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Page 2 of 8 Kulkarni et al. J Cancer Metastasis Treat 2021;7:31 https://dx.doi.org/10.20517/2394-4722.2021.36

INTRODUCTION
Lung cancer is the leading cause of cancer-related death worldwide with approximately 136,000 deaths
[1]
estimated in 2020 in the Unites States alone . Coronavirus disease-2019 (COVID-19) is a respiratory tract
infection caused by the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV2)
that has quickly escalated into a global pandemic after initial outbreak in Wuhan province, China in
December 2019. The United States was the epicenter of the outbreak, with more than 25 million people
[2]
testing positive for COVID-19 and more than 400,000 deaths attributed to COVID-19 as of January 2021 .
COVID-19 severity can range widely from an asymptomatic or mild flu-like illness to respiratory failure and
severe acute respiratory distress syndrome. Large cohort studies have shown that clinical factors consistently
associated with increased risk of death from COVID-19 include older age, male sex, and comorbidities such
as hypertension, diabetes, obesity, and cancer . Biomarkers associated with poor outcomes include
[3,4]
lymphocytopenia, elevated D-Dimer, elevated C-reactive protein, elevated cardiac troponin and elevated
interleukin-6 . Patients with cancer are highly vulnerable to COVID-19 due to their
[5,6]
immunocompromised state, frequent contact with the health care system, advanced age and comorbidities,
putting them in the highest-risk category for COVID-19-related morbidity and mortality. During the early
phase of the pandemic, there were limited data on the impact of COVID-19 in patients with cancer. Recent
studies have consistently shown increased rates of hospitalization, higher COVID-19-related mortality and
higher all-cause mortality in patients with cancer [7-15] . In published studies, the mortality of cancer patients
with COVID-19 can range from 16% to as high as 40% [7-15] . While patients with cancer clearly have worse
outcomes from COVID-19, data on patients with lung cancer and COVID-19 are limited. Available data
suggest that patients with lung cancer may be at a higher risk of severe COVID-19 infection due to
compromised lung function from smoking and chronic-obstructive pulmonary disorder (COPD) [11,16] . In
addition, patients with lung cancer often have symptoms that overlap with COVID-19, potentially causing a
delay in diagnosis. Furthermore, radiographic findings of COVID-19 may be difficult to distinguish from
pneumonitis caused by immunotherapy, radiation, or targeted therapies for lung cancer. In this article, we
provide a comprehensive review of the literature related to COVID-19 and cancer and report data specific
for COVID-19 mortality in patients with lung cancer.

EVIDENCE FROM LARGE COVID-19 AND CANCER COHORT STUDIES - FOCUSING ON
LUNG CANCER
Early reports from China showed a higher burden of COVID-19 in patients with cancer but were limited
[17]
by sample size, short follow-up time and lack of information on cancer status and cancer-specific treatment.
Recently, several large, multi-institutional cohort studies dedicated to cancer patients with COVID-19 have
provided more insights on the risk factors associated with a worse outcome [Table 1]. One of the first large
cohort studies reported was from Wuhan, China which compared 105 patients with COVID-19 and cancer
to 536 age-matched controls without any cancer . In the study, patients with cancer had higher death rates
[9]
[Odds ratio (OR) = 2.34, 95% confidence interval (CI): 1.15-4.77, P = 0.03], higher rates of intensive care
unit (ICU) admission (OR = 2.84, 95%CI: 1.59-5.08, P < 0.01), and higher chances of requiring invasive
mechanical ventilation. The mortality was 11.4% in patients with cancer compared to 4.9% in those without
cancer. In this study, lung cancer was the most prevalent cancer type (20.95%), followed by gastrointestinal
cancer (12.38%) and breast cancer (10.48%). Patients with lung cancer had the second-highest risk for
adverse outcomes; the mortality was 18.1%, the ICU admission rate was 27.2%, and 18.1% required
mechanical ventilation. In another study across 9 hospitals in Hubei province, China, clinical outcomes of
[13]
205 patients with cancer and COVID-19 were reported . The majority of patients had solid tumor
malignancies (89%); breast cancer (20%), colorectal (14%) and lung cancer (12%) were the most common
malignancies. The overall mortality rate was 20% across all cancer types. However, those with lung cancer
had the highest mortality of 25%. Multivariable regression analysis showed that receiving cytotoxic