Immunoprofiling of cytokines, chemokines, and growth factors in female patients with systemic lupus erythematosus- a pilot study.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease affecting different organ systems. This study aimed to determine the concentrations of 30 different human cytokines, chemokines, and growth factors in human plasma to understand the role of these markers in the pathogenicity of SLE using Luminex Multiple Analyte Profiling (xMAP) technology. Plasma samples were obtained from patients with SLE (n = 28), osteoarthritis (OA) (n = 9), and healthy individuals (n = 12) were obtained. High levels of TNF, IL-6, IFN-γ, INF-α, IL-4, IL-5, IL-13, IL-8, IP-10, MIG, MCP-1, MIP-1ß, GM-CSF, G-CSF, EGF, VEGF, IL-12, IL-1RA, and IL-10 was detected in SLE patients compared with the OA and healthy control groups. xMAP analysis has been used to address the differential regulation of clinical heterogeneity and immunological phenotypes in SLE patients. In addition, complete disease phenotyping information along with cytokine immune profiles would be useful for developing personalized treatments for patients with SLE.

Deciphering SARS CoV-2-associated pathways from RNA sequencing data of COVID-19-infected A549 cells and potential therapeutics using in silico methods.

BACKGROUND: Coronavirus (CoV) disease (COVID-19) identified in Wuhan, China, in 2019, is mainly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and is caused by SARS CoV-2, which belongs to the Coronaviridae family. Determining the underlying disease mechanisms is central to the identification and development of COVID-19-specific drugs for effective treatment and prevention of human-to-human transmission, disease complications, and deaths. METHODS: Here, next-generation RNA sequencing (RNA Seq) data were obtained using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells from the Gene Expression Omnibus (GEO) (GSE147507), and quality control (QC) was assessed before RNA Seq analysis using CLC Genomics Workbench 20.0. Differentially expressed genes (DEGs) were imported into BioJupies to decipher COVID-19 induced signaling pathways and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID -19 specific gene signatures. In addition, iPathwayGuide was used to identify COVID-19-specific signaling pathways, as well as drugs and natural products with anti-COVID-19 potential. RESULTS: Here, we identified the potential activation of upstream regulators such as signal transducer and activator of transcription 2 (STAT2), interferon regulatory factor 9 (IRF9), and interferon beta (IFNß), interleukin-1 beta (IL-1ß), and interferon regulatory factor 3 (IRF3). COVID-19 infection activated key infectious disease-specific immune-related signaling pathways such as influenza A, viral protein interaction with cytokine and cytokine receptors, measles, Epstein-Barr virus infection, and IL-17 signaling pathway. Besides, we identified drugs such as prednisolone, methylprednisolone, diclofenac, compound JQ1, and natural products such as Withaferin-A and JinFuKang as candidates for further experimental validation of COVID-19 therapy. CONCLUSIONS: In conclusion, we have used the in silico next-generation knowledge discovery (NGKD) methods to discover COVID-19-associated pathways and specific therapeutics that have the potential to ameliorate the disease pathologies associated with COVID-19.

Immunogenicity of The BNT162b2 COVID-19 mRNA and ChAdOx1 nCoV-19 Vaccines in Patients with Hemoglobinopathies.

INTRODUCTION: Studies assessing immune responses following Pfizer-BioNTech BNT162b2 mRNA COVID-19 (Pfizer) and ChAdOx1 nCoV-19 AZD1222 (AstraZeneca) vaccines in patients with hemoglobinopathy are non-existent in the literature despite being thought at high risk of infection. METHODS: Prospectively, we collected serum from patients with hemoglobinopathies at least 14 days post vaccine and measured neutralizing antibodies (nAb) in addition to binding antibodies using in-house assays. RESULTS: All 66 participants mounted a significant binding antibody response (100%), but nAbs were detected in (56/66) post-vaccine with a rate of 84.5%. Age, gender, vaccine type, spleen status, hydroxyurea use, and hyperferritinemia did not affect the rate significantly. While 23/32 (71.8%) patients receiving only one dose of the vaccine were able to mount a positive response, 33/34 (97.05%) of those who had two doses of any vaccine type had a significant nAbs response. Patients who had anti-nucleocapsid (N), signifying asymptomatic infection in the past, were able to produce nAbs (31/31). No nAbs were detected in 10/35 (28.5%) patients with no anti-N antibodies. CONCLUSION: Our results provide supportive data when advising patients with hemoglobinopathy to receive COVID-19 vaccines and ensure booster doses are available for better immunity. Whenever available, measurement of nAb is recommended.

Implications of SARS-CoV-2 infection on the clinical, hematological, and inflammatory parameters in COVID-19 patients: A retrospective cross-sectional study.

BACKGROUND: The current coronavirus pandemic (COVID-19) was caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2). COVID-19 is characterized by atypical pneumonia, mild colds, and more severe illnesses, such as severe acute respiratory distress, thrombosis, organ failure, and various secondary bacterial and fungal infections. Notably, the severity of COVID-19 in different age groups is not well known, and the validity of clinical laboratory data remains unclear. METHODS: In this retrospective cross-sectional study, we examined differential regulation of clinical, hematologic, and inflammatory biomarkers in COVID-19 patients. We divided 104 COVID-19 patients into five different groups according to age (0-17, 18-45, 46-65, 66-79, and >80 years). Baseline data (sex, comorbidities, intensive care admission, and medications), hematologic markers, liver, and renal function tests, coagulation, and inflammatory markers were examined in these groups. Receiver operator characteristic (ROC) analysis was used to determine the optimal threshold for predicting COVID-19 biological markers. RESULTS: We found that the highest percentage (45%) of COVID-19 patients was in the age group of 46-65 years. The hematologic parameters (WBC, HB, and PLT) were normal between the patient groups. The area under the curve in ROC analysis showed significant differences in the levels of creatine, GGT, BUN, CRP, D-dimer, ferritin, AST, and procalcitonin between the patients of age groups 46-65 and 66-79 years. Renal biomarkers were significantly high in most patients, regardless of age. In contrast, the liver biomarkers, did not differ significantly between patient groups. CONCLUSION: The main finding of our study is that laboratory parameters such as GGT, creatinine, BUN, CRP, procalcitonin, ferritin and D-dimer were differentially regulated in COVID -19 patients of different age groups. Importantly, these laboratory parameters may help as clinical predictors to assess the severity of the disease in the population. We conclude here that age is an important factor influencing COVID-19 severity.

Low clinical utility of testing for anti-platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV-19 vaccine.

INTRODUCTION: The development of anti-platelet factor 4 (PF4) antibodies is linked to a rare thrombotic complication described now as vaccine-induced immune thrombotic thrombocytopenia (VITT). This clinical syndrome with thrombosis and thrombocytopenia was reported after exposure to the Oxford-AstraZeneca COVID-19 vaccine, ChAdOx1 nCoV-19 vaccine (AZD1222), and Ad26.COV2.S vaccine (Janssen/Johnson & Johnson). In the absence of the clinical features, the incidence of positive anti-PF4 antibodies in asymptomatic individuals post-vaccination is unclear. METHODS: The aim of this study was to evaluate the development of anti-PF4 antibodies in asymptomatic individuals 14-21 days after receiving the first dose of ChAdOx1 nCoV-19 vaccine (AZD1222) and BNT162b2 vaccine. Prospectively, we collected serum from individuals before and after ChAdOx1 nCoV-19 vaccine and BNT162b2 vaccine and measured anti-PF4 antibodies using the Asserachrom HPIA IgG ELISA (Stago, Asnieres, France). RESULTS: We detected positive anti-PF4 antibodies in 5 of 94 asymptomatic individuals post-vaccine with a rate of 5.3% with low titers (OD 0.3-0.7). Four of 5 individuals who tested positive after the vaccine had also positive anti-PF4 antibodies before the vaccine, which indicates that a majority of the positive results are due to preexisting anti-PF4 antibodies. We did not find a relation between the development of anti-PF4 antibodies and the immune response to the vaccine, status of prior COVID-19 infection, and baseline characteristics of participants. None of the participants developed thrombosis nor thrombocytopenia. CONCLUSION: Our results provide new evidence to guide the diagnostic algorithm of suspected cases of VITT. In the absence of thrombosis and thrombocytopenia, there is a low utility of testing for anti-PF4 antibodies.