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1.
Rev Med Virol ; 31(6): e2221, 2021 11.
Article in English | MEDLINE | ID: covidwho-1575100

ABSTRACT

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/antagonists & inhibitors , COVID-19/drug therapy , Complement System Proteins/immunology , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/pathogenicity , ADAM17 Protein/antagonists & inhibitors , ADAM17 Protein/genetics , ADAM17 Protein/immunology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Biomarkers/blood , C-Reactive Protein/genetics , C-Reactive Protein/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Celecoxib/therapeutic use , Complement System Proteins/genetics , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Disease Progression , Doxycycline/therapeutic use , Gene Expression Regulation , Humans , Randomized Controlled Trials as Topic , Severity of Illness Index , Survival Analysis
2.
Front Immunol ; 12: 708101, 2021.
Article in English | MEDLINE | ID: covidwho-1365543

ABSTRACT

Background: Plasma levels of C-reactive protein (CRP), induced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) triggering COVID-19, can rise surprisingly high. The increase of the CRP concentration as well as a certain threshold concentration of CRP are indicative of clinical deterioration to artificial ventilation. In COVID-19, virus-induced lung injury and the subsequent massive onset of inflammation often drives pulmonary fibrosis. Fibrosis of the lung usually proceeds as sequela to a severe course of COVID-19 and its consequences only show months later. CRP-mediated complement- and macrophage activation is suspected to be the main driver of pulmonary fibrosis and subsequent organ failure in COVID-19. Recently, CRP apheresis was introduced to selectively remove CRP from human blood plasma. Case Report: A 53-year-old, SARS-CoV-2 positive, male patient with the risk factor diabetes type 2 was referred with dyspnea, fever and fulminant increase of CRP. The patient's lungs already showed a pattern enhancement as an early sign of incipient pneumonia. The oxygen saturation of the blood was ≤ 89%. CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started immediately. CRP apheresis was performed via peripheral venous access on 4 successive days. CRP concentrations before CRP apheresis ranged from 47 to 133 mg/l. The removal of CRP was very effective with up to 79% depletion within one apheresis session and 1.2 to 2.14 plasma volumes were processed in each session. No apheresis-associated side effects were observed. It was at no point necessary to transfer the patient to the Intensive Care Unit or to intubate him due to respiratory failure. 10 days after the first positive SARS-CoV-2 test, CRP levels stayed below 20 mg/l and the patient no longer exhibited fever. Fourteen days after the first positive SARS-CoV-2 test, the lungs showed no sign of pneumonia on X-ray. Conclusion: This is the first report on CRP apheresis in an early COVID-19 patient with fulminant CRP increase. Despite a poor prognosis due to his diabetes and biomarker profile, the patient was not ventilated, and the onset of pneumonia was reverted.


Subject(s)
Blood Component Removal/methods , C-Reactive Protein/metabolism , COVID-19/therapy , Respiratory Insufficiency/prevention & control , C-Reactive Protein/analysis , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/complications , COVID-19/immunology , Humans , Lung/diagnostic imaging , Lung/immunology , Male , Middle Aged , Respiratory Insufficiency/immunology , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Treatment Outcome
3.
Signal Transduct Target Ther ; 6(1): 289, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1333903

ABSTRACT

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.


Subject(s)
Adaptive Immunity , COVID-19/immunology , Immunity, Innate , Lymphocytes/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , C-Reactive Protein/immunology , Female , Humans , Interleukin-6/immunology , Pregnancy , Retrospective Studies , Sequence Analysis, RNA , Single-Cell Analysis
4.
Viruses ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1314765

ABSTRACT

Distinguishing between severe and nonsevere COVID-19 to ensure adequate healthcare quality and efficiency is a challenge for the healthcare system. The aim of this study was to assess the usefulness of CBC parameters together with analysis of FLC serum concentration in risk stratification of COVID-19. MATERIALS AND METHODS: CBC was analyzed in 735 COVID ICU, COVID non-ICU, and non-COVID ICU cases. FLC concentration was analyzed in 133 of them. RESULTS: COVID ICU had neutrophils and lymphocytes with the greatest size, granularity, and nucleic acid content. Significant differences in concentrations of κ and λ FLCs were shown between COVID ICU and COVID non-ICU. However, no difference was found in the κ/λ ratio between these groups, and the ratio stayed within the reference value, which indicates the presence of polyclonal FLCs. FLC κ measurement has significant power to distinguish between severe COVID-19 and nonsevere COVID-19 (AUC = 0.7669), with a sensitivity of 86.67% and specificity of 93.33%. The κ coefficients' odds ratio of 3.0401 was estimated. CONCLUSION: It can be concluded that the results obtained from the measure of free light immunoglobulin concentration in serum are useful in distinguishing between severe and nonsevere COVID-19.


Subject(s)
COVID-19/immunology , Immunoglobulin Light Chains/blood , SARS-CoV-2/immunology , Aged , Aged, 80 and over , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19 Serological Testing , Female , Ferritins/immunology , Humans , Immunoglobulin Light Chains/immunology , Intensive Care Units , Interleukin-6/immunology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index
5.
J Virol Methods ; 296: 114224, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294028

ABSTRACT

INTRODUCTION: We evaluated the Roche Elecsys IL6 assay on the Cobas immunoassay analyser. METHOD: Serum IL6 of 144 controls were compared to 52 samples from patients with COVID-like respiratory symptoms (17 SARS-CoV-2 RT-PCR positive); 25 of these were from the intensive care unit (ICU). We compared the IL6 levels to C-reactive protein (CRP) and procalcitonin (PCT) levels in all cases. RESULTS: The IL6 assay had coefficient-of-variation (CV) of 2.3 % (34.1 pg/mL) and 2.5 % (222.5 pg/mL), a limit of quantitation <1.6 pg/mL, and was linear from 1.6 to 4948 pg/mL. There was a significant difference in IL6 values between patients with COVID-like respiratory symptoms versus controls (p < 0.001). ROC analysis showed that IL6 > 6.4 pg/mL identified symptomatic cases (AUC 0.94, sensitivity 88.2 %, specificity 97.2 %). There was a significant difference between the IL6 of symptomatic ICU/non-ICU cases (median IL6 228 vs 11 pg/mL, p < 0.0001); ROC analysis showed IL6 > 75 pg/mL (sensitivity 76.0 %, specificity 88.9 %) was superior to CRP and PCT in predicting ICU admission (AUC: IL6 0.83, CRP 0.71, PCT 0.82). CONCLUSION: The performance of Elecsys IL6 assay is in keeping with the manufacturer's claims. IL6 > 6.4 pg/mL differentiates healthy from suspected COVID-19 cases and appears to be raised earlier than the other inflammatory markers in some cases. IL6 > 75 pg/mL was a good predictor of ICU admission.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/immunology , Interleukin-6/immunology , SARS-CoV-2/immunology , Biomarkers/blood , C-Reactive Protein/immunology , Female , Humans , Immunoassay , Immunologic Tests , Intensive Care Units , Interleukin-6/blood , Male , Procalcitonin/blood , Procalcitonin/immunology , ROC Curve , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
6.
Curr Rheumatol Rep ; 23(8): 65, 2021 07 03.
Article in English | MEDLINE | ID: covidwho-1293441

ABSTRACT

PURPOSE OF REVIEW: COVID-19 patients have a procoagulant state with a high prevalence of thrombotic events. The hypothesis of an involvement of antiphospholipid antibodies (aPL) has been suggested by several reports. Here, we reviewed 48 studies investigating aPL in COVID-19 patients. RECENT FINDINGS: Prevalence of Lupus Anticoagulant (LA) ranged from 35% to 92% in ICU patients. Anti-cardiolipin (aCL) IgG and IgM were found in up to 52% and up to 40% of patients respectively. Anti-ß2-glycoprotein I (aß2-GPI) IgG and IgM were found in up to 39% and up to 34% of patients respectively. Between 1% and 12% of patients had a triple positive aPL profile. There was a high prevalence of aß2-GPI and aCL IgA isotype. Two cohort studies found few persistent LA but more persistent solid phase assay aPL over time. aPL determination and their potential role is a real challenge for the treatment of this disease.


Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , Thrombosis/immunology , Antibodies, Anticardiolipin/immunology , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/complications , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/immunology , SARS-CoV-2 , Severity of Illness Index , Thrombosis/blood , Thrombosis/etiology , beta 2-Glycoprotein I/immunology
7.
Sci Rep ; 11(1): 13350, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281743

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we have assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with COVID-19 and we have correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 62 (27.3%) pregnant women and 165 (72.7%) postpartum women, 21 (9.2%) patients received oxygen supplementation and 2 (0.9%) required admission to intensive care unit but none died. During hospitalization leukocytes (p < 0.001), neutrophils (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001) and C reactive protein (p < 0.001) decreased significantly, whereas lymphocytes (p < 0.001), platelets (p < 0.001) and ferritin (p = 0.001) increased. Lymphocyte values at admission were correlated with oxygen need, with a 26% higher risk of oxygen supplementation for each 1000 cells decreases. Overall, in obstetric patients hospitalized with COVID-19, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced lymphocyte values at admission.


Subject(s)
C-Reactive Protein/immunology , COVID-19 , Fibrin Fibrinogen Degradation Products/immunology , Lymphocytes , Adult , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , Female , Humans , Lymphocytes/cytology , Lymphocytes/immunology , Pregnancy , Retrospective Studies
8.
PLoS One ; 16(6): e0252818, 2021.
Article in English | MEDLINE | ID: covidwho-1264219

ABSTRACT

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.


Subject(s)
COVID-19/blood , Inflammation/blood , Adult , Age Factors , Aged , Aging , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , C-Reactive Protein/analysis , C-Reactive Protein/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , Female , Ferritins/blood , Ferritins/immunology , Hospitalization , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Inflammation/diagnosis , Inflammation/epidemiology , Inflammation/immunology , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
9.
Cells ; 10(5)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1234671

ABSTRACT

Macrophages play a key role in induction of inflammatory responses. These inflammatory responses are mostly considered to be instigated by activation of pattern recognition receptors (PRRs) or cytokine receptors. However, recently it has become clear that also antibodies and pentraxins, which can both activate Fc receptors (FcRs), induce very powerful inflammatory responses by macrophages that can even be an order of magnitude greater than PRRs. While the physiological function of this antibody-dependent inflammation (ADI) is to counteract infections, undesired activation or over-activation of this mechanism will lead to pathology, as observed in a variety of disorders, including viral infections such as COVID-19, chronic inflammatory disorders such as Crohn's disease, and autoimmune diseases such as rheumatoid arthritis. In this review we discuss how physiological ADI provides host defense by inducing pathogen-specific immunity, and how erroneous activation of this mechanism leads to pathology. Moreover, we will provide an overview of the currently known signaling and metabolic pathways that underlie ADI, and how these can be targeted to counteract pathological inflammation.


Subject(s)
Antibodies/metabolism , C-Reactive Protein/metabolism , Inflammation/immunology , Serum Amyloid P-Component/metabolism , Antibodies/immunology , C-Reactive Protein/immunology , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Inflammation/metabolism , Inflammation/microbiology , Macrophages/immunology , Macrophages/metabolism , Metabolic Networks and Pathways/immunology , Receptors, Fc/metabolism , Serum Amyloid P-Component/immunology , Signal Transduction/immunology
11.
Trials ; 22(1): 246, 2021 Apr 02.
Article in English | MEDLINE | ID: covidwho-1166928

ABSTRACT

OBJECTIVES: This study is conducted to investigate efficacy of pomegranate juice on inflammatory biomarkers, C-reactive protein (CRP), interleukin 6(IL-6), erythrocyte sedimentation rate (ESR) and complete blood count (CBC) in hospitalized patients with mild to moderate coronavirus disease 2019 (COVID- 19). TRIAL DESIGN: This is a randomized, placebo-controlled, double-blind, parallel 2-arm (1:1 ratio) clinical trial. PARTICIPANTS: Patients with COVID-19 admitted to hospitals in Yasuj City, Kohgiluyeh and Boyer-Ahmad Province, Iran. INCLUSION CRITERIA: Informed consent Patients 18 years of age or older Diagnosis of COVID-19 based on real-time polymerase chain reaction (RT-PCR) test EXCLUSION CRITERIA: Pregnancy or lactation Immunoglobulin A (IgA) level <61 mg/dl Disseminated intravascular coagulation or any other types of coagulopathy Severe congestive heart failure Participation in any clinical trial within 30 days prior to enrollment in this RCT Other contraindications determined by the specialist. INTERVENTION AND COMPARATOR: Intervention: 500 ml pomegranate juice and standard of care hospital treatment for COVID-19 Comparator: matching placebo containing 500 ml of red water and standard of care hospital treatment for COVID-19 Both intervention and comparator to be taken twice a day, after lunch and dinner, for 14 days. CRITERIA FOR DISCONTINUING: Transfer of patients to intensive care unit (ICU) Death Unwillingness to continue participating in the study MAIN OUTCOMES: The main outcomes of this study are levels of inflammatory biomarkers, CRP, IL-6, ESR, and CBC after 14 days of treatment. RANDOMIZATION: Eligible patients will be randomly assigned into the intervention or control group in a 1:1 ratio. Randomization will be performed based on 8 permuted blocks with block sizes of 6 and they will be stratified according to sex and age categories. Randomization sequences will be prepared by the trial's pharmacist using computer-generated random numbers. BLINDING (MASKING): This study is a double-blind clinical trial (participant, researcher). The pomegranate juice and placebo juice are packaged in identical bottles, and the researcher and all the patients will be unaware of the study assignment until the end of the study. To ensure blinding, the randomization sequences will be kept in identical, opaque, sealed, and sequentially numbered envelopes. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The calculated total sample size is 48 patients, with 24 patients assigned into each group. TRIAL STATUS: The protocol is Version 1.0, on March 3, 2021. Recruitment started on February 28, 2021, and is anticipated to be completed by May 21, 2021. TRIAL REGISTRATION: The Name of registering trial Effects of Pomegranate Juice (Punica Granatum) on Inflammatory Biomarkers and CBC in Patients with COVID-19: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Iranian registry of clinical trials (IRCT) Registration Number: IRCT20150711023153N2 Date of Trial Registration February 28, 2021, retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials҆ website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Fruit and Vegetable Juices , Pomegranate , Randomized Controlled Trials as Topic , Blood Cell Count , Blood Sedimentation , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/immunology , Double-Blind Method , Hospitalization , Humans , Interleukin-6/immunology , SARS-CoV-2
12.
RMD Open ; 7(1)2021 03.
Article in English | MEDLINE | ID: covidwho-1166567

ABSTRACT

BACKGROUND: The CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality. PATIENTS AND METHODS: The first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects). RESULTS: The natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90. CONCLUSION: Causal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , C-Reactive Protein/immunology , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Methylprednisolone/therapeutic use , COVID-19/immunology , Causality , Cytokine Release Syndrome/immunology , Historically Controlled Study , Humans , Inflammation/immunology , Mediation Analysis , Mortality , SARS-CoV-2 , Survival Rate , Treatment Outcome
13.
Aging (Albany NY) ; 13(5): 6289-6297, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1134590

ABSTRACT

OBJECTIVES: To retrospectively evaluate the clinical and immunological characteristics of patients who died of COVID-19 and to identify patients at high risk of death at an early stage and reduce their mortality. RESULTS: Total white blood cell count, neutrophil count and C-reactive protein were significantly higher in patients who died of COVID-19 than those who recovered from it (p < 0.05), but the total lymphocyte count, CD4 + T cells, CD8 + T cells, B cells and natural killer cells were significantly lower when compared in the same groups. Multiple logistic regression analysis showed that increased D-dimer, decreased CD4 + T cells and increased neutrophils were risk factors for mortality. Further multiple COX regression demonstrated that neutrophil ≥ 5.27 × 109/L increased the risk of death in COVID-19 patients after adjustment for age and gender. However, CD4 + T cells ≥ 260/µL appeared to reduce the risk of death. CONCLUSION: SARS-CoV-2 infection led to a significant decrease of lymphocytes, and decreased CD4 + T cell count was a risk factor for COVID-19 patients to develop severe disease and death. METHODS: This study included 190 hospitalized COVID-19 patients from January 30, 2020 to March 4, 2020 in Wuhan, China, of whom 85 died and 105 recovered. Two researchers independently collected the clinical and laboratory data from electronic medical records.


Subject(s)
COVID-19/blood , COVID-19/immunology , Lymphocytes/immunology , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , C-Reactive Protein/analysis , C-Reactive Protein/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/diagnosis , COVID-19/mortality , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Humans , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , Neutrophils/immunology , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
14.
Front Immunol ; 12: 630430, 2021.
Article in English | MEDLINE | ID: covidwho-1120200

ABSTRACT

C-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.


Subject(s)
C-Reactive Protein/immunology , COVID-19/immunology , Myocardial Infarction/immunology , SARS-CoV-2/immunology , Stroke/immunology , Animals , Cell Death/immunology , Cell Hypoxia/immunology , Complement C4/immunology , Humans , Rabbits
15.
Eur J Endocrinol ; 184(5): 699-709, 2021 May.
Article in English | MEDLINE | ID: covidwho-1122229

ABSTRACT

Objective: Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. Methods: We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3-7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. Results: The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. Conclusions: Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.


Subject(s)
COVID-19/blood , Thyroglobulin/blood , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood , Adult , Aged , Aged, 80 and over , Autoantibodies/immunology , C-Reactive Protein/immunology , COVID-19/immunology , Female , Humans , Hydrocortisone/blood , Interleukin-6/immunology , Male , Middle Aged , SARS-CoV-2 , Thyroglobulin/immunology , Thyroid Function Tests
16.
PLoS One ; 16(2): e0247605, 2021.
Article in English | MEDLINE | ID: covidwho-1105820

ABSTRACT

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles. In addition, histone H4 markedly potentiates IAV induced neutrophil respiratory burst responses. Prior studies have shown reactive oxidants to be detrimental during severe IAV infection. C reactive protein (CRP) and surfactant protein D (SP-D) rise during IAV infection. We now show that both of these innate immune proteins bind to histone H4 and significantly down regulate respiratory burst and other responses to histone H4. Isolated constructs composed only of the neck and carbohydrate recognition domain of SP-D also bind to histone H4 and partially limit neutrophil responses to it. These studies indicate that complexes formed of histones and IAV are a potent neutrophil activating stimulus. This finding could account for excess inflammation during IAV or other severe viral infections. The ability of CRP and SP-D to bind to histone H4 may be part of a protective response against excessive inflammation in vivo.


Subject(s)
C-Reactive Protein/immunology , Histones/immunology , Influenza A virus/immunology , Influenza, Human/immunology , Neutrophils/immunology , Pulmonary Surfactant-Associated Protein D/immunology , Cells, Cultured , Humans , Immunity, Innate , Inflammation/etiology , Inflammation/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza, Human/complications
17.
Seizure ; 84: 66-68, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065590

ABSTRACT

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.


Subject(s)
Brain Diseases/physiopathology , COVID-19/physiopathology , De Lange Syndrome/complications , Epilepsy/physiopathology , Seizures/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , Acute Kidney Injury/etiology , Adolescent , Airway Extubation , Anticonvulsants/therapeutic use , Blood Coagulation Disorders/etiology , Bone Marrow Failure Disorders , Brain Diseases/diagnostic imaging , Brain Diseases/etiology , Brain Diseases/pathology , Brain Edema/diagnostic imaging , Brain Edema/etiology , C-Reactive Protein/immunology , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Disease Progression , Electroencephalography , Epilepsy/complications , Epilepsy/drug therapy , Female , Ferritins/metabolism , Humans , Influenza B virus , Influenza, Human/complications , Levetiracetam/therapeutic use , Magnetic Resonance Imaging , Midazolam/therapeutic use , Necrosis , Phenobarbital/therapeutic use , Pseudomonas Infections/complications , Respiration, Artificial , Rhabdomyolysis/complications , Rhabdomyolysis/etiology , SARS-CoV-2 , Seizures/drug therapy , Seizures/etiology , Sepsis/etiology , Sepsis/physiopathology , Sepsis/therapy , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/therapy , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/therapy
18.
Blood Rev ; 45: 100707, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064893

ABSTRACT

A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a "Cytokine Storm Syndrome" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.


Subject(s)
COVID-19/immunology , Castleman Disease/immunology , Cytokine Release Syndrome/immunology , Immunologic Factors/therapeutic use , Lymphohistiocytosis, Hemophagocytic/immunology , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal/therapeutic use , Biomarkers/blood , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Castleman Disease/drug therapy , Castleman Disease/pathology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Ferritins/blood , Ferritins/immunology , Gene Expression Regulation , Humans , Immunotherapy, Adoptive/adverse effects , Interleukin-1/antagonists & inhibitors , Interleukin-1/blood , Interleukin-1/immunology , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Interleukin-6/immunology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/pathology , Signal Transduction
19.
Int J Infect Dis ; 102: 303-309, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060009

ABSTRACT

INTRODUCTION: Tocilizumab (TCZ) is an interleukin-6 receptor antagonist, which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), which aims to ameliorate the cytokine release syndrome (CRS) induced acute respiratory distress syndrome (ARDS). However, there are no consistent data about who might benefit most from it. METHODS: We administered TCZ on a compassionate-use basis to patients with SSP who were hospitalized (excluding intensive care and intubated cases) and who required oxygen support to have a saturation >93%. The primary endpoint was intubation or death after 24 h of its administration. Patients received at least one dose of 400 mg intravenous TCZ from March 8, 2020 to April 20, 2020. RESULTS: A total of 207 patients were studied and 186 analyzed. The mean age was 65 years and 68% were male patients. A coexisting condition was present in 68% of cases. Prognostic factors of death were older age, higher IL-6, d-dimer and high-sensitivity C-reactive protein (HSCRP), lower total lymphocytes, and severe disease that requires additional oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p < 0·001) in those receiving the drug when the oxygen support was high (FiO2 >0.5%). CONCLUSIONS: TCZ is well tolerated in patients with SSP, but it has a limited effect on the evolution of cases with high oxygen support needs.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , Adult , Aged , Aged, 80 and over , C-Reactive Protein/immunology , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Compassionate Use Trials , Critical Care/statistics & numerical data , Female , Humans , Immunologic Factors , Interleukin-6/immunology , Male , Middle Aged , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Spain
20.
J Nanobiotechnology ; 18(1): 130, 2020 Sep 10.
Article in English | MEDLINE | ID: covidwho-755216

ABSTRACT

Fast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets-the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.


Subject(s)
Biomarkers/analysis , C-Reactive Protein/analysis , Immunoassay/methods , Interleukin-6/analysis , Quantum Dots/chemistry , Sepsis/diagnosis , Antibodies/immunology , Betacoronavirus/isolation & purification , C-Reactive Protein/immunology , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Interleukin-6/immunology , Limit of Detection , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Point-of-Care Systems , SARS-CoV-2 , Sepsis/metabolism , Software , Ultraviolet Rays
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