Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
1.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
3.
Curr Rheumatol Rep ; 23(9): 72, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1309082

ABSTRACT

PURPOSE OF THE REVIEW: Elevated levels of anti-phospholipid (aPL) antibodies are the most important criterion in the diagnosis of anti-phospholipid syndrome (APS) and are usually responsible for promoting the risk of thrombotic complications. Now, in the course of the global coronavirus disease 2019 (COVID-19) pandemic, measurable aPL antibodies have also been detected in a noticeable number of patients showing a variety ranging from studies with only isolated positive tests to cohorts with very high positivity. Thus, the question arises as to whether these two different clinical pictures may be linked. RECENT FINDINGS: The ambivalent results showed a frequent occurrence of the investigated aPL antibodies in COVID-19 patients to an individually varying degree. While some question a substantial correlation according to their results, a number of studies raise questions about the significance of a correlation of aPL antibodies in COVID-19 patients. Within the scope of this review, these have now been described and compared with each other. Ultimately, it is necessary to conduct further studies that specifically test aPL antibodies in a larger context in order to make subsequent important statements about the role of APS in COVID-19 and to further strengthen the significance of the described comparisons.


Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , Antibodies, Anticardiolipin/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/immunology , SARS-CoV-2 , beta 2-Glycoprotein I/immunology
4.
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
5.
Front Immunol ; 12: 687534, 2021.
Article in English | MEDLINE | ID: covidwho-1295639

ABSTRACT

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.


Subject(s)
Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/pathology , Bacterial Infections/pathology , COVID-19/pathology , Disseminated Intravascular Coagulation/pathology , Virus Diseases/pathology , Aged , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Bacterial Infections/complications , COVID-19/complications , COVID-19/immunology , Disseminated Intravascular Coagulation/virology , Female , Humans , Male , SARS-CoV-2/immunology , Virus Diseases/complications
6.
Cytokine Growth Factor Rev ; 60: 52-60, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1252646

ABSTRACT

Antiphospholipid antibodies (aPLs), present in 1-5 % of healthy individuals, are associated with the risk of antiphospholipid syndrome (APS), which is the most common form of acquired thrombophilia. APLs may appear following infections or vaccinations and have been reported in patients with COronaVIrus Disease-2019 (COVID-19). However, their association with COVID-19 vaccination is unclear. Notably, a few cases of thrombocytopenia and thrombotic events resembling APS have been reported to develop in recipients of either adenoviral vector- or mRNA-based COVID-19 vaccines. The aim of this review is therefore to speculate on the plausible role of aPLs in the pathogenesis of these rare adverse events. Adenoviral vector-based vaccines can bind platelets and induce their destruction in the reticuloendothelial organs. Liposomal mRNA-based vaccines may instead favour activation of coagulation factors and confer a pro-thrombotic phenotype to endothelial cells and platelets. Furthermore, both formulations may trigger a type I interferon response associated with the generation of aPLs. In turn, aPLs may lead to aberrant activation of the immune response with participation of innate immune cells, cytokines and the complement cascade. NETosis, monocyte recruitment and cytokine release may further support endothelial dysfunction and promote platelet aggregation. These considerations suggest that aPLs may represent a risk factor for thrombotic events following COVID-19 vaccination, and deserve further investigations.


Subject(s)
Antibodies, Antiphospholipid/analysis , Antibodies, Antiphospholipid/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Thrombophilia/etiology , Antiphospholipid Syndrome/etiology , Antiphospholipid Syndrome/immunology , Contraindications, Drug , Humans , Thrombophilia/immunology
7.
J Thromb Thrombolysis ; 52(2): 542-552, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1222780

ABSTRACT

Coronavirus 2019 disease (COVID-19) is associated with coagulation dysfunction that predisposes patients to an increased risk for both arterial (ATE) and venous thromboembolism (VTE) and consequent poor prognosis; in particular, the incidence of ATE and VTE in critically ill COVID-19 patients can reach 5% and 31%, respectively. The mechanism of thrombosis in COVID-19 patients is complex and still not completely clear. Recent literature suggests a link between the presence of antiphospholipid antibodies (aPLs) and thromboembolism in COVID-19 patients. However, it remains uncertain whether aPLs are an epiphenomenon or are involved in the pathogenesis of the disease.


Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Thromboembolism/immunology , Animals , Antibodies, Antiphospholipid/blood , Blood Coagulation , COVID-19/blood , COVID-19/complications , Critical Illness , Humans , Thromboembolism/blood , Thromboembolism/complications , Venous Thromboembolism/blood , Venous Thromboembolism/complications , Venous Thromboembolism/immunology
8.
Ann Rheum Dis ; 80(9): 1236-1240, 2021 09.
Article in English | MEDLINE | ID: covidwho-1203948

ABSTRACT

BACKGROUND: Reports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking. METHODS: 22 COVID-19+ and 20 COVID-19- patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anticardiolipin (aCL), anti-ß2glycoprotien 1 (ß2GP1), antidomain 1 ß2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance was used for continuous variables and Fisher's exact test was used for categorical variables with α=0.05 and the false discovery rate at q=0.05. RESULTS: APLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19+. CONCLUSIONS: Positive APLA serology was associated with more severe disease regardless of COVID-19 status. TRIAL REGISTRATION NUMBER: NCT04747782.


Subject(s)
Antibodies, Anticardiolipin/immunology , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , COVID-19/immunology , Aged , Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , COVID-19/blood , COVID-19/complications , Critical Illness , Female , Humans , Male , Middle Aged , SARS-CoV-2
9.
Curr Rheumatol Rev ; 17(1): 7-16, 2021.
Article in English | MEDLINE | ID: covidwho-1115356

ABSTRACT

Viruses can induce autoimmune diseases, in addition to genetic predisposition and environmental factors. Particularly, coronaviruses are mentioned among the viruses implicated in autoimmunity. Today, the world's greatest threat derives from the pandemic of a new human coronavirus, called "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the responsible agent of coronavirus disease 2019 (COVID-19). First case of COVID-19 was identified in Wuhan, the capital of Hubei, China, in December 2019 and quickly spread around the world. This review focuses on autoimmune manifestations described during COVID-19, including pro-thrombotic state associated with antiphospholipid antibodies (aPL), acute interstitial pneumonia, macrophage activation syndrome, lymphocytopenia, systemic vasculitis, and autoimmune skin lesions. This offers the opportunity to highlight the pathogenetic mechanisms common to COVID-19 and several autoimmune diseases in order to identify new therapeutic targets. In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time. Hence, endothelium might represent the common pathway in which autoimmunity and infection converge. In addition, autoimmune phenomena in COVID-19 can be explained by regulatory T cells impairment and cytokines cascade.


Subject(s)
Autoimmune Diseases/immunology , Autoimmunity/physiology , COVID-19/immunology , Animals , Antibodies, Antiphospholipid/immunology , Antibodies, Antiphospholipid/metabolism , Autoimmune Diseases/etiology , Autoimmune Diseases/metabolism , COVID-19/complications , COVID-19/metabolism , Cytokines/immunology , Cytokines/metabolism , Humans , Inflammation/etiology , Inflammation/immunology , Inflammation/metabolism , Macrophage Activation/physiology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
10.
Transl Res ; 232: 13-36, 2021 06.
Article in English | MEDLINE | ID: covidwho-989350

ABSTRACT

As the world navigates the coronavirus disease 2019 (COVID-19) pandemic, there is a growing need to assess its impact in patients with autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). Patients with SLE are a unique population when considering the risk of contracting COVID-19 and infection outcomes. The use of systemic glucocorticoids and immunosuppressants, and underlying organ damage from SLE are potential susceptibility factors. Most patients with SLE have evidence of high type I interferon activity, which may theoretically act as an antiviral line of defense or contribute to the development of a deleterious hyperinflammatory response in COVID-19. Other immunopathogenic mechanisms of SLE may overlap with those described in COVID-19, thus, studies in SLE could provide some insight into immune responses occurring in severe cases of the viral infection. We reviewed the literature to date on COVID-19 in patients with SLE and provide an in-depth review of current research in the area, including immune pathway activation, epidemiology, clinical features, outcomes, and the psychosocial impact of the pandemic in those with autoimmune disease.


Subject(s)
COVID-19/etiology , Lupus Erythematosus, Systemic/complications , SARS-CoV-2 , Antibodies, Antiphospholipid/immunology , COVID-19/epidemiology , COVID-19/immunology , Complement System Proteins/physiology , Extracellular Traps/physiology , Health Services Accessibility , Humans , Interferon Type I/physiology , Lupus Erythematosus, Systemic/immunology , TOR Serine-Threonine Kinases/physiology
11.
Int J Rheum Dis ; 23(8): 998-1008, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-703587

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease-modifying anti-rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID-19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID-19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID-19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS-CoV-2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID-19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID-19. Rheumatologists need to wait and see whether SARS-CoV-2 infection triggers development of autoimmunity in patients with COVID-19 infection in the long run.


Subject(s)
Autoimmune Diseases/virology , COVID-19/immunology , Antibodies, Antiphospholipid/immunology , Antirheumatic Agents/pharmacology , Antiviral Agents/pharmacology , Autoimmune Diseases/physiopathology , COVID-19/physiopathology , Humans , Hydroxychloroquine/pharmacology , Interferon Type I/immunology , Lupus Erythematosus, Systemic/physiopathology , Rheumatologists , SARS-CoV-2
13.
Rheumatol Int ; 40(10): 1539-1554, 2020 10.
Article in English | MEDLINE | ID: covidwho-646938

ABSTRACT

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.


Subject(s)
Autoimmune Diseases/physiopathology , Coronavirus Infections/physiopathology , Musculoskeletal Diseases/physiopathology , Pneumonia, Viral/physiopathology , Rheumatic Diseases/physiopathology , Antibodies, Antinuclear/immunology , Antibodies, Antiphospholipid/immunology , Antiviral Agents/adverse effects , Arthralgia/etiology , Arthralgia/immunology , Arthralgia/physiopathology , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , Betacoronavirus , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/immunology , Blood Coagulation Disorders/physiopathology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Cross Reactions/immunology , Extracellular Traps/immunology , Fibrin Fibrinogen Degradation Products , Guillain-Barre Syndrome/etiology , Guillain-Barre Syndrome/immunology , Guillain-Barre Syndrome/physiopathology , Humans , Lupus Coagulation Inhibitor/immunology , Molecular Mimicry , Mucocutaneous Lymph Node Syndrome/etiology , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/physiopathology , Muscle Weakness/etiology , Muscle Weakness/immunology , Muscle Weakness/physiopathology , Musculoskeletal Diseases/etiology , Musculoskeletal Diseases/immunology , Myalgia/etiology , Myalgia/immunology , Myalgia/physiopathology , Myocarditis/etiology , Myocarditis/immunology , Myocarditis/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Rheumatic Diseases/etiology , Rheumatic Diseases/immunology , SARS-CoV-2
14.
J Thromb Haemost ; 18(9): 2191-2201, 2020 09.
Article in English | MEDLINE | ID: covidwho-621841

ABSTRACT

BACKGROUND: High incidence of thrombosis in COVID-19 patients indicates a hypercoagulable state. Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest. OBJECTIVES: To illustrate the incidence of criteria (lupus anticoagulant [LAC], anticardiolipin [aCL] immunoglobulin G [IgG]/IgM, antibeta2-glycoprotein I antibodies [aß2GPI] IgG/IgM) and noncriteria (anti-phosphatidyl serine/prothrombin [aPS/PT], aCL, and aß2GPI IgA) aPL in a consecutive cohort of critically ill SARS-CoV-2 patients, their association with thrombosis, antibody profile and titers of aPL. PATIENTS/METHODS: Thirty-one consecutive confirmed COVID-19 patients admitted to the intensive care unit were included. aPL were measured at one time point, with part of the aPL-positive patients retested after 1 month. RESULTS: Sixteen patients were single LAC-positive, two triple-positive, one double-positive, one single aCL, and three aCL IgG and LAC positive. Seven of nine thrombotic patients had at least one aPL. Sixteen of 22 patients without thrombosis were aPL positive, amongst them two triple positives. Nine of 10 retested LAC-positive patients were negative on a second occasion, as well as the double-positive patient. Seven patients were aPS/PT-positive associated to LAC. Three patients were aCL and aß2GPI IgA-positive. CONCLUSION: Our observations support the frequent single LAC positivity during (acute phase) observed in COVID-19 infection; however, not clearly related to thrombotic complications. Triple aPL positivity and high aCL/aß2GPI titers are rare. Repeat testing suggests aPL to be mostly transient. Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID-19 patients.


Subject(s)
Antibodies, Anticardiolipin/immunology , Antibodies, Antiphospholipid/immunology , COVID-19/complications , COVID-19/immunology , Thrombosis/complications , Adult , Aged , Aged, 80 and over , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/immunology , Blood Coagulation , COVID-19/blood , Critical Care , Critical Illness , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Intensive Care Units , Lupus Coagulation Inhibitor/immunology , Male , Middle Aged , Prothrombin/immunology , Thrombosis/blood , Thrombosis/immunology , beta 2-Glycoprotein I/immunology
SELECTION OF CITATIONS
SEARCH DETAIL