Observatory and Fast Facts

Jan. 19, 2022

Severe COVID tied to high risk of death, mostly by other causes, within year

Survivors of severe COVID-19 — especially those younger than 65 years — may be at more than twice the risk of dying within the next year than those who had mild or moderate illness or were never infected, finds a study in Frontiers in Medicine, according to a news release from the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota.

Another finding of the analysis of electronic health records of 13,638 patients who tested positive or negative for COVID-19 is that only 20% of those who had severe COVID-19 (requiring hospitalization) and died did so because of complications of their infection, such as abnormal blood clotting, respiratory failure, or cardiovascular problems.

Rather, 80% were due to different reasons typically considered unrelated to COVID-19.

Of all patients, 178 had severe COVID-19, while 246 were mildly or moderately ill, and the rest tested negative. Among all patients, 2,686 died within 12 months of their COVID-19 diagnosis.

Relative to uninfected patients, those recovered from severe COVID-19 younger than 65 years had a 233% increased risk of dying in the next year. The increased risk was greater than that of survivors of severe COVID-19 who were 65 years or older.

Black men undergoing radiation therapy for prostate cancer have better outcomes than White men

Individual patient data meta-analysis led by UCLA Jonsson Comprehensive Cancer Center researchers found ‘unexpected result’: Black men may have improved response to initial treatment.

UCLA Jonsson Comprehensive Cancer Center researchers leading a meta-analysis of seven randomized trials found an “unexpected result”: Although Black men appeared to have more aggressive disease when they enrolled in clinical trials of radiation therapy for prostate cancer, their treatment outcomes and disease-specific outcomes were better than those of their white counterparts.

“These results provide high-level evidence challenging the common belief that Black men who are diagnosed with prostate cancer will necessarily have a worse prognosis than white men,” said Amar Kishan, MD, Associate Professor and Vice Chair of Clinical and Translational Research in the Department of Radiation Oncology at UCLA.

“This is especially important because an unfounded belief can inadvertently contribute to ‘cancer injustice,’ leading to the use of more aggressive treatments than might be necessary — potentially reducing quality of life — and diverting attention away from other important factors that can influence outcome, including access to more comprehensive healthcare,” said Kishan, Chief of the Genitourinary Oncology Service for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center.

In what is believed to be the largest meta-analysis of its kind on the subject, the researchers reviewed individual patient data of 8,814 patients from seven randomized clinical trials on radiation therapy for prostate cancer — studies that enrolled a substantial number of Black men and were conducted by the Radiation Therapy Oncology Group (RTOG)/NRG Oncology. All patients in the trials received either standard or high-dose radiation therapy, and some patients also underwent short- or long-term androgen deprivation therapy.

Of the total, 1,630 men self-identified as Black; 7,184 as white. To investigate associations between race and treatment effectiveness, the researchers extracted and analyzed statistics on recurrence (biochemical recurrence, or BCR), metastasis (distant metastasis, or DM) and prostate cancer-specific mortality, or PCSM, and other, secondary endpoints.

According to the results, Black men were significantly younger and more likely to have high-risk disease at the time of treatment, but they had lower recurrence, metastasis, and PCSM rates than White men, even without statistical adjustment. When adjustments were made for age and other factors, “race remained significantly associated with improved BCR, DM and PCSM outcomes,” the authors reported in the article. “The fact that Black men had improved early and late disease outcomes when compared with white men is a novel and unexpected result that highlights that Black men may have an improved response to their initial treatment.”

Immunotherapy shows promise for children, young adults with recurrent AML

An immunotherapy harnessing the immune system’s “natural killer” cells has proven effective in treating acute myeloid leukemia (AML) in some adults whose cancers return. Researchers at Washington University School of Medicine in St. Louis have shown in a small clinical trial that the same natural killer cells also can help some children and young adults with recurrent AML and few other treatment options.

Results from the phase 1 trial, which included eight patients ages 1 to 30 years, are published online in the journal Blood.

“All of the patients enrolled in this study had very aggressive AML,” said Jeffrey J. Bednarski, MD, PhD, Assistant Professor of Pediatrics at Washington University School of Medicine in St Louis. “For all of them, their leukemia recurred after stem cell transplantation and was not responsive to several treatment regimens before they were referred to this study. This is a very challenging disease to treat — none of the patients had any curative options. The survival expectation for these patients was essentially zero. That three patients are still alive is very encouraging for this really challenging disease.”

Acute myeloid leukemia is a cancer of the blood and bone marrow that results in the overproduction of immature white blood cells, which crowd out healthy blood cells. Standard therapy involves chemotherapy and a stem cell transplant from a donor, which can result in a long-term remission. But for patients whose cancers return after stem cell transplantation, the disease becomes extremely difficult to treat, and most patients ultimately die from progression of their disease within a few months to a year.

Of the eight patients who received the investigational treatment, four achieved complete remission by day 28 after therapy. Two of the four stayed in remission for more than three months. One of these patients remains in remission today, more than two years after the treatment. Three patients who went into remission later relapsed. Of those three, two were able to receive a second stem cell transplant, and they’re still alive and doing well. Two other patients had a partial response to the therapy, in that their disease decreased, but they did not go into remission. The remaining two patients did not respond to the therapy.

Study shows how genetic mutation puts women at risk for ovarian cancer

Stem cell scientists have revealed the origins of a common ovarian cancer by modeling fallopian tube tissues, allowing them to characterize how a genetic mutation puts women at high risk for this cancer. The tissues, known as organoids, hold potential for predicting which individuals will develop ovarian cancer years or even decades in advance, allowing for early detection and prevention, according to a news release from Cedars-Sinai.

Ovarian cancer is the leading cause of gynecologic cancer deaths in the U.S., in part, because symptoms are often subtle, and most tumors elude detection until they are in advanced stages and have spread past the ovaries. While the lifetime risk of developing ovarian cancer is less than 2% for the general female population, the estimated risk for women who carry a mutation in the so-called BRCA-1 gene is between 35% and 70%, according to the American Cancer Society.

The new study findings could help physicians pinpoint which of these women are the most likely to deveop ovarian cancer in the future — and which are not — and pursue new ways to block the process or treat the cancer.

To make their discoveries, the research team generated induced pluripotent stem cells (IPSCs), which can produce any type of cell. They started with blood samples taken from two groups of women: young ovarian cancer patients who had the BRCA-1 mutation and a control group of healthy women. Investigators then used the IPSCs to produce organoids, modeling the lining of fallopian tubes, and compared the organoids on the two groups.

Multiple drugs can be tested on the organoids without exposing the patient to them. 

Gene therapy could hold promise for sickle cell disease

New research suggests a gene therapy called LentiGlobin could provide a cure for sickle cell disease (SCD), but the work is the early stages, according to researchers at the University of Alabama at Birmingham and reported in a news release.

Julie Kanter, MD, Director of the UAB Adult Sickle Cell Clinic, says patients treated with this therapy are beginning to show signs of producing stable amounts of normal red blood cells containing hemoglobin.

SCD occurs in about one out of every 365 Black or African American births, according to the Centers for Disease Control and Prevention (CDC), and about one in 13 Black or African American babies is born with sickle cell trait.

Kanter says there are several types of gene therapy (gene addition/transfer, gene editing, gene correction and gene silencing), but this particular therapy is gene addition or transfer therapy. “In this therapy, we do not change or edit the gene that causes sickle cell disease,” Kanter said. “Instead, we use a viral vector to deliver a new gene that will make a healthy hemoglobin — a beta hemoglobin — into the stem cell. This is like coding new instructions into the cell. The old instructions for hemoglobin S are still there, but now the cell can make HbA and HbS. The vector can deliver more than one copy of the instructions to each cell — usually between one and four copies — so the cell can make more HbA than HbS.

A vector is part of a virus. Kanter compares vectors to envelopes and letters. “I like to think of it as an envelope,” she said. “We take out the bad part of a virus (the letter) and leave the empty envelope. We put a new gene (the new letter) with the right instructions into the envelope and send it into the stem cells. The viral parts of the letter are removed so patients don’t get the virus itself — they only get the letter coding for the new hemoglobin, called HbAT87Q.”

T87Q is a special type of hemoglobin A that is slightly different from regular hemoglobin A and has two advantages:

The intentional change inserted (called T87Q) makes the hemoglobin even less likely to cause sickling when it is near a hemoglobin S.

The HbAT87Q can also be measured more accurately inside the cell (since it is slightly different from regular hbA), which allows doctors to know how much of the new hemoglobin a patient is making compared to how much they get from a transfusion.

Kanter says that, although this therapy is providing a significant amount of hope, researchers continue to test to make sure the therapy remains safe.