A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial.

OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN: Randomised controlled, adaptive, open label clinical trial. SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.

Bullous pemphigoid after second dose of mRNA- (Pfizer-BioNTech) Covid-19 vaccine: A case report.

INTRODUCTION AND IMPORTANCE: Messenger RNA vaccines, commonly known as mRNA vaccines, are the first COVID-19 vaccines that have been authorized and licensed in the United States. Two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) are available. Mass vaccination remains the most critical way to halt the spread of the COVID pandemic. The most common adverse effects of the COVID vaccines are headache, muscular soreness, weariness, redness, swelling, and tenderness at the injection site. The dermatological adverse effects of mRNA vaccines, on the other hand, are little understood. We present a case of bullous fixed medication eruption following delivery of the second dose of Pfizer's Covid-19 vaccination. CASE PRESENTATION: We discuss the case of a 78-year-old man who went to the Emergency Department at King Fahad Medical City in Riyadh, Saudi Arabia, with numerous bullae throughout his extremities one day after receiving the second dosage of Pfizer Covid-19 vaccine. The bullae began three days before his presentation, and they were preceded by intense pruritus and urticated plaques. A skin biopsy was performed which revealed IgG (+1), IgM (+1), and C3 (+1) staining of the basement membrane. Another punch skin biopsy taken from an intact bulla was suboptimal compressing of dermal tissue only, revealing modest perivascular lymphocytic infiltrative and scattered eosinophils. This pathological picture with superficial perivascular inflammatory dermatitis, and the presence of eosinophils suggests drug-induced bullous pemphigoid. The patient was treated with topical and systemic corticosteroids, fusidic acid cream, and emollients after a confirmed diagnosis of bullous pemphigoid was obtained. He was hospitalized for 3 weeks as a case of severe sepsis due to a skin infection, and he was started initially on empiric antibiotics with piperacillin-tazobactam plus vancomycin that was later upgraded to meropenem and vancomycin based on the results of the blood and wound cultures. The patient suffered a pulmonary embolism on the second day of hospitalization and was placed on a heparin infusion that could potentially contribute to his death one month after discharge from our hospital. CLINICAL DISCUSSION: Bullous pemphigoid is the most frequent autoimmune bullous disease. It occurs in the elderly. The cause of this disease is unknown, although it sometimes can be triggered by taking certain medications. Two case reports have also revealed bullous pemphigoid eruption following immunization. One case report reported a 78-year-old lady with diabetes and Alzheimer's disease who developed tense bullae on her face and torso after getting the second dosage of the Pfizer-BioNTech COVID-19 Vaccine. Another case study described a 77-year-old male patient who developed generalized pruritis and bullae on erythematous bases one day after receiving the AstraZeneca COVID-19 vaccination. This new-onset bullous pemphigoid phenomenon has also been observed with other vaccinations such as rabies and swine flu. CONCLUSION: Although uncommon, several dermatological side reactions like bullous eruptions have been reported following the mRNA Pfizer Covid-19 vaccination. According to this case report, Bullous pemphigoid might be caused by the mRNA- (Pfizer) Covid-19 Vaccine.

Phlegmasia Cerulea Dolens Secondary to COVID-19 and May-Thurner Syndrome: A Case Report.

Coronavirus disease 2019 (COVID-19) is associated with significant thromboembolic risk. Extensive deep vein thrombosis can infrequently progress to phlegmasia cerulea dolens that carries high morbidity and mortality rates. We report a case of a middle-aged male presenting with phlegmasia cerulea dolens in the context of COVID-19 and underlying May-Thurner syndrome, associated with transiently positive antiphospholipid antibodies.

Dual catastrophe of COVID-19: Massive pulmonary embolism and stroke in a previously healthy young patient: A case report.

We are reporting a 45-year-old woman with COVID-19 who presented to the Emergency Department with a transient loss of consciousness and was found to have a massive pulmonary embolism and an acute stroke. To our knowledge, this is the first reported case that calls for attention to the importance of vigilance for such a catastrophic presentation of COVID-19.