SARS-CoV-2 RT-PCR-Positive Test Not Significantly Correlated with Risk of Death

Results from the PRE-ONCOVID-19 study of patients with cancer suspected of having coronavirus disease 2019 (COVID-19) infection suggested that the death rate at 30 days after diagnosis is high, both in patients with and without documented SARS-CoV-2 infection on reverse-transcriptase PCR (RT-PCR).

“Importantly, the presence of a SARS-CoV-2 RT-PCR-positive test was not significantly correlated to the risk of death in the overall population in univariate or multivariate analysis,” the authors wrote.

The retrospective study, published in the European Journal of Cancer, focused on 302 patients with cancer who were admitted to the Comprehensive Cancer Center of Lyon in France between March and April 2020 with fever, dry cough, dyspnea, dysgeusia, anosmia, diarrhea, and/or suspicious images on computed tomography (CT), with or without contact with a suspected COVID-19 patient.

Of the total cohort, only 55 patients (18.2%) with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. This patient population tended to be older and had more frequent hematological malignancies, respiratory symptoms, and suspected COVID-19 pneumonia. However, 38% and 20% of SARS-COV-2 RT-PCR-negative patients presented with similar respiratory symptoms and CT scan images, respectively.

Comorbidities (smoking history, obesity, COPD, diabetes, and hypertension) were similar in both patient populations. Additionally, the biological characteristics of both patient populations were also similar, as both populations presented with similar major lymphopenia and a major inflammatory syndrome with increased CRP levels, as well as an accurate surrogate of circulating interleukin (IL)-6 levels reported to be increased in severe COVID-19.

Ultimately, 30 patients (9.9%) died during the observation period, including 24 (80%) who had advanced disease. At a median follow-up of 25 days after the first symptoms, the death rate in RT-PCR-positive and RT-PCR-negative patients were 21% and 10%, respectively. 

Notably, multivariate analysis indicated that mortality risk was significantly and independently predicted by fever plus respiratory symptoms (hazard ratio [HR] = 5.09), a Karnofsky performance status score of less than 60 (HR = 4.87), relapsing cancer (HR = 3.05), a lymphocyte count below 700/µL (HR = 3.05), and male sex (HR = 2.75).

Detection of SARS-CoV-2 on RT-PCR was not correlated with an increased death rate though (P = 0.10). Moreover, none of the treatments given to the study cohort within the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2, etc.) correlated with survival.

Overall, the survival of both RT-PCR-positive and -negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CT scan was similar with an 18.4% and 19.7% death rate at day 25. However, the majority of patients with cancer dying during this period (22 of 30, 73%) were RT-PCR negative.

“These observations strongly suggest an underdiagnosis of COVID-19 in this population of cancer patients and a major underestimation of SARS-COV-2 contribution as a cause of death in cancer patients,” the authors wrote. “The management of cancer patients with febrile respiratory symptoms in this period of epidemic should therefore be particularly careful even in the absence of SARS-COV-2 detection.”

According to the investigators, clinical trials for this patient population remain ongoing, with immunotherapies, chloroquine analogues, or anti-IL-6 being tested (Immunoncovid-20, NCT04333914).

The researchers also added that, “[s]pecific therapeutic procedures suggested to improve COVID-19 patient survival, e.g. anti-IL-6 Ab, chloroquine analogues, remdesivir (Veklury), should be investigated also in this SARS-COV-2-negative cancer patient population presenting with severe symptoms suggestive of COVID-19.”

References:

Assaad S, Avrillon V, Fournier M, et al. High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR. European Journal of Cancer. doi:10.1016/j.ejca.2020.05.028.