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Severe COVID-19 raises alarm for undiagnosed cancer


Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic reported that male sex, older age, and comorbidities such as chronic diseases and active cancers increased the risk of hospitalization and mortality due to SARS-CoV-2 infection. Individuals with active cancers were also at a relatively higher risk of COVID-19-associated mortality, even if they were vaccinated.

The six factors that increased the morbidity and mortality risk of cancer patients to SARS-CoV-2 infections were age, increased expression of the angiotensin-converting enzyme 2 (ACE-2) receptor transmembrane serine protease 2 (TMPRSS2), immunosuppression due to cancer treatments, as well as a pro-coagulant state and inflammatory responses induced by cancer. Some of these factors could influence the susceptibility to severe SARS-CoV-2 infections in individuals with undiagnosed cancers.

About the study

In the present study, researchers used data from the French Système National des Données de Santé (SNDS) database. This database has been used for various pharmacological and epidemiological studies, as it comprises healthcare reimbursement data for the entire population of France.

The SNDS database consists of one section with information on ambulatory medical care reimbursements, including laboratory tests, ambulatory medical care, and prescription drugs, whereas the other section consists of information on hospital admissions, discharges, medical procedures, and diagnoses.

From anonymized data, specific medical algorithms were used to identify pathologies, causes for hospitalization, long-term illness diagnoses, and treatment reimbursements. The study included data on intensive care unit (ICU) admissions between February 15, 2020, and August 31, 2021, which covered the period between the onset of the COVID-19 pandemic and the end of the fourth wave in France. The follow-up was extended to the end of December 2021 to allow for a four-month follow-up for ICU-admitted patients.

The study included data on individuals above the age of 16 who had availed of at least one reimbursement in the two years before the index date and had no cancer diagnoses in the previous five years. Nursing home residents and twins below the age of 22 were excluded from the study.

Study participants were categorized into two groups, the first of which included those admitted into the ICU. The second group included age, sex, and French department-matched controls who were not hospitalized.

Information on sex, age, area of residence, and socio-economic status were determined, and co-variables such as existing comorbidities, COVID-19 vaccination status, treatment with corticosteroids or immunosuppressants, and addictive disorders were analyzed.

The examined outcome included the incidence of cancer during the follow-up period in either of the two groups. An incidence of cancer was defined as hospitalization due to any cancer or cancer-like condition requiring reimbursement.

Participants were excluded from the analysis after the initial inclusion in case of death in either of the groups. Additionally, individuals from the control group who were hospitalized due to SARS-CoV-2 infection were subsequently removed from the control group and added to the ICU-admission group.

COVID-19 hospitalization and increased risk of cancer

A total of 897 of the 41,302 individuals admitted to the ICU with SARS-CoV-2 infection were diagnosed with cancer during the follow-up months as compared to 10,944 of the 713,670 controls diagnosed with cancer. In fact, individuals who had been admitted to the ICU had a 1.31 times higher risk of a cancer diagnosis than those who did not require hospitalization for SARS-CoV-2 infection.

When the follow-up period was decreased to three months or if only the female population was considered, the association between ICU admission and cancer diagnosis was stronger. Furthermore, as compared to controls, individuals in the ICU group were more likely to be diagnosed with hematological, renal, lung, or colon cancers. Other types of cancers did not show significant differences between the two groups.

While the study did not discuss any causal effect between SARS-CoV-2 infection and the development of cancer during the follow-up period, the researchers speculated on the differences in the screening and diagnosis techniques between the two groups that could have led to a detection bias.

Individuals admitted to the ICU with SARS-CoV-2 infection might have been subjected to repetitive lung scans and blood tests, which may have led to the detection of lung or hematological cancers. Comparatively, prostate-specific antigen tests or mammograms might not have been a priority during the ICU admission, thereby resulting in lower detection of prostate or breast cancers, respectively.

In contrast, individuals in the control group might have been screened for other cancers, as they were in a better health condition to undergo these tests.


Individuals who experienced severe SARS-CoV-2 infection requiring ICU admission were at a greater risk of being diagnosed with cancer during the following months than individuals who did not require hospitalization for COVID-19. While there is a potential for detection bias, these results indicate that severe SARS-CoV-2 infection could be a marker for undiagnosed cancer.

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