ABSTRACT
BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.
Subject(s)
Antibodies, Viral/blood , Antibody Formation/immunology , COVID-19 Serological Testing , COVID-19/therapy , SARS-CoV-2 , Symptom Assessment , Adult , Aged , Antibodies, Neutralizing/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/physiopathology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Treatment Outcome , United States , COVID-19 SerotherapyABSTRACT
OBJECTIVE: To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM). DESIGN: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450-500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. CONCLUSION: Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.
Subject(s)
Cartilage, Articular/drug effects , Magnesium Chloride/pharmacology , Matrix Metalloproteinase 13/drug effects , Osteoarthritis, Knee/metabolism , Synovial Membrane/drug effects , Synovitis/metabolism , ADAMTS Proteins/drug effects , ADAMTS Proteins/genetics , ADAMTS Proteins/metabolism , Aged , Aggrecans/drug effects , Aggrecans/genetics , Aggrecans/metabolism , Animals , Anterior Cruciate Ligament/surgery , Arthroplasty, Replacement, Knee , Cartilage, Articular/metabolism , Collagen Type II/drug effects , Collagen Type II/genetics , Collagen Type II/metabolism , Disease Models, Animal , Female , Humans , Immunohistochemistry , In Vitro Techniques , Injections, Intra-Articular , Interleukin-1beta/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Meniscectomy , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Real-Time Polymerase Chain Reaction , Synovial Membrane/metabolismABSTRACT
The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.
