Decline in Respiratory Functions in Hospitalized SARS-CoV-2 Infected Cancer Patients Following Cytotoxic Chemotherapy-An Additional Risk for Post-chemotherapy Complications

Abstract

Background: Patients recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrate impaired lung function and those requiring chemotherapy after recovering from SARS-CoV-2 infection have yet to be explored. In this study, we sought to investigate the possible pulmonary functional changes during and after administering chemotherapy in patients with prior SARS-CoV-2 infection.

Methods: In this study, a total of 37 SARS-CoV-2 infected patients with cancer who were discharged from hospital and received subsequent cytotoxic chemotherapy were enrolled and prospectively followed-up. The following parameters were prospectively measured before (P1), after first chemotherapy cycle (P2), and 10 weeks after the end of chemotherapy (P3), to assess their impact on respiratory complications in terms of diffusion capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), 6-min walking distance (6MWD) test and levels of key inflammatory markers.

Results: All patients completed at least 2 cycles of chemotherapy without showing overt respiratory complications. Six patients (16%) complained about dyspnea during chemotherapy or at follow-up period. DLCO was significantly impaired during follow-up period [from P1 78 to P3 60% of predicted values; interquartile range (IQR) 55-89] and in 32 of 37 (86% of patients) from P1 to P2 (65% of predictive value; IQR 58-70; p < 0.001). Several patients experienced post-chemotherapy respiratory complications. As expected, all patients from control groups showed persistent improved pulmonary functions.

Conclusion: The risk of pulmonary impairments due to cytotoxic chemotherapy in prior SARS-CoV-2 infected patients is linked to the loss of DLCO. Accordingly, we recommend that for patients with cancer requiring chemotherapy after recovering from prior SARS-CoV-2 infection, pulmonary tests to be performed routinely before and during chemotherapy treatment to monitor the pulmonary performance.

Keywords: DLCO; HRCT (high resolution computed tomography); SARS-CoV-2; cancer; chemotherapy; pulmonary impairment.

Figure 1

Patients recruitment profile. DLCO, lung diffusion for carbon monoxide; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; RV, residual volume; TLC, total lung capacity; 6MWT, 6-minute walking time.

Figure 2

Radiographic features of HRCT images and DLCO measurement from COVID-19 infected cancer patients. (A) Representative images showing ground glass opacity, reticular opacity, subpleural opacity and bronchiectasis of indicated patients. (B) Figure show the changes in lung diffusion for carbon monoxide (DLCO) at each time point. SARS-CoV-2 infected cancer patients treated with chemotherapy before (P1), after first cycle of chemotherapy (P2) and 10 weeks after the end of chemotherapy (P3). P < 0.0001: changes of DLCO from P1 to P2, p = 0.002: Changes of DLCO from P2 to P3. (C) Graph show the change of DLCO of cancer patients treated with chemotherapy 2–6 months before SARS-CoV-2 infection at three time points. Changes of DLCO from P1 to P2, p = 0.02: changes of DLCO from P2 to P3, p = 0.03. Horizontal broken red line indicates the normal cutoff of 80%. (D) Graph show the change of DLCO of non-cancer SARS-CoV-2 infection only patients at three time points. Changes of DLCO from P1 to P2, p < 0.01: changes of DLCO from P2 to P3, p = 0.02. Horizontal broken red line indicates the normal cutoff of 80% predicted. DLCOP1, measurement of DLCO before administering chemotherapy; DLCOP2, measurement of DLCO after first chemotherapy cycle, DLCOP3, measurement of DLCO ten weeks after the end of chemotherapy. Horizontal broken red line indicates the normal cutoff of 80% predicted.

Figure 3

Changes of laboratory features on cancer patients undergoing cytotoxic chemotherapy on prior COVID-19 infected patients. (A–D) Graphs showing the temporal changes in creatinine and inflammatory markers. (A) creatinine, (B) D-dimers, (C) ferritin, and (D) interleukin-6) of cancer patients infected with SARS-CoV-2 and subsequently treated with anti-cancer therapy. Data are median (IQR). Solid lines within violins represents median, 25% percentile, and 75% percentile. Violins show min-max ranges. The Mann-Whitney U test was used for calculating p values. P1, measurement before administering chemotherapy; P2, measurement after first chemotherapy cycle, P3, measurement 10 weeks after the end of chemotherapy.