COVID-19 among lung cancer patients: Data from a real-life prospective French multicentric study.

BACKGROUND: COVID-19 started to spread early in 2020, the precise year that lung cancer (LC) patients were recruited into the prospective epidemiological cohort KBP-2020-CPHG in French hospitals. This provides a unique opportunity to study COVID-19 incidence, survival risk factors, and overall prognosis. METHODS: COVID data was collected before vaccination was made available. Clinical characteristics were compared (COVID vs non-COVID), incidence rate ratios were calculated based on clinical characteristics, survival (1 and 3 months) was estimated and the impact of COVID-19 on the overall prognosis of the cohort was studied. RESULTS: In 2020, 285 out of 8,999 lung cancer patients were diagnosed with COVID-19. Diagnosis was mainly based on PCR tests (86.3 %). The annual incidence was 8.3 % (95 % CI [7.4, 9.3]); it was higher in former smokers and patients with squamous cell carcinoma or small cell carcinoma than in those with adenocarcinoma, in those with a PS score ≥2 versus 0-1, and with stages III-IV versus stages I-II. The incidence was reduced in patients who received chemotherapy or immunotherapy. 64.9 % of patients were hospitalized due to COVID-19. Risk factors for death at 1 and 3 months in COVID-19 patients were age, LC stage, and PS score. Multivariate analysis showed a major prognostic impact of COVID-19 on mortality of LC patients (hazard ratio: 4.12, 95 % CI [3.42, 4.97], p < 0.001). CONCLUSIONS: This prospective study demonstrated the high incidence of COVID-19 in LC patients and identified as risk factors for COVID-19: smoking status, histology, PS, and stage. The impact of COVID-19 on lung cancer mortality appears major.

Evolution of human antibody responses up to one year after SARS-CoV-2 infection

Assessment of the kinetics of SARS-CoV-2 antibodies is essential to predict protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCW) including 393 convalescent COVID-19 and 916 COVID-19 negative HCW up to 405 days. From M1 to M7-9 after infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCW in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N antibodies dramatically decreased (half-life: 210 days) while anti-S stabilized (half-life: 630 days) at a median of 2.41 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.11 -2.75). One case of reinfection was recorded in convalescent HCW (0.47 per 100 person-years) versus 50 in COVID-19 negative HCW (10.11 per 100 person-years). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG [≥] 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached 4 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.

Sex differences in the decline of neutralizing antibodies to SARS-CoV-2

The evolution of SARS-CoV-2 humoral response in infected individuals remains poorly characterized. Here, we performed a longitudinal study of sera from 308 RT-qPCR+ individuals with mild disease, collected at two time-points, up to 6 months post-onset of symptoms (POS). We performed two anti-S and one anti-N serology assays and quantified neutralizing antibodies (NAbs). At month 1 (M1), males, individuals > 50 years of age or with a body mass index (BMI) > 25 exhibited higher levels of antibodies. Antibody levels decreased over time. At M3-6, anti-S antibodies persisted in 99% of individuals while anti-N IgG were measurable in only 59% of individuals. The decline in anti-S and NAbs was faster in males than in females, independently of age and BMI. Our results show that some serology tests are less reliable overtime and suggest that the duration of protection after SARS-CoV-2 infection or vaccination will be different in women and men.

Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France

BackgroundThe serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. MethodsHospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay ([~]99% specificity).The neutralizing activity of the sera was tested with a pseudovirus-based assay. ResultsOf 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P=0.02). ConclusionAntibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

Lung function after lobectomy: a randomized, double-blinded trial comparing thoracic epidural ropivacaine/sufentanil and intravenous morphine for patient-controlled analgesia.

BACKGROUND: Although thoracic epidural analgesia (TEA) is considered superior to IV opioids for postoperative analgesia after thoracic surgery, a few studies clearly demonstrate an improvement in pulmonary function attributable to TEA using a local anesthetic in combination with an opioid. METHODS: In this prospective, randomized, double-blind study, we compared the effects of TEA with ropivacaine and sufentanil (TEA group) to IV morphine (IV group), as they affected pain and pulmonary function after lobectomy in 68 patients. Pain intensity, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flows, and sniff nasal inspiratory pressure as a marker of inspiratory muscle strength were measured from the first to the fourth postoperative day. RESULTS: Pain relief was better in the TEA group at rest and on coughing (P < 0.001). The impairment of FVC and FEV1 was less in the TEA group when compared with that in the IV group (P < 0.001 and P = 0.003, respectively). Sniff nasal inspiratory pressure, FEV1/FVC ratio, and expiratory flow values decreased similarly in both groups. In-hospital mortality, as well as postoperative pulmonary complications, was not different between groups. CONCLUSION: After lobectomy, TEA enables a significant increase in pulmonary function concomitant with better pain relief than systemic morphine, although a modest intercostal motor block may occur.