(1) Background: We aimed to describe the clinical and imaging characteristics of patients diagnosed with pulmonary artery thrombosis (PAT) despite receiving anticoagulation with low-molecular-weight heparin (LMWH). (2) Methods: We retrospectively studied all hospitalized COVID-19 adult patients diagnosed with PAT between March 2020 and December 2021, who received LMWH for ≥72 h until the diagnosis of PAT. Acute PAT was confirmed by a CT pulmonary angiogram. (3) Results: We included 30 severe and critical COVID-19 patients. Median age was 62 (54–74) years, with 83.3% males, and comorbidities seen in 73.3%. PAT was diagnosed despite prophylactic (23.3%), intermediate (46.6%) or therapeutic (30%) doses of LMWH for a median time of 8 (4.7–12) days. According to their Wells score, 80% of patients had a low probability of pulmonary embolism diagnosis. PAT was localized in the lower lobes of the lungs in 76.6% of cases with 33.3% having bilateral involvement, with the distal, peripheral arteries being the most affected. At the PAT diagnosis we found a worsening of respiratory function, with seven patients progressing to mechanical ventilation (p = 0.006). The in-hospital mortality was 30%. (4) Conclusions: PAT should be considered in patients with severe and critical COVID-19, mainly in elderly male patients with comorbidities, irrespective of Wells score and LMWH anticoagulation.

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.