports the therapeutic strategies targeting TRM cells, providing more possibilities for treatment. Rational utilization of TRM cells for therapeutics is vital for defense against respiratory viruses.

8.
Infection and Drug Resistance ; 15:5111-5120, 2022.
Article in English | EMBASE | ID: covidwho-2009773

ABSTRACT

Purpose: We evaluated the differences between patients with SARS-CoV-2 Omicron variant infections and Fever outpatients, so that prevention and control measures can be taken in time. Patients and Methods: This study retrospectively analyzed 65 patients with SARS-CoV-2 Omicron variant. Sixty-nine age-and sex-matched Fever outpatients were enrolled during the same period of time. We also reanalyzed data from 81 SARS-CoV-2 Wild-Type-infected patients. We compared the clinical characteristics and initial indexes of routine tests among the 3 groups. Results: A total of 93.8% of the patients with Omicron infections had clinical symptoms, and the major symptoms were cough, fever and pharyngalgia. Pharyngalgia was a specific manifestation in Omicron group compared to Wild-Type group. The white blood cell of the Omicron group was lower than that of the Fever group [5.0 (3.6–6.1) vs 10.1 (7.6–12.9) ×109/L, P < 0.001]. The neutrophil count in Omicron group was lower than that in Fever and Wild-Type group [2.6 (1.8–3.9) vs 8.1 (5.9–10.9), P < 0.001;2.6 (1.8–3.9) vs 3.4 (2.5–4.7) ×109/L, P < 0.001]. The white blood cell and neutrophil counts were lower in Omicron group than in the Fever group. The top 5 major symptoms were fever, cough, pharyngalgia, headache and expectoration. Conclusion: There are differences between the patients with Omicron infections and Fever outpatients, both in clinical manifestations and initial routine hematology indicators. We hope to provide some clues for early identification combined with a history of living in the epidemic area.

9.
Biomolecular concepts ; 13(1):298-313, 2022.
Article in English | MEDLINE | ID: covidwho-2009730

ABSTRACT

Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein interaction partners of signaling hubs and network analysis of common partners and their expression analysis might lead to the identification of critical nodes in cellular signaling. A pairwise comparison of signaling hubs across several related pathways might reveal novel signaling modules. Analysis of protein interaction connectome by Venn (PIC-Venn) of transcription factors STAT1, STAT3, NFKB1, RELA, FOS, and JUN, and their common interaction network suggested that BRCA1 and TSC22D3 function as critical nodes in immune responses by connecting the signaling hubs into signaling modules. Transcriptional regulation of critical hubs may play a major role in the lung epithelial cells in response to SARS-CoV-2 and in COVID-19 patients. Mutations and differential expression levels of these critical nodes and modules in pathological conditions might deregulate signaling pathways and their target genes involved in inflammation. Biological connectivity emerges from the structural connectivity of interaction networks across several signaling hubs in related pathways. The main objectives of this study are to identify critical hubs, critical nodes, and modules involved in the signal transduction pathways of innate and adaptive immunity. Application of PIC-Venn to several signaling hubs might reveal novel nodes and modules that can be targeted by small regulatory molecules to simultaneously activate or inhibit cell signaling in health and disease.

10.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009641

ABSTRACT

Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID- 19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID- 19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting.

11.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009640

ABSTRACT

Background: Second allogeneic hematopoietic cell transplant (sAHCT) might be indicated following a graft failure or disease relapse after the first one;although it might emerge with high rates of morbidities and mortality. Currently, there is a limited number of publications on this matter in the literature, here we aimed to share our sAHCT experience from a single center. Methods: Data from 51 patients who were eligible for sAHCT between 2001 and 2021 was evaluated retrospectively. All data was obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Results: 51 patients were included in the present study. Median age at sAHCT was 34 (18- 65) and female/ male ratio 19/ 32 (37.3% / 62.7%). The same donor from the first transplant was eligible for sAHCT for most patients (n= 46, 90.2 %). sAHCT indication was graft failure for 11 patients (21.6 %) whereas 40 (78.4 %) patient went on sAHCT for disease relapse. Patients' diagnoses were as follows: acute myeloid leukemia (n= 26, 50.9 %), acute lymphoblastic leukemia (n=9, 17.6 %), myelodysplastic syndrome (n= 6, 11.8 %), aplastic anemia (n= 6, 11.8 %) and others (CMML, CML, biphenotypic leukemia). Median number of transplanted CD34+ hematopoietic cells was 5.77 x x106/ kg (1.11- 8.29). Stem cell source was either bone marrow (n= 5, 9.8%) or peripheral blood (n= 46, 90.2 %). Myeloablative conditioning regimens were used for most sAHCTs (n= 30, 58.8%). Median overall survival (OS) rates for graft failure and disease relapse groups were 12.8 and 18.7 months, respectively (p= 0.63). During early transplant phase, 20 patients (39.2 %) died due to bone marrow aplasia, transplant failure or other complications. 1 year OS of the entire cohort was 33.3 % whereas 2-y- OS was 21.6% (95% CI= 25-45). 2 patients (3.9 %) died due to COVID19 during transplant process. On univariate analysis, sex, time from the first transplant (<12 months/ ≥12 months), conditioning intensity, sAHCT indication did not statistically significantly influence OS. Multivariate analysis confirmed a lower ECOG score (<2) at sAHCT significantly increased OS (p= 0.001). Conclusions: Based on this single center study, sAHCT is an efficacious treatment modality especially for patients with lower ECOG scores. sAHCT may offer long term survival for both graft failure and disease relapse states.

12.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009639

ABSTRACT

Background: Preclinical data indicate that anti-PD-1 agents can facilitate activity of bispecific T-cell engager (BiTE) molecules. Here we assess the combination of the anti-CD19 BiTE molecule blinatumomab with the anti-PD-1 antibody AMG 404 in adults with R/R ALL (NCT04524455). Methods: Eligible adults with R/R ALL (Ph+ disease included) received 2-5 treatment cycles. Each cycle was 42 days, consisting of 4 weeks of cIV blinatumomab and a 2-week treatment-free interval as per label. In Cohort 1, AMG 404 was dosed IV at 240 mg every 4 weeks (Q4W);first dose was Day (D) 11 of Cycle (C) 1. Primary endpoints were dose-limiting toxicities (DLTs) and other adverse events (AEs). Results: As of 20 Dec 2021, patients (pts) from Cohort 1 (n=8) had median age of 57 (range: 24-73) y, 6/ 8 male, 6/8 Caucasian, 1 with extramedullary disease (duodenum), 2 with prior blinatumomab, and a median of 5 (2-15) prior treatment lines. Two pts remain on study and 2 completed the study;4 pts discontinued the study due to death (n=3) or consent withdrawn (n=1). No DLTs were reported for the 3 evaluable pts. Of the 5 pts not evaluable for DLTs, in C1, 4 had disease progression and 1 an unrelated fatal pneumonia. Treatment-related grade (Gr) ≥3 and/or serious AEs in all 8 pts included cytokine release syndrome (CRS) (1 pt Gr 2, 1 pt Gr 1 and 3), Gr 3 increases in ALT and AST, Gr 3 fever, Gr 3-4 neutropenia, Gr 4 neutropenia/Gr 3-4 thrombocytopenia (same pt), Gr 2 sensorimotor polyneuropathy, Gr 3 hypertension, Gr 3 encephalopathy, and in 1 pt Gr 3-4 decreases in white blood cells, lymphocytes, and neutrophils. One pt developed Gr 3 SARS-COV-2 pneumonia on C2D25, resolving without clinical sequelae. C3 start was delayed by 12 days but protocol treatment resumed uneventfully. All 3 DLT-evaluable pts had a complete response (CR) or CR with partial hematologic recovery (CRh), 2/3 without measurable residual disease (MRD), within 2 cycles;the 3rd pt had an MRD response at the end of C3. Preliminary pharmacokinetic results for the combination of blinatumomab and AMG 404 demonstrated that their exposures were consistent with those observed for each as monotherapy and did not indicate any drug-drug interactions. To date, all samples tested for anti-blinatumomab antibodies have been negative. Conclusions: In this ongoing phase 1b study, the combination of blinatumomab with AMG 404 was tolerated with a manageable safety profile. No DLTs were reported. Enrollment continues in Cohort 2 in which AMG 404 is dosed Q4W at 480 mg starting on C1D1, 48 hours prior to blinatumomab.

13.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009628

ABSTRACT

Background: Some known viral infections can lead to a diagnosis of cancer (e.g: HPV, HIV, EBV, etc.) Anecdotical reports of a Covid 19 infection, and the subsequent diagnosis of a new cancer have been mentioned by few patients (pts). This relationship has not yet been fully documented. Covid 19 infected persons have been identified to have a suppressed adaptive immunity, which one of its principal functions is to maintain occult cancer cells in an equilibrium state. We studied the possible role of a Covid 19 infection and the subsequent diagnosis of a new primary cancer happening during the Covid pandemic (01/2020 - 12/2021). A survey was sent to all new members of Belong.life, a free and anonymous global cancer app for pts and their caregivers. This study took place prior to the omicron variant surge. Methods: 2579 Belong.life members received randomly, in the app various cancer groups, a 10 questions voluntary survey regarding the onset of a Covid 19 infection and the development of a subsequent new primary cancer diagnosis. 262 replied of whom 124 fulfilled the eligibility criteria and confirmed having had a Covid 19 infection followed by a new cancer diagnosis. Data on the 124 pts was analyzed by Belong analysts, according to age, sex, geographical distribution, Covid 19 infection onset and type and timing of the cancer diagnosis. Results: Most pts were USA based (102/124, 82%), and 1/3 were < 49 years, followed by a 1/3 in the 50-59 and > 60 groups. 71% (88/ 124) were females. All had a prior Covid 19 infection and only 14 (11%) required hospitalization. 109/124 (88%) had a primary cancer diagnosis and 15 (12%) had disease recurrence. Breast cancer was diagnosed in 38% (47/124), followed by lung and gynecological cancers (10/124, 8% respectively). Time from Covid 19 infection to primary cancer diagnosis was < 6 months in 57 /124 (46%) and 6-12 months in 40/124 (32%). Breast cancer developed earlier (< 12 months) in 87% of the pts. In total 97/124 (78%) pts had their disease diagnosed within less than a year. Conclusions: Known viruses might precede the onset of a new cancer. The role of corona viruses and subsequent development of a cancer is unknown. Adaptive immunity maintains occult cancer cells in a steady state, while a Covid 19 infection interferes with it, causing a weak and delayed immune response, which could be responsible, after a period, for the onset of a new primary cancer. We are presenting RWD on 124 pts with new primary cancers diagnosed after a Covid 19 infection. This represents a 5% incidence in a random pts group (124/2579) as described above. Further studies should be planned to investigate this real world increased incidence and testing of the diverse immune parameters are also warranted to further understand the intersection pathways of Covid 19 infection and cancer development.

14.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009622

ABSTRACT

Background: Data on SARS-CoV-2 infections in oncological patients in the outpatient settings are scarce. Methods: During the spread of the delta variant between April 2021 and September 2021, a total of 10.677 patients were tested for SARS-CoV-2 infection by RT-qPCR in seven outpatient clinics in Bavaria, Germany. Results: Within the tested patient cohort, 4.960 patients (46.5%) suffered from a malignant disease (74% solid tumors and 26% malignant hematological diseases). This group was compared with 5.717 patients (53.5%) without a malignant disease (33.1% with other hematological diseases and 66.9% patients without a hematological or oncological disease). During the observation period, 119 (2.4%) patients with malignancies were tested positive (88 patients with solid tumors;31 patients with malignant hematological diseases) compared to 115 positive patients (2.0%) in the control group. 32 of 119 positively tested patients (26.9%) suffering from malignant disease required hospitalization and 9/32 patients (28.1%) died during the clinical course. Conclusions: These observations are in clear contrast to data from patients we evaluated during the pre-delta variants period between 15 and 26 April 2020 in the same seven outpatient clinics. In this period, a total of 1.227 patients were tested for SARS-CoV-2 by RT-qPCR. 78/1227 patients (6.3%) were tested positive in RT-qPCR and most showed mild symptoms of infection. None of the SARS-CoV-2 infected patients died. These data were analyzed when no vaccination was available. These data were evaluated during a period where no vaccine was available. Vaccination of patients with malignancies with BiontechPfizer's mRNA vaccines was started in April 2021. The response to the vaccine was tested by an antibody assay (Elecsys Anti-SARS-CoV-2 S-immunoassay, Roche) at the earliest four weeks after the second vaccination. To assess the response, we compared five patient cohorts: Patients who received (i) B cell depleting antibodies, (ii) checkpoint inhibitors (ICI), (iii) chemotherapy, or (iv) tyrosin kinase inhibitors (TKIs), and (v) healthy controls. The patients treated with ICI or TKI showed a comparable vaccination response to the healthy patients, while patients receiving Rituximab/Obinutuzumab showed no significant humoral vaccination response at all. The more severe disease course of patients infected by the SARS-CoV-2 delta variant compared to the initial waves of infections strongly underline the importance of vaccination in cancer patients.

15.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009606

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) has been nominated as a pandemic by the World Health Organization short after has spreaded globally. Unfortunately, even after several effective vaccines approved by FDA, COVID-19 cases are still surging. Compared to the general population, patients with cancer are more susceptible to COVID-19 for many aspects. Therefore, better understanding of the clinical characteristics of cancer patients with COVID-19 is urgently needed to spare these vulnerable patients from severe disease course. Methods: This retrospective study was completed in Capital Health Regional Medical Center, New jersey, USA. Adult patients with COVID-19 diagnosed between March 2020 and May 2021 were included in this study. All selected COVID-19 patients were stratified as two groups: Patients with cancer and patients without cancer. Other variables were included as age at diagnosis, gender, race/ethnicity, insurance status, obesity, comorbidity score, treatment of COVID-19, oxygen requirement and vital status. The Charlson Comorbidity Index was used to calculate the comorbidity score. Results: A total of 562 COVID-19 patients were included in this study;67 (12%) patients diagnosed with cancer. Patients with cancer were more likely to be older (73 vs. 62 years, p < 0.001), overweight (BMI 25-29.9) (39% vs 28%, p = 0.02), and have higher comorbidity score > 3 (58% vs 15%, p < 0.001) than patients without cancer. Patients with cancer more frequently received steroid therapies (52% vs. 34%, p = 0.003), remdesivir (21% vs. 4%, p < 0.001), and convalescent plasma (21% vs. 10%, p = 0.009). The rate of high flow oxygen therapy was higher in patients with cancer than patients without cancer (30% vs. 16%, p = 0.02). The days of mechanic ventilation, hospital stay, ICU admission were similar between two groups. Patients without cancer had better survival rate compared to patients with cancer (77% vs. 64%, p = 0.02). Patients with cancer had increased D-dimer level (2.4 vs. 1.6 mg/L, p = 0.08) compared to patients without cancer but it was not significantly different. Other laboratory findings were also similar between two groups, including WBC, neutrophils, lymphocytes, lactate, lactate dehydrogenase, creatine kinase, d-dimer, C-reactive protein, procalcitonin, fibrinogen, BNP, troponin, sodium, AST, ALT, and ferritin. Multivariable logistic regression analysis showed that patients with cancer were associated with increased odds of higher than 3 comorbidity score (OR 7.09 [3.85-13.05], p < 0.001) and oxygen therapy with nasal cannula up to 6 liters (OR 3.7 [1.04-13.5], p = 0.04). Conclusions: This present analysis showed that patients had increased risk of mortality compared to counterpart. Our results emphasize that cancer patients as a group are at higher risk due to advanced age and preexisting conditions.

16.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009568

ABSTRACT

Background: CDK4/6 inhibitors showed a favorable progression-free survival (PFS) in DD LPS, a sarcoma bearing 12q 13-15 amplicon that implies CDK4 amplification. The median PFS was 4 and 7 months (m) for palbociclib and abemaciclib, respectively. Preclinical experiments in 10 sarcoma cell lines and 6 PDX models, including only one DD LPS, showed higher efficacy of anti-CDK4 in cases with high expression of CDK4 and low expression of p16. This rationale supported the design of a phase II trial exploring palbociclib in a wide range of sarcomas, excluding DD LPS. Methods: Progressing pretreated advanced soft tissue sarcoma, excluding DD LPS, or osteosarcoma adult patients (pts), whose tumors overexpressed CDK4 and underexpressed CDKN2A mRNA in a baseline mandatory biopsy, were enrolled. CDK4 and CDKN2A expression were assessed by qRT-PCR, using an external control as reference (Universal human reference RNA;Agilent Technologies). The primary endpoint was 6-m PFS rate. Minimax Simon's two-stage with type 1 and 2 errors of 10%, and null and alternative hypothesis of H0 15%, H1 40%, 6-month PFS rates were specified. The study will warrant further investigation if 6 or more pts had a PFS > 6 m from 21 evaluable pts. Palbociclib was administered orally at 125 mg/ day 21 out of 28 days. Pre-screening intended to increase the probability of positive profile in the baseline biopsy. Results: A total of 214 pts with 236 CDK4/ CDKN2A determinations were assessed for enrolment;141 for prescreening, in archive tumor sample, and 95 for screening, in a baseline biopsy. There were 38/141 (27%) and 28/95 (29%) pts with favorable mRNA profile from pre and screening, respectively. Twenty-two pts were enrolled with a median of previous systemic lines of 3 (1- 5). There were 9 different sarcoma subtypes, including 2 osteosarcomas. With a median FU of 10 m (0.4-23.3), the median PFS was 4.2 m (95% CI 0.9-7.4), while the 6- and 12-m PFS rates were 30% (95% CI 9-51) and 18% (95% CI 12-48) respectively. From 19 evaluable pts (1 early death by COVID, 1 withdrew consent and for 1 it was too early to be assessed) 11 had stable disease (58%) and 8 progressed (42%) as the best response. Patients with CDK4 expression above the median value had significantly longer mPFS in the univariate analysis: 5.9 m (95% CI 1.4-10.4) vs 1.9 m (95% CI 0.6- 3.2), p = 0.046;and longer OS: 15.5 m (95% CI 6.8-24.3) vs 10.6 m (95% CI 0-23.2), p = 0.047, respectively. The probability to find a positive profile in the screening was 29%, but this proportion increased up to 41% if in pre-screening had been positive. Conclusions: Palbociclib showed to be effective in a wide variety of sarcoma subtypes, other than DD LPS, selected by CDK4/CDKN2A biomarkers.

17.
Therapeutic Advances in Vaccines and Immunotherapy ; 10, 2022.
Article in English | EMBASE | ID: covidwho-2009344

ABSTRACT

While antibodies garner the lion’s share of attention in SARS-CoV-2 immunity, cellular immunity (T cells) may be equally, if not more important, in controlling infection. Both CD8+ and CD4+ T cells are elicited earlier and are associated with milder disease, than antibodies, and T-cell activation appears to be necessary for control of infection. Variants of concern (VOCs) such as Omicron have escaped the neutralizing antibody responses after two mRNA vaccine doses, but T-cell immunity is largely intact. The breadth and patient-specific nature of the latter offers a formidable line of defense that can limit the severity of illness, and are likely to be responsible for most of the protection from natural infection or vaccination against VOCs which have evaded the antibody response. Comprehensive searches for T-cell epitopes, T-cell activation from infection and vaccination of specific patient groups, and elicitation of cellular immunity by various alternative vaccine modalities are here reviewed. Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed. While VOCs have not yet fully escaped T-cell immunity elicited by natural infection and vaccines, some early reports of partial escape suggest that future VOCs may achieve the dreaded result, dislodging a substantial proportion of cellular immunity, enough to cause a grave public health burden. A proactive, rather than reactive, solution which identifies and targets immutable sequences in SARS-CoV-2, not just those which are conserved, may be the only recourse humankind has to disarm these future VOCs before they disarm us.

18.
Journal of the Intensive Care Society ; 2022.
Article in English | EMBASE | ID: covidwho-2009322

ABSTRACT

Introduction: This study aims to assess the association between mean platelet volume (MPV) and poor outcome in patients with COVID-19. Methods: We performed a comprehensive literature search using the PubMed, Embase and Scopus databases with keywords “2019-nCoV” OR “SARS-CoV-2” OR “COVID-19” AND “mean platelet volume” OR “MPV” on 8 July 2021. The primary outcome was composite poor outcome, defined as severe COVID-19 or mortality. The pooled effect estimate was reported as mean differences in terms of MPV between the group with and without outcome. Results: There were 17 studies which consist of 4549 patients with COVID-19 were included in this study. The incidence of poor outcome was 25% (20%–30%). Mean MPV was found to be higher in the poor outcome group in compare to no poor outcome group (10.3 ± 1.9 fL vs 9.9 ± 1.7 fL). The mean MPV difference between both group was 0.47 fL [95% CI 0.27, 0.67], p < 0.001;I2: 62.91%, p < 0.001). In the sub-group analysis, patients with severe COVID-19 had higher MPV (mean difference 0.54 fL [95% CI 0.28, 0.80], p < 0.001;I2: 54.84%, p = 0.014). Furthermore, MPV was also higher in the mortality group (mean difference 0.54 fL [95% CI 0.29, 0.80], p = 0.020;I2: 71.11%, p = 0.004). Meta-regression analysis showed that the association between MPV and poor outcome was not affected by age (p = 0.789), gender (p = 0.167), platelets (p = 0.056), white blood cells (p = 0.639), and lymphocytes (p = 0.733). Conclusion: This meta-analysis indicated that increased MPV was associated with severity and mortality in patients with COVID-19. Further research is needed to determine the optimum cut-off point.

19.
The American surgeon ; : 31348221124327, 2022.
Article in English | MEDLINE | ID: covidwho-2009259

ABSTRACT

BACKGROUND: Thomboelastography (TEG) is a point of care viscoelastic test that provides an assessment of clot formation and kinetics. Antiplatelet agents are commonly used but there is limited literature evaluating their possible effects on overall clot kinetics. We aimed to evaluate the relationship between antiplatelet agents and clot kinetics as defined by TEG. METHODS: This is a retrospective study of adult patients who underwent TEG from February 2018 to July 2020. Patients who received anticoagulants or blood transfusions within 72 hours, had an incomplete TEG, were diagnosed with COVID-19, or had liver failure were excluded. Patients were stratified based on antiplatelet status. RESULTS: Of 1060 patients, 119 were included (50 controls, 69 antiplatelet agents-37 aspirin monotherapy, 26 dual antiplatelet therapy). Between the control and antiplatelet therapy groups, there was no significant difference in clot time, maximal clot strength, or fibrinogen level. When compared to control patients, patients on dual antiplatelets had significantly higher fibrinogen levels (408.1 mg/dL vs 481.5 mg/dL, P = .013) but no significant differences in clot time or maximal clot strength. In our subgroup analysis, patients on dual antiplatelets had increased maximal clot strength (58.8° vs 63°, P = .005) and fibrinogen levels (384.1 mg/dL vs 481.5 mg/dL, P = .005) compared to those on aspirin alone. DISCUSSION: Compared to control patients and those on aspirin alone, patients on dual antiplatelets have increased maximal clot strength and increased fibrinogen levels. These results can help physicians better target product resuscitation in patients who are on antiplatelet agents.

20.
American journal of physiology. Lung cellular and molecular physiology ; 2022.
Article in English | MEDLINE | ID: covidwho-2009235

ABSTRACT

INTRODUCTION: E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. An acute vaping model has not been demonstrated in the hamster, which has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration. METHODS: Using a two-day, whole-body vaping exposure protocol in male hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. RESULTS: In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-b), a nicotine-independent increase oxidative stress response (SOD-2), and a nicotine-independent decrease in the vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1b, TNF-a, and CXCL-10), fibrosis (TGF-b and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. CONCLUSION: To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig vaping. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

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