In a comprehensive analysis of patients with cancer who had exceptional responses to therapy, researchers have identified molecular changes in the patients’ tumors that may explain some of the exceptional responses, according to the National Institutes of Health (NIH).
The study defined an exceptional responder as someone who had a partial or complete response to a treatment that would be effective in less than 10 percent of similar patients. The duration of an exceptional response is one that lasts at least three times longer than the median response time.
The results demonstrate that genomic characterizations of cancer can uncover genetic alterations that may contribute to unexpected and long-lasting responses to treatment. The results appeared in Cancer Cell. Researchers at the National Cancer Institute (NCI), part of the NIH, conducted the study in collaboration with investigators from other institutions, including NCI-designated Cancer Centers.
The retrospective study, which is now closed to accrual, included detailed medical histories and tumor samples from 111 patients with various types of cancer who had received standard treatments, such as chemotherapy. The patients had been identified by NCI’s Exceptional Responders Initiative, a national project launched in 2014 to explore the feasibility of collecting and analyzing the data and biospecimens needed to better understand the biological basis of exceptional responses in cancer.
For 26 of the 111 (24 percent) patients, the researchers were able to identify molecular features that could potentially explain exceptional responses to treatment, such as the co-occurrence of multiple rare genetic changes in the tumor genome or the infiltration of the tumor with certain types of immune cells.
To analyze the tumor tissue (and normal tissue, when available) from patients in the study, the researchers used multiple genomic approaches — including analysis of DNA mutations, RNA expression levels, DNA copy number alterations, and DNA methylation — as well as analysis of the immune cells in the tumor microenvironment.
The mechanisms underlying exceptional responses in the study fit into several broad categories, including the body’s ability to repair DNA damage and the immune system’s response to tumors. Another category described rare combinations of genomic alterations that resulted in the death of tumor cells during treatment — a concept known as synthetic lethality.
For example, the researchers identified mutations in the BRCA1 or BRCA2 genes in two patients with cancers that rarely involve alterations in these genes, which help repair DNA. But in these patients, the researchers suggested, the mutations may have impaired the tumor’s ability to fix damaged DNA, thereby increasing the effectiveness of treatments such as platinum-based chemotherapy that harm DNA.
Autopsied hearts suggest myocarditis link to COVID-19 may be uncommon
Following a recent review of clinical findings from 277 hearts autopsied from people in nine countries who died from COVID-19, researchers at Johns Hopkins Medicine and Louisiana State University suggest that myocarditis, an inflammation of the heart muscle, related to COVID-19 may be a rare occurrence, according to a press release from Johns Hopkins Medicine.
That finding contradicts the results of a German research study, which suggested that 60 out of 100 patients who had recovered from the coronavirus showed signs of the dangerous heart condition via MRI.
The study from Johns Hopkins Medicine and Louisiana State University was published online in the journal Cardiovascular Pathology.
In this study, the data from the autopsied hearts were published in 22 papers. After careful review, the researchers determined that the rate of myocarditis found in these patients is between 1.4 percent and 7.2 percent. Earlier studies, using imaging of hearts rather than a physical examination of the organs following death, reported rates ranging between 14 percent and 60 percent.
The researchers said that even a low myocarditis rate of 1.4 percent would predict hundreds of thousands of worldwide cases of myocarditis following severe COVID-19. Low rates of myocarditis, they added, do not indicate that individuals infected with SARS-CoV-2 are not having cardiovascular problems, but rather those complications are likely due to other factors such as immune responses or electrolyte imbalances.
Based on the results of their study, the researchers have created a checklist for pathologists to use when evaluating COVID-19 at autopsy to provide consistency in investigating and reporting cardiovascular pathologic findings.
Benefits of high-dose blood thinners in COVID-19 patients unclear
While COVID-19 infected patients should be treated with standard anticoagulation therapies, such as blood thinning medication, a new study by researchers at the George Washington University (GW) suggested that anticoagulating patients at higher doses, without traditional medical indications to do so, may be ineffective and even harmful, according to a press release.
The study was published in the journal Thrombosis Research.
The research team evaluated 402 patients diagnosed with COVID-19 admitted to GW Hospital between March 15 and May 31, 2020. Clinical outcomes were compared between 152 patients treated with high-dose blood thinners, and 250 patients treated with the standard low-dose blood thinners, typically prescribed to hospitalized medical patients.
“While it’s true that COVID-19 patients could be dying of blood clots, the data we’ve evaluated does not support giving every patient a high dose of blood thinners. That’s a challenge, as the benefits still remain unclear,” said Lei Lynn, MD, first author of the study and Assistant Professor of Medicine at GW. “We caution against an aggressive blood thinner regimen for everyone, unless there is clear evidence to do so.”
At the beginning of the pandemic, all patients admitted with COVID-19 to the GW Hospital were treated with standard dose anticoagulation, unless contraindicated. As awareness of the elevated risk of blood clots developed, many providers began treating patients with high-dose blood thinners. At GW Hospital, for non-critically ill patients, medical teams were advised to especially consider initiating a high dose of anticoagulation if a patient’s D-dimer level exceeded 3 micrograms per milliliter. The research team previously published a study finding higher levels of the biomarker D-dimer, a medical indicator found in the blood, is associated with higher odds of clinical deterioration and death from COVID-19.
Details of brain damage in COVID-19 patients
One of the first spectroscopic imaging-based studies of neurological injury in COVID-19 patients has been reported by researchers at Massachusetts General Hospital (MGH) in the American Journal of Neuroradiology, according to a press release.
Looking at six patients using a specialized magnetic resonance (MR) technique, they found that COVID-19 patients with neurological symptoms show some of the same metabolic disturbances in the brain as other patients who have suffered oxygen deprivation (hypoxia) from other causes, but there are also notable differences.
While it is primarily a respiratory disease, COVID-19 infection affects other organs, including the brain. It is thought that the disease’s primary effect on the brain is through hypoxia, but few studies have documented the specific types of damage that distinguish COVID-19-related brain injury. Several thousand patients with COVID-19 have been seen at the MGH since the outbreak began early this year, and this study included findings from three of those patients.
The researchers used 3 Tesla Magnetic Resonance Spectroscopy (MRS), a specialized type of scanning that is sometimes called a virtual biopsy. MRS can identify neurochemical abnormalities even when structural imaging findings are normal. COVID-19 patients’ brains showed N-acetyl-aspartate (NAA) reduction, choline elevation and myo-inositol elevation, similar to what is seen with these metabolites in other patients with white matter abnormalities (leukoencephalopathy) after hypoxia without COVID-19.
One of the patients with COVID-19 who showed the most severe white matter damage (necrosis and cavitation) had particularly pronounced lactate elevation on MRS, which is another sign of brain damage from oxygen deprivation.
Two of the three COVID-19 patients were intubated in the intensive care unit at the time of imaging, which was conducted as part of their care. One had COVID-19-associated necrotizing leukoencephalopathy. Another had experienced a recent cardiac arrest and showed subtle white matter changes on structural MR. The third had no clear encephalopathy or recent cardiac arrest. The non-COVID control cases included one patient with white matter damage due to hypoxia from other causes (post-hypoxic leukoencephalopathy), one with sepsis-related white matter damage, and a normal, age-matched, healthy volunteers.
Large reference laboratories go direct-to-consumer with COVID-19 services
The large reference laboratories have been developing COVID-19 tests and services that they can sell directly to consumers. For medical oversight, the labs typically contract with physicians, who prescribe the COVID-19 molecular tests and counsel patients. Web portals connect providers and patients.
The latest move in this trend goes one step further. LabCorp Diagnostics announced that it has received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) to make the Pixel by LabCorp COVID-19 Test Home Collection Kit available to consumers over the counter without a prescription, although physicians are available electronically to counsel patients with positive test results.
The kit is currently available through the Pixel by LabCorp website, and the company said in a news release that “this approval will enable LabCorp to potentially distribute the kit through retail channels.” LabCorp encourages interested retailers to reach out to the company on its website.
“With the first over-the-counter at-home collection kit ever authorized by the FDA for COVID-19, we are empowering people to learn about their health and make confident decisions,” said Brian Caveney, MD, Chief Medical Officer and President of LabCorp. With this authorization, we can help more people get tested, reduce the spread of the virus and improve the health of our communities.”
After purchase, users register their Pixel by LabCorp COVID-19 collection kit on the website and follow the instructions included. Test results are delivered to the consumer via the LabCorp portal.
Both LabCorp and Quest Diagnostics also have been selling at-home COVID-19 collection kits to consumers through web portals.
For example, Quest works with an independent network of physicians who review patients’ symptoms through an online process, and then prescribe the test if they deem it to be medically appropriate. Quest mails the test kit to consumers, who have two options to collect their specimen: do it themselves at home or take the kit to a drive-through Walmart pharmacy for assistance.
In either case, they mail the specimen back to Quest using a pre-paid, lab-provided shipping envelope. They log on to Quest’s web portal to view their test results. Quest and Walmart even have experimented with drone delivery of the test kits to single-family homes in Las Vegas and Cheektowaga, NY.
