Introduction

Cancer patients represent a uniquely vulnerable population during the COVID‑19 pandemic due to the combined effects of malignancy‑related immune dysregulation and treatment‑induced immunosuppression. Since the emergence of SARS‑CoV‑2, accumulating evidence has demonstrated that patients with active cancer experience higher rates of severe infection, complications, and mortality compared with the general population. This increased susceptibility is multifactorial and involves impaired innate and adaptive immunity, chronic inflammation, and endothelial dysfunction, all of which may be further exacerbated by systemic anticancer therapies such as chemotherapy (1).

Chemotherapy remains a cornerstone of cancer treatment across a wide range of solid and hematologic malignancies; however, its immunosuppressive effects raise substantial concerns in the context of concurrent viral infections. Cytotoxic agents can induce neutropenia, lymphopenia, and functional immune impairment, potentially facilitating viral replication and progression to severe disease. During the COVID‑19 pandemic, clinicians have faced difficult decisions regarding the continuation, delay, or modification of chemotherapy regimens, particularly in patients who test positive for SARS‑CoV‑2 or develop COVID‑19 related symptoms while undergoing treatment (2).

Beyond respiratory involvement, COVID‑19 is now recognized as a systemic disease with profound effects on the vascular and coagulation systems. SARS‑CoV‑2 infection is strongly associated with a hypercoagulable state characterized by endothelial injury, platelet activation, cytokine‑mediated inflammation, and dysregulation of the coagulation cascade. These mechanisms contribute to an increased incidence of both venous and arterial thrombotic events, including deep vein thrombosis, pulmonary embolism, myocardial infarction, and acute ischemic stroke (3). Thrombotic complications are particularly relevant in patients with cancer, who already possess an inherently elevated baseline risk of thrombosis. Malignancy‑associated hypercoagulability arises from tumor‑derived procoagulant factors, inflammatory cytokine release, endothelial activation, and interactions between cancer cells and platelets. Chemotherapy further amplifies this risk by inducing endothelial damage, promoting inflammatory responses, and altering hemostatic balance. The coexistence of cancer, chemotherapy, and COVID‑19 may therefore create a synergistic prothrombotic milieu with serious clinical consequences (4).

Acute ischemic stroke has emerged as a notable complication of COVID‑19, even among younger patients and those without traditional vascular risk factors. COVID‑19 related strokes are often characterized by large‑vessel occlusion, high clot burden, and poor functional outcomes. Mechanical thrombectomy has become the standard of care for selected patients with large‑vessel occlusive stroke, offering substantial benefits in terms of reperfusion and neurological recovery. However, outcomes after thrombectomy in the setting of active COVID‑19 infection appear to be less favorable than in non‑infected patients (5). In patients with cancer, stroke outcomes are often worse compared with non‑cancer populations, owing to advanced age, comorbidities, cancer‑related coagulopathy, and limited physiological reserve. Cancer‑associated strokes are more likely to be multifocal, recurrent, and resistant to standard antithrombotic therapies. When COVID‑19 infection and chemotherapy exposure coexist, the biological complexity increases further, potentially influencing procedural success, peri‑procedural complications, and post‑thrombectomy recovery (6).

The inflammatory response triggered by SARS‑CoV‑2 plays a central role in both thrombogenesis and disease severity. Elevated levels of inflammatory markers such as C‑reactive protein, interleukin‑6, and tumor necrosis factor‑alpha have been associated with endothelial injury, platelet aggregation, and fibrin formation. Chemotherapy can modulate this inflammatory response in unpredictable ways, either attenuating cytokine release through immunosuppression or exacerbating tissue injury and systemic inflammation depending on the agents used and patient characteristics (7). Endothelial dysfunction represents a key pathophysiological link between COVID‑19, cancer, and thrombosis. SARS‑CoV‑2 directly infects endothelial cells via angiotensin‑converting enzyme 2 receptors, leading to endothelialitis, microvascular injury, and prothrombotic transformation. Cancer and chemotherapy independently induce endothelial damage, impair nitric oxide production, and promote a pro‑adhesive vascular environment. These converging insults may adversely affect cerebral microcirculation and reperfusion success following mechanical thrombectomy (8).

Clinical data regarding thrombectomy outcomes in cancer patients with concurrent COVID‑19 infection remain limited. Most available studies have examined COVID‑19 related stroke in the general population, often excluding patients with active malignancy or recent chemotherapy. As a result, the combined impact of cancer biology, chemotherapy‑induced immunosuppression, and SARS‑CoV‑2 associated coagulopathy on thrombectomy outcomes is poorly understood. This represents a critical knowledge gap with direct implications for acute stroke management (9).

Peri‑procedural considerations are particularly complex in this population. COVID‑19 positive patients undergoing thrombectomy may experience delays in presentation, imaging, and intervention due to infection control measures. Additionally, chemotherapy‑related cytopenias, including thrombocytopenia and anemia, may increase the risk of hemorrhagic transformation or procedural complications. These factors may influence both short‑term neurological outcomes and overall survival following thrombectomy (10).

The severity of COVID‑19 infection may further modify outcomes in patients undergoing thrombectomy. Severe COVID‑19 is associated with hypoxemia, hemodynamic instability, and multiorgan dysfunction, all of which can negatively impact cerebral perfusion and post‑stroke recovery. In patients receiving chemotherapy, the risk of severe COVID‑19 may be heightened, potentially compounding the adverse effects of acute ischemic stroke and limiting rehabilitation potential (11). Another important consideration is the potential interaction between anticoagulation strategies, cancer‑associated thrombosis, and COVID‑19 related coagulopathy. While anticoagulation is frequently employed in hospitalized COVID‑19 patients, optimal dosing and timing remain controversial, particularly in patients with recent stroke or those undergoing invasive procedures such as thrombectomy. Chemotherapy‑related bleeding risk further complicates decision‑making in this high‑risk population (12). From a prognostic perspective, overall survival and functional outcomes following thrombectomy may be influenced not only by neurological factors but also by cancer stage, treatment intent, and life expectancy. In patients with advanced or progressive malignancy, the benefits of aggressive stroke intervention must be weighed against goals of care and quality of life considerations. COVID‑19 infection may further shift this balance by increasing short‑term mortality risk and complicating oncologic management (13). Despite these challenges, mechanical thrombectomy remains a potentially life‑saving intervention, and withholding treatment solely based on cancer diagnosis or COVID‑19 status may not be justified. A nuanced understanding of how concurrent COVID‑19 infection and chemotherapy influence thrombectomy outcomes is essential to guide individualized clinical decision‑making and resource allocation, particularly during pandemic conditions (14). To date, few studies have specifically examined thrombectomy‑related outcomes in patients with cancer receiving chemotherapy who simultaneously infected with SARS‑CoV‑2. Existing evidence is largely derived from small case series or retrospective analyses with heterogeneous populations and limited adjustment for confounding factors. High‑quality data are urgently needed to clarify procedural success rates, complication profiles, and survival outcomes in this complex clinical scenario (15).

Therefore, the present study aims to evaluate the impact of concurrent COVID‑19 infection and chemotherapy on thrombectomy‑related outcomes in patients with cancer. By focusing on this high‑risk population, this investigation seeks to provide clinically relevant insights into neurological recovery, procedural complications, and short‑term outcomes, ultimately contributing to evidence‑based management strategies for stroke care in cancer patients during the COVID‑19 era.

Material and methods

Study Design: This study was designed as a descriptive–analytical observational investigation conducted after obtaining approval from the Regional Ethics Committee of Tabriz University of Medical Sciences. Following ethical approval and coordination with Imam Reza Hospital, data collection was carried out prospectively by a trained research assistant (medical intern and thesis owner) using standardized data collection forms for each eligible patient.

Sample Size Estimation and Sampling Method: Given the exploratory nature of the study and the limited availability of eligible patients, sample size estimation was based on feasibility rather than formal power calculation. All eligible patients meeting the inclusion criteria during the study period were enrolled using a convenience sampling method until the maximum achievable sample size was reached.

Inclusion and Exclusion Criteria: Eligible participants included adult patients with a confirmed diagnosis of malignancy who were admitted to the intensive care unit and had documented COVID‑19 infection, with or without a history of chemotherapy. Patients were required to have complete clinical records and laboratory data at the time of ICU admission. Individuals were excluded if they had incomplete medical records, unclear cancer diagnosis, absence of confirmed COVID‑19 infection, or if essential outcome data such as ICU course or mortality status were missing.

Study Procedures: After enrollment, a dedicated case report form was completed for each patient. Baseline demographic data including age, sex, body mass index, and comorbid conditions such as hypertension, diabetes mellitus, cardiovascular disease, chronic pulmonary disease (including asthma and COPD), renal disorders, and liver disease were systematically recorded. Cancer‑related variables including primary tumor site (breast, brain and spine, lung, gastrointestinal tract, reproductive system, thyroid) and history of chemotherapy documented. Laboratory parameters obtained at ICU admission were collected, including platelet count, white and red blood cell counts, hemoglobin, hematocrit, prothrombin time, partial thromboplastin time, C‑reactive protein, D‑dimer, fibrinogen, and ferritin levels. Clinical outcomes such as length of ICU stay, total hospital stay, requirement for mechanical ventilation, ICU mortality, and discharge status from the ICU were recorded. Information regarding anticoagulant therapy prior to ICU admission and during ICU hospitalization was also documented. Additionally, the anatomical location of thrombotic involvement including upper and lower extremity arteries and veins, carotid arteries, aorta and its branches, pulmonary embolism, cerebral vessels, and coronary vessels was systematically registered.

Statistical Analysis: Data analysis was performed using SPSS statistical software. Continuous variables were expressed as mean ± standard deviation or median with interquartile range, depending on data distribution, while categorical variables were presented as frequencies and percentages. Comparisons between groups were conducted using appropriate parametric or non‑parametric tests. A p‑value of less than 0.05 was considered statistically significant in all analyses.

Ethical Considerations: This study was approved by the Ethics Committee of Tabriz University of Medical Sciences (Ethics Code: IR.TBZMED.REC.1403.021). All patient data were collected anonymously and handled confidentially in accordance with ethical standards and the Declaration of Helsinki. No identifying personal information was disclosed, and access to the dataset was restricted to the research team only.

Results

The study population comprised 120 critically ill cancer patients admitted to the ICU with concurrent COVID‑19 infection, with a mean age of 61 years, reflecting a predominantly older cohort with substantial comorbidity burden. Males constituted a slight majority, and the average body mass index indicated an overall overweight population. Hypertension and diabetes were the most prevalent comorbid conditions, followed by established cardiovascular disease, underscoring the high baseline vascular risk profile of the cohort. Pulmonary, renal, and hepatic comorbidities were also frequently observed, which may have contributed to disease severity and adverse outcomes. Lung and breast cancers represented the most common primary malignancies, although a broad spectrum of tumor sites was included, enhancing the generalizability of the findings. Notably, nearly two‑thirds of patients had a documented history of chemotherapy prior to ICU admission, highlighting the immunocompromised status of a substantial proportion of the cohort. Additionally, approximately one‑third of patients were receiving anticoagulant therapy before ICU admission, reflecting pre‑existing thrombotic risk or prior cardiovascular indications. Collectively, these baseline characteristics describe a clinically complex population at high risk for thrombotic and adverse critical care outcomes (table 1).

 Table 1. Baseline Demographic and Clinical Characteristics of the Study Population

Laboratory findings at ICU admission demonstrated a pronounced inflammatory and hypercoagulable state across the cohort, as evidenced by markedly elevated levels of C‑reactive protein, D‑dimer, fibrinogen, and ferritin, alongside mild anemia and coagulation parameter prolongation. These abnormalities are consistent with the combined effects of severe COVID‑19 infection, active malignancy, and prior exposure to chemotherapy. Thrombotic events were common and involved multiple vascular territories, with pulmonary embolism and cerebral vessel thrombosis representing the most frequent sites, followed by extremity, carotid, aortic, and coronary involvement, highlighting the systemic nature of thromboinflammation in this population. Clinically, patients experienced prolonged ICU and hospital stays, and more than half required mechanical ventilation, reflecting severe respiratory and multisystem compromise. Anticoagulant therapy was administered to the majority of patients during ICU admission, underscoring the high perceived thrombotic risk. Despite intensive management, ICU mortality remained substantial, emphasizing the poor short‑term prognosis of critically ill cancer patients with COVID‑19 complicated by thrombotic events (table 2).

Table 2. Laboratory Findings, Thrombotic Characteristics, and Clinical Outcomes of ICU‑Admitted Cancer Patients with COVID‑19

Figure 1 illustrates the distribution of thrombotic events among critically ill cancer patients with concurrent COVID‑19 infection, revealing a clear predominance of pulmonary embolism and cerebral vessel thrombosis compared with other vascular territories. This pattern underscores the profound systemic hypercoagulable state induced by the combined effects of SARS‑CoV‑2 related endothelial injury, malignancy‑associated thrombophilia, and chemotherapy‑related vascular toxicity. The involvement of multiple arterial and venous beds, including extremity, carotid, aortic, and coronary vessels, further highlights the diffuse nature of thromboinflammation in this high‑risk population. Collectively, these findings emphasize that thrombotic complications in this setting are not confined to a single anatomical site but represent a widespread pathophysiological process, likely contributing to the observed severity of clinical outcomes and elevated ICU mortality.

Figure 1. Distribution of Thrombotic Events in Critically Ill Cancer Patients with Concurrent COVID‑19 Infection

 Figure 2 presents Kaplan Meier overall survival curves stratified by chemotherapy status in cancer patients with concurrent COVID‑19 infection, demonstrating a clear divergence in survival probabilities over time. Patients receiving active chemotherapy exhibited an earlier and steeper decline in survival compared with those not undergoing chemotherapy, suggesting increased vulnerability to adverse outcomes in the acute phase of infection. This difference likely reflects the combined impact of treatment‑related immunosuppression, heightened inflammatory response, and COVID‑19 associated coagulopathy. The temporal separation of the curves underscores chemotherapy status as a clinically relevant modifier of short‑term prognosis in this high‑risk population, with important implications for risk stratification and intensive care decision‑making.

Figure 2. Kaplan Meier Overall Survival Stratified by Chemotherapy Status in Cancer Patients with Concurrent COVID‑19 Infection