COVID-19 in Belgium, at CUSL, and in the health care workers of the CUSL ambulatory cancer care unit.
Table 1 summarizes the COVID-19 pandemic epidemiology in Belgium and the main actions our cancer center implemented according to national and institutional recommendations. Belgian official COVID-19 data are continuously updated on https://covid-19.sciensano.be. Between February 15 and July 13, 2020, only two (7%) out of the 28 physicians who attended the outpatient cancer center daily developed a symptomatic COVID-19 infection documented by SARS-CoV-2 RT-PCR. None of the other physicians nor the unit’s 19 oncological nurses developed a symptomatic infection. All healthcare workers were tested for SARS-CoV-2 antibodies during the same period as the ONCOSARS-1 study. Only the two physicians who were positive for SARS-CoV-2 by RT-PCR developed antibodies against SARS-CoV-2.
Patient characteristics and incidence of SARS-CoV-2 detection
Of the 415 patients admitted to our oncology day unit between June 12 and July 13, 2020, 379 (91%) signed the informed consent and 363 (87%) met our inclusion criteria (Figure 1). Table 2 outlines the main patient characteristics. Per the inclusion criteria, all eligible patients (n=363) had SARS-CoV-2 serology performed. Among these, 141 (38.8%) underwent RT-PCR during the COVID-19 pandemic: 22 (16%) had symptoms suggestive of a SARS-CoV-2 infection that triggered the test and 119 (84%) were tested as part of a systematic screening plan. This plan, introduced by CUSL, from April 1, 2020, mandated that all patients planned for a medical procedure or overnight stay must undergo systematic screening with SARS-CoV-2 RT-PCR (Table 1). However, this systematic screening was not implemented in the outpatient oncology day unit, mainly due to logistical reasons.
According to RT-PCR or serological test, 22 (6%) of the 363 eligible patients had been exposed to SARS-CoV-2. Seventeen (5%) of the 363 patients had detectable antibodies against SARS-CoV-2. Fourteen (10%) of the 141 patients tested for SARS-CoV-2 by RT-PCR were positive. For RT-PCR, the positivity rate varied largely between symptomatic and systematically screened patients: 9 out of 22 (41%) versus 5 out of 119 (4%), respectively (odds ratio (OR) 15.8, P<0.001). SARS-CoV-2 seroconversion was detected in 9 (64%) of the RT-PCR-positive patients (Table S1).
Three hundred and forty-nine patients did not undergo any RT-PCR test or had a negative RT-PCR test (Table S2). Eight (2%) of these patients developed antibodies against SARS-CoV-2. Five of these eight had undergone an RT-PCR test, but none experienced COVID-19 symptoms.
SARS-CoV-2-positive patients diagnosed either by RT-PCR or serological test (n=22) did not statistically differ from SARS-CoV-2-negative patients (n=341) with regards to potential risk factors for severe COVID-19 disease (age, comorbidities, smoking, lung cancer, advanced disease, number of lines of systemic therapies for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status) (Table 2) . However, the SARS-CoV-2-negative patients had received overall more immunotherapy, generating an imbalance between the treatment groups (P=0.029). In terms of cancer types, head and neck cancers and skin cancers were only observed in the SARS-CoV-2 negative group. SARS-CoV-2-positive patients received more thoracic radiotherapy over the previous six months (P=0.007). These same trends were also seen numerically in the COVID-19 subgroups detected through RT-PCR alone (Table S1) or serology alone (Table S2).
COVID-19 symptoms and thoracic imaging
Among the 363 patients, 150 (41%) developed symptoms suggestive of COVID-19 infection and 213 (59%) remained asymptomatic. Although present in only 5 (23%) SARS-CoV-2-positive patients, anosmia appeared to be the most discriminant symptom with no anosmia reported in the SARS-CoV-2-negative patients (P < 0.001). Dyspnea and rhinitis were not discriminant, being frequently reported in treated cancer patients. SARS-CoV-2-positive patients presented at least one of the more specific COVID-19 symptoms (fever or cough or anosmia) more frequently during the follow-up period (46% vs 13%, P < 0.001) (Table 2). Similar findings were observed for the population described in the COVID-19 subgroups detected through RT-PCR alone (Table S1) or serology alone (Table S2).
Overall, 280 (77%) patients underwent a thoracic computed tomography (CT) scan or a 2′-deoxy-2′-[18F] fluoro-D-glucose positron emission tomography (18-FDG-PET) coupled with a thoracic CT scan during the follow-up period, representing 64% and 78% of the SARS-CoV-2-positive and -negative patients, respectively (P=0.123) (Table 2). These images were pre-planned to evaluate treatment efficacy in 97% of patients. Radiologic signs potentially related to COVID-19  were more frequent in the SARS-CoV-2-positive patients (37% versus 7%, P < 0.001). Analyses of the subgroups of patients diagnosed by SARS-CoV-2 RT-PCR alone or by serology alone revealed the same trend (Table S1 and S2). Eight (89%) out of nine patients with a positive SARS-CoV-2 RT-PCR with subsequent seroconversion presented COVID-19 symptoms and/or suggestive CT scan findings. In contrast, only one (20%) out of five patients with a positive SARS-CoV-2 RT-PCR but a negative serological test presented symptoms and/or suggestive CT scan findings (P=0.023).
Adverse events reported during systemic oncological treatments
SARS-CoV-2-positive patients identified either by RT-PCR or serology (n=22) presented more hematological adverse events compared to SARS-CoV-2-negative patients (n=341) (73% vs 35%, P < 0.001). Adverse events for neutropenia and lymphopenia were of all grades (Table 3). Only grade 1-2 thrombopenia was observed. There were no significant differences between the SARS-CoV-2-positive and -negative patients with regards to other observed adverse events. Bleeding, infections unrelated to COVID-19, and febrile neutropenia occurred at a low rate in the SARS-CoV-2 positive patients (Table 3). Both subgroups of COVID-19 detected only through RT-PCR (Table S3) or only through serology (Table S4) presented similar results. In both univariate and multivariate analyses, SARS-CoV-2 positivity, a lower performance status (ECOG 2-3), and treatment with chemotherapy were significantly associated with hematological toxicity. Advanced disease, higher age, the presence of a comorbidity, and symptoms of COVID-19, were not (Table 4).
SARS-CoV-2-positive patients experienced more frequent treatment delays than SARS-CoV-2-negative patients: 55% vs 20%, respectively (P < 0.001). However, the length of delay did not differ between the two groups: median 14 vs 11 days, respectively (P= 0.504). The relationship between treatment delays and hematological adverse events was significant (P < 0.001, Fisher exact test).
Two SARS-CoV-2-positive patients, detected by RT-PCR and later confirmed by serology, prematurely ended their ongoing systemic treatment during the study period; one developed complicated sigmoid diverticulitis, while the second developed grade 2 peripheral neuropathy. Three SARS-CoV-2-negative patients also stopped treatment prematurely; two due to adverse events and one to disease progression. No patients stopped treatment due to the pandemic.
Factors associated with seroconversion
To further assess the factors associated with positive SARS-CoV-2 serology, univariate and multivariate analyses were performed (Table 5). SARS-CoV-2 positivity by RT-PCR was the strongest factor associated with seropositivity. The main COVID-related symptoms (fever, cough or anosmia), or a thoracic CT scan with lung infiltrates suggestive of COVID-19 infection, were also significantly associated with seroconversion in both the univariate and multivariate analyses. A higher age, the presence of a comorbidity, lung cancer, recent morbid surgery, or advanced disease were not associated with seroconversion. Recent thoracic radiotherapy was significantly associated with positive serology in the univariate analysis but not in the multivariate analysis.
Five of the 22 (23%) SARS-CoV-2-positive patients were hospitalized due to COVID-19 infection. Of these, three required transient nasal oxygen therapy. All developed antibodies against SARS-CoV-2. Four additional patients were hospitalized with presumed COVID-19, but their status was validated neither by RT-PCR nor by thoracic imaging. These four patients eventually had negative serology.