ABSTRACT
Importance: Patients with myasthenia gravis (MG) and IST are potentially at increased risk for poor COVID-19 outcome. Objective: To determine whether immunosuppressive therapy (IST) compared to no IST is associated with a higher risk for, first, a symptomatic SARS-CoV-2 infection and, second, a more severe COVID-19 disease course as measured by hospitalization rate and death. Design, setting, and participants: The present study included all available MG patients from the German myasthenia gravis registry, which is a nationwide registry conducted by expert centers since February 2019 (German Clinical Trials Registry DRKS-ID 00024099). Main outcomes and measures: Between May 2020 and June 2021, data were collected on demographics, disease duration, comorbidities, preexistent IST including standard (corticosteroids, azathioprine, mycophenolate mofetil, methotrexate, cyclosporine) and escalation (rituximab, eculizumab) IST, thymectomy, COVID-19 characteristics, and outcomes. COVID-19 was diagnosed with a nasopharyngeal swab by polymerase-chain-reaction. Multiple binary logistic regression models and generalized estimation equation regression models based on matched SARS-CoV-2 infected to non-infected patients were used to estimate the association of IST with SARS-CoV-2 infection. Multiple binary logistic regression models were used to assess the association of IST with outcome of COVID-19 in MG patients. Results: Of 1388 MG patients, 95 (7%) MG patients with a mean age of 58 (SD 18) and median disease duration of 65 months (IQR 27-126) presented with COVID-19. Among them, 39 patients (41%) were male, and 76 (80%) received IST at the time of infection. There were 32 patients (34%) admitted to hospital due to COVID-19, 12 (13%) to the intensive care unit, and a total of 11 patients (12%) died. IST was a risk factor for hospitalization and death in the group of COVID-19 affected MG patients (adjusted odds ratio [OR] 3.04, 95% confi- dence interval [CI] = 1.02-9.06, p=0.046), but not for symptomatic SARS-CoV-2 infection itself in the whole group of MG patients. Conclusions and relevance: In MG patients, preexistent IST was a factor for a severe disease course of COVID-19 but not for the risk for SARS-CoV-2 infection. These data support the consequent implementation of effective strategies to prevent COVID- 19 in this high-risk group.
ABSTRACT
Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19.Hypothesis: Evaluation of a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (<10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response. Results: The CTS detected subtherapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R =0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 94% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%). Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.
ABSTRACT
Background : The COVID-19 pandemic has infected 116 million people to date. Hematologic complications of COVID-19 are common, and associated thrombocytopenia correlates with disease severity. Immune thrombocytopenia (ITP) secondary to COVID-19 has been reported, but the characteristics of this novel entity remain unknown. Aims : To elucidate the demographics, clinical presentations, COVID-19 symptoms, management strategies, complications, and outcomes of patients with ITP secondary to COVID-19. While case series and reviews of ITP secondary to COVID-19 have been published (PMID: 32677007, 32984764), this comprehensive review provides a greater sample size and details regarding management and outcomes. Methods : A comprehensive literature review was performed through 2/28/21 in PubMed and Embase using keywords related to ITP and COVID-19. Articles were excluded based on diagnostic uncertainty, duplication, or irrelevance. Statistical analyses were performed using IBM SPSS Version 27.0. Means and SD reported. Results : Among 106 unique articles identified, 38 were reviewed. Patient demographics and clinical presentations are presented in Table 1. Management and outcomes are described in Table 2. Conclusions : SARS-CoV-2 is a virologic trigger of ITP. Middle-aged adults are most commonly affected, with no gender predilection. Autoimmune disease and cancer are common comorbidities. Mucocutaneous bleeding is the most common presenting symptom. While most patients had COVID-19 symptoms at the time of diagnosis, 12.6% were post-symptomatic and 7.9% never experienced symptoms. Treatment regimens including TPO-RAs were most effective in obtaining a complete response, and steroids may have been more effective than IVIG in the reported population. Treatment complications were rare. Patients with chronic and newly diagnosed ITP had similar presentations and outcomes. Prognostic data were reassuring: the vast majority of patients had complete or partial responses to therapy, and only 1 death was attributable to ITP. Rates of major bleeding were similar to typical ITP. Steroids may be a favorable treatment option given their apparent efficacy for both ITP and COVID-19.