High COVID-19 False-Negative Rate Among Patients With Hematological Malignancies

There is a high false-negative rate of coronavirus disease 2019 (COVID-19) in patients with hematological malignancies, according to study findings presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

The findings suggested the need to establish the diagnosis of COVID-19 quickly, as faster initiation of treatment was associated with better outcomes.

Alex Niu, MD, Section of Hematology and Medical Oncology, Department of Medicine, Tulane University, and a team of investigators examined 29 patients with a variety of hematological malignancies with high suspicion for COVID-19 based on clinical presentation, lab results, and imaging. Patients, aged 24-82 years old, were tested with CRISPR and/or RT-PCR based techniques.

Those included had a variety of hematological malignancies—20 lymphoid and 9 myeloid. Of the patients, 24 presented with an undiagnosed respiratory illness and 5 presented while asymptomatic for testing prior to chemotherapy. All patients were evaluated for COVID-19.

Among the patients, 16 tested positive for COVID-19 with guideline-directed nasopharyngeal RT-PCR testing, including 5 asymptomatic. There were 13 patients who tested negative but based on their clinical history, imaging, and disease course, there was still concern the patients were infected.

The team used CRISPR technology to test 8 patients who initially tested negative by RT-PCR. Of those re-tested, 7 of the 8 patients tested positive for COVID-19 with a blood sample and/or nasal swab for the SARS-CoV-2 specific N gene and ORF1ab gene. Without the patients who were negative and not tested by CRISPR, the rate of false negativity with RT-PCR testing was elevated at 29% in the team’s cohort of hematological malignancies.

There was a very high fatality rate observed, with 31% of patients dying. For the 23 patients who tested positive, 8 patients received COVID-19-directed therapy with either hydroxychloroquine/azithromycin, remdesivir, and/or COVID-19 convalescent plasma, and 4 patients died. Of the 8 patients, 7 improved and 1 died.

Among the 5 patients who were negative with no CRISPR completed, 1 received hydroxychloroquine/azithromycin due to symptoms and imaging and recovered. Three patients died outside the facility due to unknown causes.

A majority of the patients included in the study had undergone SCT or were actively on chemotherapy. Most were on lymphodepleting chemotherapy. Symptoms and immune response to COVID-19 were likely to differ from immunocompetent patients, which resulted in an overall worse outcome in the patients. The 5 asymptomatic patients had lymphoid malignancies and were on chemotherapy.

For patients with hematological malignancies, investigators noted the need to establish an algorithm to diagnose COVID-19 efficiently. Treatment pathways must also be instituted to treat the infection and provide the best treatment for the underlying hematological malignancies.

The study, “COVID-19 in Patients with Hematological Malignancies: High False Negative Rate with High Mortality,” was presented at the 62nd ASH Annual Meeting and Exposition.