The coronavirus disease 2019 (COVID-19) is a highly contagious viral illness, which has spread globally, affecting millions of individuals worldwide (1). According to the World Health Organization, as of October 2023, there have been >771 million confirmed cases and >6 million deaths worldwide since the onset of the COVID-19 pandemic. To be specific, Saudi Arabia reported 841,469 confirmed cases in 2023, while the United States reported 103,436,829 cases by October 2023. These figures underscore the widespread impact of this disease (1).

Cancer patients, with their immunosuppressed status due to their condition or its treatment, are at an increased risk of infection in comparison to the general population. This immunosuppression can lead to serious complications, potentially resulting in delays of treatment and unnecessary hospitalizations, which may adversely affect the disease prognosis (2). The immunocompromised state of cancer patients may be attributed to antineoplastic therapies, supportive medications such as steroids or the immunosuppressive nature of cancer itself. In addition, immunomodulatory drugs, including programmed cell death 1 and programmed cell death ligand 1 inhibitors, can alter the immune responses to infections (3,4). Cancer patients, who are often at an advanced age (≥60 years) and have one or more significant comorbidities, are at an increased risk for COVID-19-related morbidity and mortality. These patients' frequent interactions with the healthcare system through anticancer therapies, monitoring and supportive care further elevate this risk (4). Treatment for cancer within 14 days of a COVID-19 diagnosis has been identified as a risk factor for developing severe complications, including acute respiratory distress syndrome (28.6%), septic shock (3.6%) and acute myocardial infarction (3.6%) (2). Among cancer patients diagnosed with COVID-19, a study showed that 21% succumbed to the disease as compared to 7.8% in non-cancer populations (5). Furthermore, research indicates that cancer patients diagnosed with COVID-19 are more likely to require hospitalization, intensive care unit (ICU) admission and mechanical ventilation, irrespective of the cancer type or treatment. These findings emphasize the importance of stringent infection control measures and the necessity of treating cancer patients in outpatient settings whenever feasible in order to decrease the risk (2). Given the global prevalence of cancer and the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the disease course and the factors affecting clinical outcomes in cancer patients with COVID-19 is essential (4). However, most studies performed examining cancer patients with COVID-19 have been single-center investigations, with significant variability in both inclusion criteria and outcomes. A common limitation is that many of these research endeavours and studies are case series, making it challenging to generalize findings to broader populations (5). Cancer patients represent a diverse group and there is a need for a better understanding regarding which patients, and which tumor- or treatment-related factors, are associated with an increased risk of infection and related adverse outcomes. This knowledge is crucial in determining whether an elevated COVID-19 risk should influence cancer treatment approaches (5).

The present study aims to evaluate cancer patients in terms of clinical outcomes related to COVID-19 infection, with a focus on the type of malignancy, mortality rates and other clinical outcomes. The findings of this research could be instrumental in protecting at-risk populations from COVID-19 or similar viral infections, reducing disease progression, lowering mortality and morbidity rates and ensuring optimal outcomes for cancer patients.

Sociodemographic characteristics. This review examines the findings of 27 studies (4,7-32), offering a detailed exploration of the interplay between COVID-19 and oncology. Initially, 140 studies were identified in accordance the objective for the review with 5 studies removed due to duplication, and 83 studies removed for additional reasons such as different language and non-eligible articles like case reports and brief reviews. Following the screening of 57 studies, 24 records were further excluded, as they did not meet the inclusion criteria. A total of 33 studies were further assessed for eligibility with 6 removed for reasons including the data not matching the study's purpose. Finally, 27 studies were included in the review, as they all met the eligibility criteria. The studies show diversity in sample sizes, with the study by Lee et al (7), a General Community Survey, presenting an extensive pool of 1,807,559 individuals, while a more focused cross-sectional survey by Košir et al (8) involved 177 participants. Examining the gender distribution within the COVID-19 patient cohorts revealed noteworthy patterns. In the randomized clinical trial (9), the BNT162b2 vaccine recipients showed a notable 63.9% female majority. Conversely, a retrospective cohort study by Solaini et al (10) displayed a balanced distribution among COVID-19 patients. With a focus on the impact of COVID-19 on cancer patients, Mathews et al (11) provided a detailed breakdown of 66 positive cases, demonstrating a nearly equal gender distribution among these vulnerable individuals. Meanwhile, Lee et al (7) reported 155 positive cases among 23,266 individuals with cancer, emphasizing the real-world implications of the virus in this specific population (Table I).

In this comprehensive review of the intersection of cancer and COVID-19, the findings revealed the complex dynamics influencing outcomes among cancer patients during the pandemic. The variation in sample sizes across studies, exemplified by the general community survey conducted with an extensive pool of 1,807,559 individuals and the more focused cross-sectional survey by Košir et al (8) involving 177 participants, underscores the diverse methodologies of different geographical samples and various health care systems employed in understanding this intersection. The randomized clinical trial reported by Thomas et al (9) revealed a significant 63.9% female majority among BNT162b2 vaccine recipients, while the retrospective cohort study conducted by Solaini et al (10) showcases a balanced distribution among COVID-19 patients. Shifting the focus to the impact of COVID-19 on cancer patients, Mathews et al (11) break down 66 positive cases, revealing a nearly equal gender distribution within this vulnerable group. Simultaneously, Lee et al's (7) report on 155 positive cases among individuals with cancer accentuates the tangible real-world implications of the virus within this specific population. These findings collectively contribute to our understanding of the interplay between COVID-19 and oncology.

This study thoroughly investigated the variability in outcomes among different cancer types, particularly focusing on why certain cancers, such as gastric adenocarcinoma and thoracic cancers, may exhibit higher mortality rates in COVID-19 patients. It provided an analysis of the biological and clinical factors that could contribute to these disparities. For instance, the aggressive nature of these cancers, combined with the immunosuppressive effects of both the disease and its treatments, could exacerbate the severity of COVID-19. The manuscript explores how these patients' pre-existing conditions and the potential delay in diagnosis due to the pandemic may have contributed to their heightened vulnerability.

The present study also discusses the impact of COVID-19 on cancer management and treatment decisions. It shows how the pandemic has forced alterations in standard treatment protocols, including delays in surgery, modifications in chemotherapy regimens and the adoption of telemedicine for consultations. It also sheds light on the ethical dilemmas faced by oncologists in prioritizing treatment for patients with a higher chance of survival during resource-scarce periods. Furthermore, insights into how COVID-19 has affected surgical trends and the implementation of chemotherapy protocols are well-documented, emphasizing the need for adaptive strategies in oncological care during global health crises.

In gastric adenocarcinoma, Fox et al (2022) revealed a higher mortality rate in COVID-19 patients compared to the pre-COVID era, underscoring the challenges posed by potential delays in diagnosis and treatment (33). This aligns with earlier studies emphasizing the importance of timely intervention in gastric cancers to improve survival rates (34,35). The observation of Thomas et al (9) of no mortality in individuals with a history of malignancy, coupled with high vaccine efficacy, corroborates with previous research on the potential protective effects of vaccinations in cancer patients (36).

The increased risk of COVID-19 in cancer patients, as reported by Lee et al (7), echoes concerns raised in earlier studies about the vulnerability of cancer patients to infectious diseases (37,38). Košir et al's (8) identification of a substantial impact on adolescent and young adult cancer patients aligns with broader discussions on the unique challenges faced by this demographic group during the pandemic (39,40). The decrease in cancer diagnoses and barriers to care highlighted by Dinmohamed et al (12) resonates with concerns raised in the early stages of the pandemic regarding disruptions to routine healthcare services and the downstream effects on cancer outcomes (41,42).

Breast cancer outcomes, as reported by Baba et al (14) and Resende et al (18), showcase the variability in responses to the pandemic. While the former found no significant difference in critical events, the latter identified a stage shift towards more advanced cases. These findings contribute to the ongoing discourse on the multifaceted impacts of COVID-19 on breast cancer patients, necessitating tailored approaches to care (43,44).

In lung cancer, the increased physical discomfort and psychological distress reported by Sha et al (15) highlight the broader mental health implications of the pandemic on cancer patients, an aspect that has gained prominence in recent literature (45). Aboueshia et al (16) findings of higher mortality, longer hospital stays and increased unplanned reintubations in COVID-19 patients with lung cancer emphasize the need for targeted interventions in this vulnerable population, aligning with prior research on the intersection of respiratory diseases and COVID-19 outcomes (46,47).

The study by Kuderer et al (4) on invasive or hematological malignancies signifies the severity of COVID-19 in this patient group. The observed mortality, severe illness and ICU admissions are consistent with earlier reports on the heightened risks faced by individuals with hematological malignancies during the pandemic (48). Vanni et al (21) caution about potential increases in invasive surgeries due to screening program suspensions, which echoes broader concerns about the collateral damage on cancer care caused by pandemic-related disruptions (49).

The association between hemogram parameters and COVID-19 infection has been examined in various studies (50), and parameters including the platelet-to-lymphocyte ratio (51) were found to be related to the infection. Furthermore, the red cell distribution width, a marker of anisocytosis in the hemogram, has been associated with recurrent hospitalizations of patients with COVID-19(52). Other inflammatory markers were introduced as predictors of frailty in diabetics during COVID-19(53). In addition, the role of inflammation in cancer has been reported in various studies (54,55). Furthermore, mortality is increased when markers of inflammation are elevated (56).

The high mortality and complications faced by patients with thoracic cancer, as highlighted by Passaro et al (57), underscore the critical need for specialized care in this population. Previous studies reinforce the consistent challenges faced by patients with thoracic cancer (3), emphasizing the importance of maintaining continuity in care during pandemics (58). Tokunaga et al's (23) finding of a decrease in gastrectomies for gastric cancer aligns with concerns about reduced access to surgical interventions during the pandemic, potentially impacting long-term outcomes (59,60).

Mullangi et al's (61) study on patients with lung cancer presents a unique perspective, suggesting that mortality may be more related to SARS-CoV-2 infection itself rather than to treatment delays. This observation prompts further investigation into the specific factors contributing to mortality in patients with lung cancer during the pandemic, providing a basis for tailored interventions (62).

The present meta-analysis accounts for various potential confounding factors, including age, comorbidities and cancer stage, when comparing mortality rates between COVID-19-infected cancer patients and their non-COVID counterparts. The study used multivariate analysis to determine the impact of COVID-19 on cancer outcomes, ensuring that the differences observed are not merely due to these confounders. This methodological approach enhances the reliability of the findings, providing a clearer understanding of how COVID-19 specifically affects cancer mortality rates.

The pooled analysis of 10 studies involving 5,151 cancer patients infected with COVID-19 reveals a significant overall mortality rate of 19.1%. This finding is consistent with emerging evidence highlighting the high vulnerability of cancer patients to severe outcomes of COVID-19(63). However, the substantial heterogeneity (I²=98.7%) suggests diverse outcomes across these studies, emphasizing the need for nuanced interpretations. The observed variability may be attributed to differences in patient populations, cancer types, treatment modalities and healthcare infrastructure among the included studies. The low P-value for the Q-test for heterogeneity further underscores the significance of this observed heterogeneity (P<0.0001). This variability underscores the complexity of the interaction between COVID-19 and cancer, necessitating tailored approaches to patient care (64).

By contrast, the overall mortality rate among non-COVID cancer patients, as reported by 5 studies comprising 54,528 individuals (4,9,10,14,24), was considerably lower at 0.01 (1%). This finding aligns with prior research suggesting that cancer patients not infected with COVID-19 experience relatively lower mortality rates (65). However, similar to the COVID-19-infected group, substantial heterogeneity is observed (I²=97.1%, P<0.0001). The wide range of mortality rates among non-COVID cancer patients could be attributed to variations in cancer types, stages and treatment responses.

Regarding the risk of mortality, the OR for non-COVID vs. COVID cancer patients was 0.1036 (95%CI: 0.0061 to 1.7614) based on 3 studies involving 3,496 cancer patients. The overall estimate suggests a potential decrease in mortality risk for non-COVID patients, indicating that cancer patients not infected with COVID-19 may have a comparatively lower risk of mortality (66). However, the substantial heterogeneity (I²=82.1%) signals variability among studies. Sensitivity analysis identified the study by Kuderer et al (4) as a potential source of heterogeneity. Its omission led to a lower pooled estimate (0.4473, 95% CI: 0.2026 to 0.9878), implying a subgroup with a lower mortality risk among non-COVID cancer patients. This underscores the importance of considering the characteristics of individual studies and potential sources of heterogeneity in meta-analyses to derive more accurate and clinically relevant conclusions. The identification of a subgroup with a lower mortality risk could guide further research into factors influencing outcomes in cancer patients not infected with COVID-19.

This study clarifies that while COVID-19 may worsen the prognosis for cancer patients, the mechanisms by which it does so differ significantly from other chronic diseases. For instance, the immune dysregulation caused by cancer and its treatment can create a unique vulnerability to COVID-19 that is not present in other conditions. It integrates these distinctions into its broader analysis, providing an understanding of the intersection between cancer and COVID-19.

This study carries significant implications for both clinical practice and public health. The observed high vulnerability of cancer patients to severe outcomes underscores the need for tailored interventions and prioritized care. Clinicians should be mindful of potential delays in diagnosis and treatment, particularly in gastric adenocarcinoma, and consider personalized strategies for diverse patient cohorts, as exemplified by the variability in breast cancer responses. Furthermore, the study highlights the broader mental health implications of the pandemic on lung cancer patients, emphasizing the importance of holistic care approaches. These implications necessitate ongoing efforts to integrate pandemic-specific considerations into cancer care protocols and public health strategies. The manuscript suggests that guidelines are updated to reflect the challenges posed by COVID-19, such as ensuring timely treatment while minimizing infection risks. Recommendations for improving patient outcomes may include vaccination strategies tailored to cancer patients (10,14,18,21,23,25,26).

Future research should explore specific factors influencing mortality in patients with lung cancer during the pandemic, building on the unique perspective presented by Priou et al (24). Additionally, there is a critical need for comprehensive studies investigating the long-term mental health impacts on lung cancer patients, informed by Sha et al's (15) findings. Exploring the collateral damage on cancer care, as raised by Vanni et al (21), requires in-depth investigations into the consequences of disruptions in cancer screening programs. Not all of the studies included in the present analysis adequately controlled for key confounding factors, which could have led to the introduction of bias into the pooled estimates. This variability in controlling for confounders, such as patient demographics, disease severity, cancer stage, comorbidities and treatment history, may impact the comparability of the study's outcomes and the overall robustness of the study's findings. In order to improve the reliability and accuracy of future research, the usage of more rigorous and multivariate models may be recommended, which can better adjust for these critical confounders, as it will ensure that the observed associations more accurately reflect true causal relationships. In addition, further research should focus on understanding the characteristics of the subgroup with a lower mortality risk among non-COVID cancer patients, providing insights for targeted interventions. Long-term outcomes in patients with thoracic cancer, as emphasized by Garassino et al (22), warrant dedicated research efforts to ensure continuous and specialized care during pandemics and other healthcare disruptions.

Despite the comprehensive nature of the systematic review and meta-analysis, several limitations need to be acknowledged. The inherent heterogeneity across the included studies highlights the diverse patient populations, cancer types and treatment modalities considered. This heterogeneity underscores the challenge of synthesizing data from studies with varying methodologies and emphasizes the need for cautious interpretation. The reliance on published literature may introduce publication bias, as studies with positive or statistically significant results are more likely to be published. This potential bias may affect the generalizability of findings and should be considered when extrapolating conclusions to the broader population. The dynamic nature of the COVID-19 pandemic may introduce temporal biases, with outcomes influenced by evolving healthcare practices, treatments and vaccination strategies. Furthermore, the limitations of the individual studies, such as varying sample sizes and methodologies, could impact the overall robustness of the meta-analysis. In addition, the COVID-19 pandemic has had significant effects on the various aspects of oncological care, which include chemotherapy protocols and surgical trends. For instance, surgical delays or changes and modifications in chemotherapy administration schedules have been widely reported as adaptations in order to mitigate the risk of infection and to manage healthcare resource limitations. However, due to the constraints of the included studies in the current study, which often lacked detailed information on these particular treatment adjustments, the present analysis was unable to comprehensively evaluate the extent of these pandemic-related impacts. Despite these limitations, the present study provides valuable insights into the intersection of COVID-19 and oncology, offering a foundation for future research and clinical considerations.

In conclusion, the present review signifies the high vulnerability of cancer patients to severe outcomes from COVID-19, emphasizing the need for tailored interventions and prioritized care. The variability in outcomes across different cancer types and patient cohorts highlights the nuanced nature of this intersection. Noteworthy patterns emerge, such as the differential mortality rates in gastric adenocarcinoma patients during the pandemic and the varied outcomes for vaccine recipients with a history of malignancy. The increased risk of COVID-19 among cancer patients, particularly during chemotherapy/immunotherapy, highlights the vulnerability of this population. This study not only informs immediate clinical considerations but also sets the stage for future research, aimed at refining the current understanding of the interaction between COVID-19 and oncology, ultimately improving outcomes for this vulnerable population.