Severity of COVID-19 in Patients with Lung Cancer: Not Driven by Cancer or Cancer Treatments

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COVID-19 was severe in patients with lung cancer, but deaths were mainly related to patient-specific features, not cancer-specific features or treatments, according to our retrospective study of 102 patients with lung cancer and COVID-19 diagnoses at Memorial Sloan Kettering Cancer Center (MSK) from March through May 2020. (1)

Our study, published recently in the Annals of Oncology, suggests that the greatest determinants of COVID-19 severity were patient features and comorbidities, such as a history of heavy smoking and chronic obstructive pulmonary disease (COPD). Cancer-specific features, including prior thoracic surgery or radiation and recent systemic therapies, did not clearly impact COVID-19 severity. (1)

Among the 102 patients with lung cancer and confirmed COVID-19, 62 percent were hospitalized, and 25 percent died. Overall, COVID-19 accounted for a small fraction (11 percent) of deaths that occurred among patients with lung cancers during the study. (1)

We found that HLA-A and HLA-B supertypes were generally similar in mild or severe cases of COVID-19 compared to lung cancer patients without COVID-19. However, future studies with larger sample sizes will be required to understand precisely how HLA alleles modify COVID-19 severity. (1)

Finally, hydroxychloroquine did not improve COVID-19 outcomes among hospitalized patients, (1) consistent with a retrospective study published recently in the New England Journal of Medicine (2) and a randomized controlled study in China. (3)

Overall, our findings amplify the importance of focusing on the needs of cancer patients and optimizing their care as infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to spread in local communities.

COVID-19 and Lung Cancer

Multiple studies have reported that patients with cancers, particularly lung cancers, experience disproportionately severe illness and deaths from COVID-19. (4)(5)(6)(7) We previously explored the impact of PD-1 blockade therapy on COVID-19 severity in patients with lung cancers and did not find a clinically meaningful association. (8)

Our present study examined whether lung cancer itself or other pre-existing factors, such as age, smoking history, genetic variation in immunity, underlying cardiopulmonary disease, and/or cancer treatments predispose individuals to more severe illness from SARS-CoV-2 infection.

The rationale behind exploring genetic differences related to the immune response is that class I HLA alleles play a role in determining the quality and quantity of COVID-19 antigens presented for the adaptive immune response, which may alter the effectiveness of acute and memory T cell responses.

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Study Design

We included 102 patients with lung cancer at MSK who tested positive with a SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test from March 12, 2020, to May 6, 2020, including those who tested positive for COVID-19 at MSK (n=61) or other healthcare facilities (n=41). (1)

Our research team manually reviewed patient records to identify demographics, patient-reported smoking history, baseline clinical characteristics, comorbidities, pathology characteristics, treatments, symptoms, lab results, disease course, and vital status. Baseline lab values included complete blood count, serum creatinine, liver function tests, and inflammatory markers on the day of the COVID-19 test, or the day before or after if same-day information was not available. (1)

Patients were considered to have severe COVID-19 if they had been in intensive care, intubated, needed invasive mechanical ventilation, transitioned to a do not resuscitate order, and/or died. All other patients were classified as having mild COVID-19. (1)

To examine the impact of cancer therapy on the severity of COVID-19, we defined recency of therapeutic doses relative to positive SARS-CoV-2 RT-PCR tests as follows: within six weeks for PD-L1 blockade; within three weeks for chemotherapy; and, within one week for tyrosine kinase inhibitors (TKIs). (1)

To explore whether there was an association between HLA genotype with COVID-19 severity, we identified a subgroup of 46 patients who had MSK-IMPACT next-generation sequencing results. We used the data to infer imputed class HLA-A and HLA-B alleles, and categorized each HLA cohort into 12 supertypes, using anchor residue specificity similarities as previously defined. (9) We classified HLA types that did not fit into these supertype categories as “Other A, B.” (1)

Control HLA-A and HLA-B data were available for 5,166 patients with lung cancers and no known diagnosis of COVID-19. We categorized the control group’s HLA-A and HLA-B data into the same supertypes to establish a null distribution and to allow us to look for differences between mild and severe COVID-19 cohorts compared to a control group.

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Study Findings

The median age was 68 years old, ranging from 31 to 91 years. Most patients, 73 percent had active or metastatic lung cancer, and the median pack-year smoking history was 23.5 (range 0 to 120 pack-years). The most common chronic conditions were hypertension (56 percent) and COPD (24 percent). (1)

Patients who died from confirmed COVID-19 during our study period represented 11 percent of all deaths among patients with lung cancers at our center. Deaths related to COVID-19 peaked at about 20 percent in April 2020, and most deaths occurred within a week of COVID-19 diagnosis. Although cough and fever were the most common symptoms, patients had a constellation of symptoms that varied. (1)

Among 102 patients, 62 percent required hospitalization and 25 percent died. Of the 21 percent of patients who needed intensive care, 14 percent recovered, and 72 percent died. (1)

We found several baseline clinical features that were consistently associated with an increased risk of COVID-19 severity, including age, smoking history, COPD, and hypertension. Congestive heart failure was also associated with increased COVID-19 severity, albeit in a small number of patients (n=7). (1)

Cancer-specific features, such as having active or metastatic cancer, a history of prior thoracic radiation or surgery, presence of targetable oncogenes, or PD-L1 immunohistochemistry, did not impact COVID-19 severity. Recent cancer therapy, including PD-1 blockade, with or without chemotherapy, did not associate with increased COVID-19 severity. We also did not observe a consistent impact on severity with chemotherapy or TKIs. (1)

The need for supplemental oxygen at presentation was associated with a nine-fold greater risk of severe COVID-19 illness (OR 9.0, 95% CI: 2.31–28.44), intensive care admission, intubation, and/or revision to DNI status, and a four-fold greater risk of death (OR 4.21, 95% CI: 0.99–15.25). (1)

Although severe COVID-19 illness rates were elevated in patients with lung cancers, a majority of them, 65 percent, recovered or were improving on writing our paper. The median time to recovery for outpatients, patients requiring non-ICU hospitalization, and patients needing ICU care was 18 days, 34 days, and not reached, respectively. Among 18 patients who required ICU care, five who required intubation have since been extubated, and three have been discharged home or to a rehabilitation facility. (1)

Less smoking history (OR 0.45, 95% CI: 0.18–0.93), absence of COPD (OR 0.31, 95% CI: 0.90–0.12), and absence of congestive heart failure (OR 0.05, 95% CI: 0.004–0.35) were associated with better odds of recovery. (1)

Treatment with hydroxychloroquine (73 percent, 35 of 48 patients) was not associated with improved outcomes (OR for ICU/intubation/DNI 1.39, 95% CI: 0.37–4.56, p=0.7) and (OR for death 1.03, 95% CI: 0.26–3.55, p=0.99). (1)

Note that given the sample size of our study, we were not able to perform adjustments for multiple potential confounders with smaller effect sizes. Larger studies with bigger cohorts are needed to confirm our results.

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Advancing Cancer Care During the COVID-19 Pandemic

At MSK, our researchers and clinicians are an essential part of the international response to the COVID-19 pandemic. Our present study about the severity of COVID-19 in lung cancer patients was a collaborative effort by 31 investigators.

We continue to collaborate to deliver excellent, evidence-based care for our patients. Read more about our recently published research about cancer and COVID-19:

MSK is offering a twice-weekly scientific seminar series called MSK Science Spotlight, featuring lectures by leaders in basic and translational biomedical science. Seminars are available via livestream every Monday and Wednesday at 4:30 p.m. ET. Seminars last 60 minutes, including 15 minutes for Q & A. No registration is required. Check out the schedule or watch past seminars here.

The study was supported by grants from the MSK Support Grant/Core, the Druckenmiller Center for Lung Cancer Research at MSK; the National Institutes of Health, the Damon Runyon Cancer Research Foundation, Stand Up To Cancer, the Entertainment Industry Foundation, the Society for Immunotherapy of Cancer, the Lustgarten Foundation, and The Mark Foundation for Cancer Research.

Dr. Hellmann is a member of the Parker Institute for Cancer Immunotherapy. He receives institutional research funding from Bristol-Myers Squibb; has been a compensated consultant for Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Nektar, Syndax, Mirati, Shattuck Labs, Immunai, Blueprint Medicines, Achilles, and Arcus; received travel support/honoraria from AstraZeneca, Eli Lilly, and Bristol-Myers Squibb; has options from Shattuck Labs, Immunai, and Arcus; has a patent filed by his institution related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. For disclosures from other study authors, please refer to the paper. (1)

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  1. Luo J, Rizvi H, Preeshagul IR, et al. COVID-19 in patients with lung cancer [published online ahead of print, 2020 Jun 16]. Ann Oncol. 2020;S0923-7534(20)39894-X.
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