Humoral and cell-mediated immune response to the third dose of BNT162b2 anti- SARS-CoV-2 vaccine in patients with cancer on active treatment: Focus on wild type, Delta and Omicron strains

Background: Although a full course of COVID-19 vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in cancer patients undergoing active treatment. Methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were prospectively enrolled in this study. Patients were classified in SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Abs) titer and total anti-Spike IgG concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline (T0) and 3 weeks after the booster (T1). Results: 142 consecutive patients were recruited. In SARS-CoV-2 naïve subjects, median level of IgG was 157 BAU/mL (interquartile range (IQR) 62-423) at T0 and reached median of 2080 (IQR 2080-2080) at three weeks after booster administration (T1;p < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Abs titre (IQR 4-32) was observed in naïve subjects (from median 20 IQR 10-40 to median 640 IQR 160-640;p < 0.0001). Median IFN-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV- 2 naïve subjects (p = 0.0049) but not in SARS-CoV-2 experienced patients. No difference was observed in terms of median response between patients treated with immunotherapy and chemotherapy (p > 0.05). A stronger correlation between SARS-CoV-2 NT Abs and total IgG level was observed at T0 (r = 0.76;p < 0.0001) compared to T1 (r = 0.27, p = 0.0081). No correlation as regards the number of days was observed from the first to the third vaccination and SARS-CoV-2 NT Abs/total IgG. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to wild type strain (p = 0.0004) and 12-fold lower compared to Delta strain (p = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern (VOCs) seem to confirm the vaccine lower activity. (Table Presented).

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study.

BACKGROUND: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. PATIENTS AND METHODS: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. RESULTS: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). CONCLUSIONS: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity.

A one-year survey on cancer patients affected by SARSCoV-2 infection: Clinical characteristics and disease evolution in a single Institution experience

Background: Patients affected by cancer are considered particularly susceptible to SARS-CoV-2 infection complications. We aimed to study the effect of COVID on patients with solid tumors at our Oncology Unit at Policlinico San Matteo of Pavia. Material and methods: Data of patients affected by solid tumors and COVID-19 were extracted from medical records between February 21, 2020 and May 15, 2021. COVID diagnosis was confirmed by RT-PCR on nasal swab. Associations between demographic, clinical characteristics and outcomes were measured with HR with 95%CI using Cox regression. Results: Seventy-five patients affected by solid tumors with COVID diagnosis were included in the analysis. The incidence of SARS-CoV-2 infection in our cancer patients was similar to that observed in the global Italian population (5.8 vs 6.2%), but lower compared to the local population of Lombardia (8.2%) and Pavia (7.9%). In 34 patients (45.9%) COVID diagnosis was obtained through screening, in 40 patients (54.1%) because of symptoms or radiologic findings. Median age was 64.4 years (25th-75th 56-75);the majority had an ECOG PS of 0-1 (89.2%), was affected by breast, lung or gastro-intestinal cancer (28.0, 26.7 and 21.3% respectively), had stage IV disease (72.2%) and was on therapy at the time of COVID (76.0%);26 patients (36.1%) were hospitalized;21 patients (28.0%) died, 13 of them (17.3%) for COVID complications. COVID determined a median delay of the oncologic treatment of 14.0 days (25th-75th 0-25). Mortality rate was higher in our cancer population than that observed in the global Italian population (3.0%), in local population of Lombardia (4.0%) and Pavia (5.9%). In the univariable analysis, being older than 66 years (HR: 2.64, 95%CI 1.06-6.55, p=0.029), with ECOG PS ≥ 2 (HR: 5.81, 95%CI 2.18-15.49, p=0.002), >1 comorbidities (HR: 2.72, 95%CI 1.14-6.48, p=0.023), having dyspnea at the time of COVID diagnosis (HR: 6.10, 95%CI 2.37-15.68, p=0.0001), and being hospitalized (HR: 6.75, 95%CI 3.06-36.89, p<0.001) were associated with increased risk of death. In multivariable analysis, ECOG PS ≥ 2, dyspnea, hospitalization and days of treatment delay were associated with increased risk of death. Conclusions: The incidence of SARS-CoV-2 infection in our cancer patients was lower than that observed in the local population of Lombardia and Pavia, while mortality rate was higher. Predictive factors of death in cancer population correlate consistently with those alrealy published about global population.

Serum lactate dehydrogenase level may predict residual functional impairment in patients with previous CoViD-19

Background and Aim: We know that serum LDH has been identified as an important biomarker for the activity and severity of idiopathic pulmonary fibrosis. In patients with severe pulmonary interstitial disease the increase of LDH is significant and is one of the most important prognostic markers of lung injury. LDH levels have been found higher in CoViD-19 patients than in patients with SARS-CoV-2 negative confirmed pneumonia. Elevated LDH values were associated with severe CoViD-19. Aim of study is to evaluate, whether even in patients recovered from CoViD-19, LDH could be considered a marker of bad outcome and if it is associated with the development of pulmonary fibrosis or reduced performance at 6-minute walking test (6MWT). Materials and Methods: Retrospective study on 40 patients with previous CoViD-19, 3 months after viral nucleic acid tests turned negative. All patients underwent a chest CT (Lung Score - LS), lung Ultrasound (Lung US Score - LUS) and 6MWT. Results: LDH was directly related both to LS (r= 0.607;p= 0.002) and LUS (r= 0.63, p= 0.001). Moreover, the mean LDH value was significantly higher in patients with pathological 6MWT (256.8±70 vs 191.3±55.5;p= 0.030) and in patients with greater degree of dyspnea at the end of 6MWT (223.7±58.3 vs 165.6±53;p= 0.014). LDH was greater in patients with fibrous stripes on CT (228.8±67.1 vs 173.8±50.2;p= 0.026). Conclusions: LDH can be considered a potential bad outcome marker in post-CoViD as it is associated with the presence of fibrous stripes with worse performance at 6MWT and higher LS and LUS score.

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up.

BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.