COVID-19 in patients with lung cancer

Abstract

Background: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic.

Patients and methods: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166).

Results: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes.

Conclusion: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

Keywords: COVID-19; chemotherapy; immunotherapy/checkpoint blockade; lung cancer; small molecule agents.

Figure 1

COVID-19 in patients with lung cancers. (A) Estimated percent of COVID-19-related deaths that occurred during the study period among all deaths of patients with lung cancers shown as a 7-day rolling average (green line). The first positive SARS-CoV-2 test in a patient with lung cancer occurred on 12 March 2020. (B) Kaplan–Meier estimated survival probability starting from date of positive SARS-CoV-2-positive swab. Confidence band represents the 95% confidence interval (CI). (C) Presenting signs and symptoms of COVID-19 infection in patients with known information for these symptoms (n = 89). Figure shows both single and clusters of signs and symptoms. Vertical bars and corresponding heatmap represents frequency of sign and symptom clusters that occurred >4%. (D) Patients were identified starting from the first case on 12 March 2020 through 6 May 2020, and followed until 11 May 2020. Median follow up was 25 days (IQR 10–36 days). Symptom presentation, hospitalization status, highest level of care, and patient COVID-19 status at time of last follow up. Vertical bar graph represents the cumulative number of symptomatic patients (98%, n = 85/87; 87 had a known symptom start date) leading up to the date of the positive SARS-CoV-2 swab. ∗percentages may add up to greater than 100% due to rounding. COVID-19, coronavirus disease 2019; GI, gastrointestinal; ICU, intensive care unit; IQR, interquartile range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. ^a Percentages may add up to >100% due to rounding.

Figure 2

Impact of cancer-specific and additional laboratory features on severity of COVID-19 in lung cancer. (A) Odds ratios (ORs) for the impact of baseline characteristics of patients on severity outcomes associated with COVID-19 [rate of hospitalization; ICU admission, intubation, and/or change to DNI status to avoid intensification of care (e.g. intubation) (ICU/intubation/DNI); or death]. ORs were calculated using univariate logistic regression. Error bars represent 95% CIs. The x-axis is on a log₁₀ scale. For the continuous variables: ORs for age compare an older person and younger person with an age difference of 10 years; ORs for pack-years smoked compare median smoking (23.5 pack-years) to never smoking (0 pack-years); ORs for body mass index (BMI) compare a person with higher BMI to lower BMI with a difference of 5 kg/m². (B) Among hospitalized patients, showing ORs for the impact of symptoms at presentation with lung cancers and COVID-19 on severity outcomes (ICU/intubation/DNI and death). ORs were calculated using univariate logistic regression. Error bars represent 95% CIs. The x-axis is on a log₁₀ scale. (C) Among hospitalized patients, baseline creatinine and inflammatory markers (D-dimer, ferritin, interleukin-6) of patients who experienced severe COVID-19 outcomes (ICU/intubation/DNI and death). Dots represent individual values. Dashed lines within violins represent median, 25% percentile, and 75% percentile. Violins show min-max ranges and kernel density estimate distributions of each group. Gray dashed lines represent the normal range for that laboratory value. The Mann–Whitney U test was used for calculating P values. (D) The frequency of imputed HLA-A and HLA-B alleles among control, mild, and severe patients with lung cancers and COVID-19. CI, confidence interval; COVID-19, coronavirus disease 2019; DNI, do not intubate; DVT, deep venous thrombosis; GI, gastrointestinal; HLA, human leukocyte antigen; ICU, intensive care unit; IQR, interquartile range; PE, pulmonary embolism. ^ametastatic or active lung cancer was defined as patients with metastatic lung cancer or patients undergoing active treatment for lung cancer (e.g. neoadjuvant or adjuvant therapy); ^bCOPD was defined as anyone with this diagnosis listed as a part of the past medical history plus either an abnormal pulmonary function test interpreted as consistent with COPD or had inhalers for COPD listed in the outpatient medication record. Patients with only radiologic evidence of COPD or a note in the medical record the diagnosis was in question were not included; ^cNon-COPD lung disease was defined as underlying lung disease other than COPD (eg reactive airways disease, pneumonitis, abnormal pulmonary function test interpreted as underlying lung disease, etc.); ^dCongestive heart failure was defined as anyone with NYHA functional class I-IV disease. As such, anyone with this diagnosis listed as a part of the past medical history or an abnormal cardiac echocardiogram demonstrating evidence of structural heart disease consistent with this diagnosis was included.

Figure 3

Impact of cancer therapy on COVID-19 severity in patients with lung cancers. For each figure in this series, the % of all patients (n = 102) who received various cancer therapy regimens during the time period defined before the swab date. Dots show (left) the rate of hospitalization (middle) ICU admission, intubation, and/or change to DNI status to avoid intensification of care (e.g. intubation) (right) or death among patients with COVID-19 with known status of the outcome displayed. The four treatment categories of interest included (A) prior PD-1 blockade within 6 weeks of swab, (B) prior PD-1 blockade and chemotherapy within 3 weeks of swab, (C) prior chemotherapy within 3 weeks of swab, and (D) prior tyrosine kinase inhibitor (TKI) within 1 week of swab. There was no significant difference in severity outcomes in any of the comparisons. Error bars represent 95% confidence intervals. chemo, chemotherapy; COVID-19, coronavirus disease 2019; DNI, do not intubate; ICU, intensive care unit; PD-1, programmed cell death protein 1.

Figure 4

Recovery from COVID-19 in patients with lung cancers. (A) Cumulative probability of recovery by highest level of care: outpatient (n = 39), non-ICU hospital floor (n = 41), and ICU (n = 21). Recovered was defined as a combination of at least 14 days from positive swab date and asymptomatic for 72 h. Two patients among patients categorized as ‘non-ICU hospital floor’ were residing in an inpatient facility at the time of diagnosis of COVID-19. (B) Rate of baseline characteristics among patients who are either improving or recovered from COVID-19 (n = 66) compared with died (n = 25). Patients with pending clinical status were not included (n = 11). Significant odds ratios are denoted by asterisks. Fewer pack-years smoked, continuous (OR 0.45, 95% CI 0.18–0.93); absence of COPD (OR 0.31, 95% CI 0.90–0.12); absence of congestive heart failure (OR 0.05, 95% CI 0.004–0.35). Percent of cases or median (interquartile range) are below each bar. Error bars represent 95% CIs. (C) ORs for the impact of inpatient hydroxychloroquine use for COVID-19 on severity outcomes associated with COVID-19 (ICU/intubation/DNI and death). ORs were calculated using univariate logistic regression. Error bars represent 95% CIs. The x-axis is on a log₁₀ scale. CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; DNI, do not intubate; DVT, deep venous thrombosis; ICU, intensive care unit; OR, odds ratio; PE, pulmonary embolism.