Characteristics and outcome of lung cancer patients and Covid-19 infection in a second-level hospital during the first 3 months of the pandemic

Dear Editor,

On 31 January 2020, the new SARS-CoV-2 coronavirus touched Spanish turf for the first time. It was not until the beginning of March when intra-community transmission was detected, transforming it into a major public health problem and causing an unprecedented health alert. During this period, cancer patients and those with serious chronic diseases were the only ones who continued to received their usual healthcare. For this reason, together with their status of immunosuppression, it seems they have had a higher incidence of Covid-19, as we have seen in different case series from China.^1–3 Furthermore, we ourselves have observed a higher cumulative incidence of cases among the general cancer population in our centre during the first month of the pandemic,⁴ with an increase in mortality,^1–4 which was even higher in patients with lung cancer, as shown in the TERAVOLT study.⁵

Our study is a retrospective study, describing the characteristics and progression of lung cancer patients who developed Covid-19, between 5 March and 2 June 2020. Additionally, we observe whether there is higher mortality among patients with lung cancer compared to the general reference population of our centre.

Twenty-four lung cancer patients were diagnosed with Covid-19. The median age was 70 years (range 49–84), mostly males (n = 16, 66.7%). The most common subtype of lung cancer was non-small cell carcinoma (n = 21, 87.5%), with the majority presenting metastatic disease (n = 14, 58.3%). Sixteen patients (66.7%) had arterial hypertension, 13 (54.2%) had chronic obstructive pulmonary disease (COPD). Twenty patients required admission (83.3%), with a total of 10 patients who presented bilateral pneumonia (41.7%) and 5 cases (20.8%) developed acute respiratory distress syndrome (ARDS). No patient was admitted to the ICU. The median haemoglobin was 11.65 g/dL (range 7.2–15 g/dL), median lymphocytes 800 10³/μL (range 200–2400 10³/μL), median d-dimer 1520 μg/L (320–10,430 μg/L) and median C-reactive protein (CRP) 53.85 mg/L (range 0.05–151.1 mg/L). Sixteen patients (66.7%) were treated with hydroxychloroquine and azithromycin, compared with 7 (29.2%) who received lopinavir/ritonavir. Two patients also received tocilizumab (8.3%) and nine (37.5%) received steroid boluses (Table 1).

Table 1.

Clinical and demographic parameters in deceased and surviving patients with lung cancer and Covid-19.

	Survivors (n = 12)	Deceased patients (n = 12)	p
Age, median	67.5	72	0.23
Male gender,n(%)	7 (58.3)	9 (75.0)	0.38
Cancer characteristics
Cancer treatment
Chemotherapy, n (%)	5 (41.7)	2 (16.7)	0.46
Staging
Metastatic disease, n (%)	5 (41.7)	9 (75.0)	0.09
Covid-19 characteristics
Covid-19 treatment
Hydroxychloroquine + azithromycin, n (%)	10 (83.3)	6 (50.0)	0.08
Lopinavir/ritonavir, n (%)	2 (16.7)	5 (41.7)	0.17
Symptoms of Covid-19
Dyspnoea, n (%)	10 (83.3)	12 (100)	0.14
Bilateral pneumonia, n (%)	4 (33.3)	6 (50.0)	0.07
Analytical characteristics
Haemoglobin (g/dL), median	11.6	11.9	0.32
Lymphocytes (10^3/μL), median	1000	700	0.39
Neutrophil/lymphocyte ratio > 5, n (%)	4 (33)	8 (66.7)	0.18
d-Dimer (μg/L), median	655	2.300	0.23
LDH (U/L), median	291	433	0.26
CRP (mg/L), median	37.0	56.1	0.66
Comorbidities
Arterial hypertension, n (%)	6 (50.0)	10 (83.3)	0.08
COPD, n (%)	7 (58.3)	6 (50.0)	0.68
CKD, n (%)	2 (16.7)	1 (8.3)	0.53
Heart disease, n (%)	2 (16.7)	4 (33.3)	0.34

COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; LDH: lactate dehydrogenase; CRP: C-reactive protein.

Regarding mortality, 12 patients (50.0%) died of Covid-19, without their oncological disease having influenced this process, compared to 302 of 2266 (13.32%) of the total affected by Covid-19 in our centre (p > 0.00001). We observed a trend towards significance with increased mortality in patients with metastatic disease (9/14 vs. 3/10 in non-metastatic patients, p = 0.09), and the same in patients with arterial hypertension (10/16 deaths vs. 2/8 in non-hypertensive patients, p = 0.08) and in those who developed ARDS (4/5 deaths vs. 8/19 deaths in patients who did not present it, p = 0.11). There is a tendency towards a reduction in mortality of patients treated with hydroxychloroquine and azithromycin (only 6/16 died vs. 6/8 with other treatments, p = 0.08), and this significance is maintained in the multivariate logistic regression (OR 0.12 [CI 95% 0.01–1.4], p = 0.09) regardless of comorbidities, presence of metastasis and ARDS. This was not the case with patients receiving lopinavir/ritonavir (5/7 deaths).

In our study, we found a greater risk of mortality in diagnosed lung cancer patients with Covid-19. It was much higher than that of our general population, mainly in metastatic disease and hypertensive patients, probably due to the underlying pathology and the immunosuppression status.

Two Chinese case series also describe an increase in mortality compared to the general population, with a mortality rate of 39% and 28.6%, however the sample size was small and the tumour samples were heterogeneous, with the majority of the patients not presenting metastatic disease and therefore having a better prognosis compared to our series.^2,3 In the TERAVOLT study,⁵ which was methodologically similar to ours, 33.3% mortality was described, but no associated risk factor was able to be identified. In our study, it should probably be taken into account that no patient was admitted to the ICU, influencing the result.

Additionally, we have observed a trend towards a reduction in mortality in those patients treated with hydroxychloroquine and azithromycin. However, the limitations of our study namely being retrospective and the small number of patients must be recognised.

In conclusion, cancer patients with advanced thoracic tumours have a higher risk of mortality from Covid-19. Therefore, the development of clinical practice guidelines or recommendations for the management of these two pathologies is obligatory.

Authorship

The first two authors contributed equally to the development of the manuscript: JR and GSM contributed to the study conception and design, data acquisition, statistical analysis, data interpretation and writing of the manuscript. CP contributed to the study conception and design, data interpretation and writing of the manuscript. All authors reviewed and approved the final version of the manuscript.