Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis
Clinical reviews in allergy & immunology. 2022;:1-33
Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4(+) T/CD8(+) T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3(+) T,CD4(+)T and CD8(+)T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4(+) and CD8(+) T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.
Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment
Evidence-based complementary and alternative medicine : eCAM. 2021;2021:5513744
PURPOSE Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.
Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis
Arthritis research & therapy. 2021;23(1):57
BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. METHODS Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. RESULTS Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I(2) = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I(2) = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I(2) = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I(2) = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I(2) = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I(2) = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I(2) = 75.5%). CONCLUSIONS Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.
What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis
Rheumatology (Oxford). 2020
OBJECTIVE The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease. METHODS Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1. RESULTS Eight retrospective cohort studies, characterizing 12 176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) -0.30; 95% CI: -0.58, -0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: -0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups. CONCLUSION Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.
A clinical analysis of treatment with recombinant human thrombopoietin combined with large doses of dexamethasone in primary immune thrombocytopenia
Zhonghua Nei Ke Za Zhi. 2016;55((3)):202-5.
OBJECTIVE To study the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with dexamethasone as front line regimen in patients with primary immune thrombocytopenia (ITP). METHODS This study was a prospective, randomized, controlled trial. A total of 59 primary ITP patients were enrolled at the First Affiliated Hospital, Xinjiang Medical University from June 2013 to February 2015. All subjects were randomized into study group (30 cases) and control group (29 cases). The study group was scheduled to receive high-dose dexamethasone (40 mg intravenously d1-4) combined with rhTPO (300 U.kg(-1).d(-1) subcutaneously d1-14). Once absolute platelet count reached >50x10(9)/L, rhTPO stopped. Patients in control group were just administrated with high-dose dexamethasone (40 mg intravenously d1-4). Efficacy and adverse reactions were evaluated. RESULTS The short-term (15 days) and mid-term (3 months) response rates in the study group were 83.3%(25/30) and 76.7%(23/30) respectively, which were both significantly better than those in the control group [51.7%(15/29) and 20.7%(6/29) respectively] (P<0.01). In the study group and control group, the median time platelet count reached 100x10(9)/L was 6.0 and 6.8 days respectively. In the study group, the time of TPO usage was (6.1+/-1.7) days. The incidence of adverse reactions in both groups was comparable and slight. The most common TPO related adverse events included knee ache and fatigue, which accounted for 6.7% (2/30) in the study group. CONCLUSIONS Recombinant human TPO combined with dexamethasone as front line treatment for primary ITP shows significant advantages in both short-term and mid-term responses with less and manageable adverse reactions. This may provide a new method to treat patients with primary ITP.
Systematic review and network meta-analysis of upper gastrointestinal hemorrhage interventions
Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2016;39((6)):2477-2491.
BACKGROUND/AIMS: Upper gastrointestinal hemorrhage (UGH) is a serious medical condition which affects a large number of individuals. Endoscopic therapy accompanied by medication is a standard approach that is used to improve the prognosis of UGH patients and a few medications have been developed including proton pump inhibitors (PPIs), histamine H2 receptor antagonist (H2RA), somatostatin analogues and tranexamic acid. This study is set to compare the efficacy and safety of various medical interventions that are used to manage upper gastrointestinal bleeding. METHODS We searched PubMed, Cochrane Library, and Embase for relevant articles. Eligible studies were determined by using both the inclusion and exclusion criteria. Both traditional pair-wise meta-analysis and net-work analysis were carried out to evaluate the corresponding interventions. RESULTS AND CONCLUSION PPI is an effective medication for UGH patients and intravenous PPI exhibits equivalent effectiveness and safety in comparison to oral PPI. H2RA is not recommended for UGH patients as patients treated with H2RA are associated with an increased risk of adverse events including rebleeding, need for surgery and all-cause mortality. Moreover, patients treated with H2RA exhibit an increased length of average hospital stay and blood transfusion amount compared to those treated with PPI. Tranexamic acid is also considered as another promising medication for UGH.
Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study
Journal of Viral Hepatitis. 2006;13((9):):597-604.
To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0. 05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.