Visceral extra-abdominal panniculitis after COVID19.

"Retractile mesenteritis" was the first name given to a rare, benign, inflammatory disease that affects the adipose tissue of the intestinal mesentery and less frequently other locations. Now labeled as mesenteric panniculitis, the pathogenic mechanism remains unclear. Several stimuli could be involved, and it is sometimes associated with other conditions such as malignancy or autoimmune diseases. We present a case of mesenteric panniculitis with extensive abdominal and extra-abdominal involvement that developed a few months after SARS-COV2 infection, raising the hypothesis of this virus as a potential trigger for autoinflammatory and autoimmune diseases.

Rate of Recurrence After Discontinuing Anticoagulation Therapy in Patients With COVID-19-Associated Venous Thromboembolism.

This cohort study assesses the rate of recurrence of venous thromboembolism (VTE) in patients with COVID-19­associated VTE who discontinued anticoagulation therapy.

Evaluation of simple laboratory parameters in SARS-CoV-2 infection: the role of ratios.

BACKGROUND: The real predictive prognostic capacity of cellular indices (or ratios) is unclear in SARS-CoV-2 infection. This study aimed to assess the prognostic role of previously well-known laboratory indices and new ones in hospitalized COVID-19 patients. METHODS: A retrospective observational study from March to May 2022 evaluated laboratory indices on admission (neutrophil to lymphocyte-, derived neutrophil to lymphocyte-, platelet to lymphocyte-, CRP to lymphocyte-, CRP to albumin-, fibrinogen to lymphocyte-, d-dimer to lymphocyte-, ferritin to lymphocyte-, LDH to lymphocyte-, and IL-6 to lymphocyte ratios), in patients hospitalized due to SARS-CoV2 infection to determine the association with mortality, admission to an intensive care unit (ICU), need for non-invasive mechanical ventilation (NIMV), orotracheal intubation (OTI), or combined event at 30 days follow-up. RESULTS: A total of 1113 COVID-19 patients were evaluated with a mean age of 64.1 ± 15.9 years (58.49% male), 166 (14.91%) patients died, 58 (5.21%) required ICU admission, 73 (6.56%) needed NIMV, 46 (4.23%) needed OTI, and 247 (22.19%) presented the combined event. All the ratios evaluated in this study showed statistical significance in the univariate analysis for mortality and combined event; however, only d-dimer to lymphocyte ratio >0.6 presented an independent association in the multivariate analysis for 30-day mortality (adjusted OR 2.32; p = .047) and 30-day combined event (adjusted OR 2.62; p = .014). CONCLUSIONS: Laboratory indices might be a potential biomarker for better prognosis stratification in hospitalized COVID-19 patients. d-Dimer to lymphocyte ratio presents an independent association for 30-day mortality and 30-day adverse outcomes in hospitalized COVID-19 patients.

Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial.

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry.

BACKGROUND: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. METHODS: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. RESULTS: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. CONCLUSIONS: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.

Mid-Regional Pro-Adrenomedullin, Methemoglobin and Carboxyhemoglobin as Prognosis Biomarkers in Critically Ill Patients with COVID-19: An Observational Prospective Study.

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for mortality were 2.40 and 0.46, respectively. The LR+ and LR- for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62-0.81) and 0.72 (95% CI, 0.62-0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding.

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

Bleeding risk in hospitalized patients with COVID-19 receiving intermediate- or therapeutic doses of thromboprophylaxis.

INTRODUCTION: Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID-19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. METHODS: We performed a cohort study of patients hospitalized for COVID-19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. RESULTS: During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate- and 618 (31%) therapeutic-dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non-major bleeding. The 30-day all-cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%-54%) and for non-major bleeding 32% (95% CI: 24%-40%). Multivariable analysis showed increased risk for in-hospital major bleeding associated with D-dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38-3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02-3.95), critical illness (HR, 1.91; 95% CI, 1.14-3.18), and therapeutic-intensity anticoagulation (HR, 1.43; 95% CI, 1.01-1.97). CONCLUSIONS: Among patients hospitalized with COVID-19 receiving intermediate- or therapeutic-intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic-intensity anticoagulation, critical illness, and elevated D-dimer or ferritin levels at admission were associated with increased risk for major bleeding.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

Systematic testing for venous thromboembolism in hospitalized patients with COVID-19 and raised D-dimer levels

Background Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE). Methods We used data from hospitalized patients with COVID-19 that were tested for pulmonary embolism (PE) or deep vein thrombosis (DVT) because of raised D-dimer levels. We aimed to identify patients at increased risk for VTE. Results From March 25 to July 5th 2020, 1,306 hospitalized patients with COVID-19 and raised D-dimer levels underwent testing for VTE in 12 centers. In all, 171 of 714 (24%) had PE, and 161 of 810 (20%) had DVT. The median time elapsed from admission to VTE testing was 12 days, and the median time from D-dimer measurement to testing 2 days. Most patients with VTE were men (62%), mean age was 62±15 years, 45% were in an intensive care unit. Overall, 681 patients (52%) received VTE prophylaxis with standard doses, 241 (18%) with intermediate doses and 100 (7.7%) with therapeutic doses of anticoagulants. On multivariable analysis, patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at increased risk for VTE (odds ratio [OR]: 3.24;95%CI: 2.18-4.83), as were those with a platelet count <100,000/μL (OR: 4.17;95%CI: 1.72-10.0). Conclusions Hospitalized patients with COVID-19 and D-dimer levels >20 times the upper normal range were at an increased risk for VTE. This may help to identify what patients could likely benefit from the use of higher than recommended doses of anticoagulants for VTE prophylaxis.

Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

Immunoserologic Detection and Diagnostic Relevance of Cross-Reactive Autoantibodies in Coronavirus Disease 2019 Patients.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. METHODS: The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. RESULTS: We describe 12 patients positive for the cross-reactive antibody, compared with a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. CONCLUSIONS: Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for autoreactive-mediated complications such as thrombotic or neurologic events.

COVID-19 coagulopathy: An in-depth analysis of the coagulation system.

BACKGROUND: Abnormal coagulation parameters have been reported in COVID-19-infected patients. Although the underlying mechanism of COVID-19 coagulopathy remains unknown, it has been suggested to be a form of disseminated intravascular coagulation (DIC). OBJECTIVES: The aim of our study was to analyze the coagulation parameters of patients with COVID-19, determine whether coagulation factors consumption occurs and identify potential prognostic biomarkers of the disease. PATIENTS/METHODS: Blood samples from hospitalized patients with COVID-19 pneumonia were collected. We performed basic coagulation tests and quantification of coagulation factors and physiological inhibitor proteins. Laboratory data were compared with clinical data and outcomes. RESULTS: The study involved 206 patients (63.6% male). D-dimer was particularly elevated (median 450 ng/mL; IQR 222.5-957.3). Free protein S levels were below the normal range (median 56.6%; IQR: 43.6-68.9), and factor VIII showed an increasing trend (median 173.4%; IQR: 144.1-214.9). However, all coagulation factors were within normal limits. We found no correlation between abnormal coagulation parameters and thrombosis, except for higher D-dimer (HR 1.99; 95% CI 1.3-3.1; P = .002). CONCLUSIONS: COVID-19 is associated with coagulopathy that correlates with poor prognosis. However, we did not demonstrate a consumption of coagulation factors, as seen in DIC.