From COVID Screening to Cancer Outcomes: Scientific Investigations Address COVID-19 and Cancer
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Since the start of the pandemic in early 2020, faculty at the NCI-designated Herbert Irving Comprehensive Cancer Center at Columbia University Vagelos College of Physicians and Surgeons and the Weill Cornell Medicine Meyer Cancer Center in partnership with NewYork-Presbyterian have contributed their expertise and resources to scientific investigations of COVID-19 and its implications for oncology patients.
Our cancer centers are also members of the COVID-19 and Cancer Consortium (CCC19), which has over 120 cancer centers and other organizations “who have come together to collect and disseminate prospective, granular, uniformly organized information on people with cancer who are diagnosed with COVID-19 – at scale and as rapidly as possible.”
Following are several studies by Columbia University and Weill Cornell Medicine faculty aimed at better understanding SARS-CoV-2 and its relationship to cancer.
Screening for COVID-19 in Asymptomatic Patients with Cancer
During the pandemic, oncologists across the country shared a common concern on how to continue providing cancer care while protecting patients and minimizing exposure to healthcare staff. Faculty in the Division of Hematology and Medical Oncology at Weill Cornell Medicine, led by Manish A. Shah, MD, Director of Gastrointestinal Oncology and a member of the Weill Cornell Medicine Meyer Cancer Center, created separate units for cancer patients with confirmed COVID-19, those with symptomatic but unconfirmed COVID-19, and asymptomatic patients not at high risk because of no known exposures to COVID-19. For symptomatic patients who required cancer care, they implemented a SARS-CoV-2 testing/screening protocol.
From April 30 through June 2, 2020, the Weill Cornell Medicine team performed 621 PCR tests on 537 asymptomatic patients with hematologic or solid tumor malignant neoplasms. More than 90 percent of patients were receiving active cytotoxic or targeted therapy. The study findings, published in JAMA Network Open in September 2020, showed that the rate of past infection in the clinically screened asymptomatic cancer population was exceptionally low at approximately 4 percent, and the rate of SARS-CoV-2 PCR positivity was less than 1 percent.
The researchers concluded that patients whose test results were negative for COVID-19 could receive chemotherapy without increasing the risk of contracting the disease, further strengthening the argument that clinicians may resume anticancer therapy in asymptomatic patients.
Shah MA, Mayer S, Emlen F, Sholle E, Christos P, Cushing M, Hidalgo M. Clinical Screening for COVID-19 in Asymptomatic Patients with Cancer. JAMA Network Open. 2020 Sep 1;3(9):e2023121.
Does Chemotherapy Increase the Risk for Developing COVID-19?
Seeking to understand what demographic, clinical, tumor- and treatment-related factors are associated with developing COVID-19 among patients with cancer, Columbia University researchers conducted an investigation to determine if patients receiving chemotherapy were at increased risk for developing COVID-19.
The retrospective study, led by Katherine D. Crew, MD, MS, Director of the Clinical Breast Cancer Prevention Program at Columbia University, Monica F. Chen, MD, medicine resident, and their colleagues, reviewed cancer patients who were tested for COVID-19 between March 1, 2020, and June 6, 2020, at NewYork-Presbyterian/Columbia University Irving Medical Center. Of the 1,174 tested, 317 patients were positive. Approximately 27 percent had a recent cancer diagnosis; 56.7 percent had active disease; and 56.7 percent had been on active cancer treatment within the past year.
“We found that patients on active treatment, including chemotherapy, were not at increased risk for COVID-19, and surprisingly, they were less likely to test positive for COVID-19 than those not on treatment,” says Dr. Chen. The researchers also noted that the factors associated with COVID-19 in the general population – older age, minority race/ethnicity, and obesity – were consistent among patients with cancer.
Compared with cancer patients not receiving any treatment at the time of the study, those receiving chemotherapy were 35 percent less likely to develop COVID-19. This was possibly due to greater vigilance with social distancing, wearing face masks, and hand hygiene than those in remission, potentially resulting in fewer infections. “These findings may be reassuring to cancer patients that are on active treatment,” says Dr. Crew, “and perhaps this will lead to less disruptions in cancer care.”
The Columbia researchers presented their findings at the American Association for Cancer Research Virtual Meeting: Covid-19 and Cancer in February 2021.
Patients on Active Chemotherapy May Not Be at Increased Risk for COVID-19 Infection. The ASCO Post, February 5, 2021.
Impact of SARS-CoV-2 on Patients Receiving Cancer Therapy
What is the duration and impact of SARS-CoV-2 on patients who have both cancer and mild-to-moderate COVID-19 undergoing cancer-directed therapy, especially in the underserved population?
This is the question that Columbia University faculty in the Division of Hematology and Oncology sought to answer through a retrospective study of 299 patients with cancer who were tested for COVID-19 at NewYork-Presbyterian/Columbia University Irving Medical Center, a Minority-NCI Community Oncology site. Of these patients, 77 tested positive for COVID-19. Additionally, they retrospectively analyzed 26 patients with mild-to-moderate COVID-19 receiving cancer therapy who consented to undergo PCR testing every one to two weeks. Testing continued until two successive negative PCRs were obtained prior to restarting their cancer therapy.
The Columbia University researchers noted that patients receiving cancer therapy appear to have prolonged detectable SARS-CoV-2, which can lead to interruption of treatment and progression of disease. The authors conclude that patients with active aggressive malignancies who are diagnosed with mild to asymptomatic COVID-19 should continue on therapy without pause given the increased risk of cancer-related morbidity and mortality. They also recommend that these patients be monitored closely while on treatment to assess for worsening SARS-CoV-2 infection.
Wong W, Brieva C, May M, Gambina K, Whittier S, Hod EA, Pellicciotta I, Pan S, Hu J, Abbott M, Schwartz GK, Manji GA. A double-edged sword: Prolonged detection of SARS-COV-2 in patients receiving cancer-directed therapy. Seminars in Oncology. 2020 Dec 5:S0093-7754(20)30121-4.
COVID-19 Severity and Cancer Outcomes
Patients with cancer may be particularly vulnerable to COVID-19 due to their immunocompromised state from the underlying cancer and the sequalae of therapy. At Weill Cornell Medicine, researchers note it is important to weigh the risk of severe COVID-19 illness against the risk of delaying cancer treatment.
To better understand these risks, the Weill Cornell Medicine research team evaluated the morbidity and mortality of hospitalized cancer patients with COVID-19 and compared them to a matched cohort of patients without cancer. The study evaluated 585 patients who were COVID-19 positive; 117 had active malignancy. Their findings showed that both cancer and non-cancer groups of patients had similar outcomes to other patients with COVID-19. Published in the Journal of Clinical Oncology in November 2020, the study suggests that in the absence of other risk factors for poor COVID-19 outcomes, cancer patients may be able to safely continue treatment.
“Our findings suggest that if you have cancer and you’re relatively young and with no other major illnesses, then your risk of having a severe outcome if you get COVID-19 is not as high as you might expect – so perhaps you can be more confident in continuing your chemotherapy,” says senior author Manish A. Shah, MD, Director of Gastrointestinal Oncology and a member of the Weill Cornell Medicine Meyer Cancer Center.
Although there is no conclusive evidence that cancer patients are more easily infected than others, the immune suppression caused by many cancer treatments could enhance infection risk, even if it doesn’t lead to worse outcomes after infection.
Brar G, Pinheiro LC, Shusterman M, Swed B, Reshetnyak E, Soroka O, Chen F, Yamshon S, Vaughn J, Martin P, Paul D, Hidalgo M, Shah MA. COVID-19 Severity and Outcomes in Patients With Cancer: A Matched Cohort Study. Journal of Clinical Oncology. 2020 Nov 20;38(33):3914-3924.
Developing a Lung Atlas to Better Understand Long-Term Complications of COVID-19
Oncologists and other medical and scientific faculty at Columbia University, Weill Cornell Medicine, and centers in the Northeast and California, came together with a mission to decipher host responses to lethal SARS-CoV-2 infection. Their collaboration led to the development of a single-cell transcriptome lung atlas of COVID-19 that helps to inform the understanding of long-term complications of survivors and provides an important resource for therapeutic development.
The group of more than 40 investigators led by Benjamin Izar, MD, PhD, Assistant Professor of Medicine, Columbia University Vagelos College of Physicians and Surgeons, performed single-nucleus RNA sequencing of approximately 116,000 nuclei from the lungs of 19 individuals who died of COVID-19. The autopsy specimens were taken at a short post-mortem interval and compared to control lung samples. The analysis afforded a broad census of the cellular landscape and cell programs and also identified pathological circuits of lethal COVID-19. The data suggest that despite a potentially sufficient humoral immune response, there was an inadequate T cell response in the lungs of individuals who died of COVID-19.
The research team reports that a recent study by Bange, E.M. et al showed that “impaired B cell function in patients with cancer who contracted COVID-19 was not associated with increased mortality, but that lack of an adequate CD8+ T cell response (even in the presence of adequate humoral immunity) was associated with worse viral control and increased mortality.” Although the COVID-19 cohort in the current study did not include patients with cancer, these data suggest that whereas humoral immunity may be dispensable in the context of adequate T cell immunity against SARS-CoV-2, a lack of appropriate T cell responses likely contributed to fatal outcomes.
The study provides insight into host responses to lethal SARS-CoV-2 infection, with the researchers also noting several observations, including the rapid development of pulmonary fibrosis, which may be pertinent for patients who survive severe COVID-19. In addition to serving as a clinical resource, the atlas offers an important reservoir of material for investigations into host responses to SARS-CoV-2 and understanding of its potential long-term pulmonary sequelae.
“It’s a devastating disease, but the picture we’re getting of the COVID-19 lung is the first step towards identifying potential targets and therapies that disrupt some of the disease’s vicious circuits,” says Dr. Izar. “In particular, targeting cells responsible for pulmonary fibrosis early on could possibly prevent or ameliorate long-term complications in survivors of severe COVID-19.”
Melms JC, Biermann J, Huang H, Wang Y, Nair A, Tagore S, Katsyv I, Rendeiro AF, Amin AD, Schapiro D, Frangieh CJ, Luoma AM, Filliol A, Fang Y, Ravichandran H, Clausi MG, Alba GA, Rogava M, Chen SW, Ho P, Montoro DT, Kornberg AE, Han AS, Bakhoum MF, Anandasabapathy N, Suárez-Fariñas M, Bakhoum SF, Bram Y, Borczuk A, Guo XV, Lefkowitch JH, Marboe C, Lagana SM, Del Portillo A, Zorn E, Markowitz GS, Schwabe RF, Schwartz RE, Elemento O, Saqi A, Hibshoosh H, Que J, Izar B. A molecular single-cell lung atlas of lethal COVID-19. Nature. 2021 Jul;595(7865):114-119.