ABSTRACT
Background: In most individuals, protective humoral and cellular immunity develops after two doses of the BNT162b2 Pfizer vaccine. In patients with lymphoma, humoral response is weaker and almost universally abrogated in patients who received anti-CD20 monoclonal antibodies. Whether cellular immune response is also abrogated is unknown. Aims: To determine whether patients with lymphoma develop specific T-cell mediated cellular response to BNT162b2 Pfizer vaccine. Methods: We included patients with lymphoma above the age of 18 years who received two doses of the BNT162b2 Pfizer vaccine and collected clinical and demographics data. T-cell immune response to the vaccine was analysed in patients' blood samples stimulated by spike antigen and quantified by two methods: (1) Interferon-gamma (IFNg)- release assay (IGRA, EuroImmun, Germany)- IFNg was quantified by ELISA (DuoSet, R and D Systems, Minneapolis, Minnesota, USA) and response above 50 pg/ml was considered positive. (2) Flow cytometry- Quantification of the T cell activation markers, CD134+ CD25+CD4+ T-cells was performed (Act-T4 CellTM kit, Cytognos, Spain), and any response above 0 was considered positive. Humoral response was measured by SARS-CoV-2 IgG II Quant (Abbott©) assay. The positive cut-off was set at 50AU/ml. Blood samples were drawn approximately 4 months after the second vaccination. Results: Sixty-nine lymphoma patients, treated with two vaccine doses, were included in this study. Median age was 66 (range: 30-84) and 39 (57%) were males. Sixty-two patients (90%) had non-Hodgkin lymphoma (NHL) including 18 with DLBCL, 26 with follicular lymphoma and 14 with marginal zone lymphoma. Seven (10%) patients had Hodgkin lymphoma. In this cohort, 70% (n=49) of the patients received anti CD20 MoAb, and 35% of them (n=27) were still on anti CD20 treatment. Thirteen patients received bendamustine-based immunochemotherapy. At the time of assessment (median 4.8 months after the 2nd vaccine) anti-spike antibodies were detected in only 42% (N = 29) of patients. In comparison, there was an increase in specific T cell response by any assay (IGRA and Flow) in 49% of patients (n = 34). The correlation between the IGRA and flow data was 0.7 (pearson correlation, P = 0.01). However, no correlation between humoral (qualitative and quantitative) and T cell response was shown, regardless of the assay applied. Cellular response was not corelated with the time elapsing from last immunochemotherapy. In the anti-CD20 MoAb treated cohort, of which 27 patients were still on active treatment at the time of vaccination, only 2 patients (7%) developed a humoral immune response, while cellular immunity was elicited in 52% (N = 15) patients (ELISA assay). In the Bendamustine treated cohort, with a median time from end of treatment to vaccination of 23 months (1-106 months), humoral but not cellular response correlated positively with the time from treatment completion to vaccination (p=0.04). Summary/Conclusion: The rate of cellular and humoral response to two doses of the BNT162b2 Pfizer vaccine in lymphoma patients was found to be significantly abrogated. In this small cohort, 49% of patients developed a cellular response despite a severely abrogated humoral immunity. These findings suggest that vaccine administration should be considered even early after anti CD20 therapy despite the reduced humoral immunity. These findings should be validated in studies with a higher number of patients.
ABSTRACT
Introduction: In patients with hematological malignancies, COVID-19 is considered to be associated with a high risk of severe morbidity and mortality. While anti-COVID-19 vaccination of such patients has become the standard of care, many of them fail to generate protective serological response due to either the nature of their underlying disease or exposure to therapy. Surprisingly, none of the Hodgkin lymphoma (HL) patients treated or followed at our tertiary care center, has been hospitalized for severe COVID-19. Nevertheless, the vulnerability of this patient population to infections highlights the need for efficacious protection against this life-threatening disease. The current non-interventional single-center study has aimed to evaluate the serological response in HL patients vaccinated against the virus in comparison to those HL patients who had a history of COVID-19 infection. The impact of an additional background disease or use of lymphodepleting agents on the evaluated serological response of HL patients has also been assessed. Methods: The BNT162b2 vaccine (Pfizer) was available in Israel from January 2021 and all costs were covered by the National Health Service. Thus, all patients with hematological malignancies were recommended to undergo vaccination with 2 doses of this vaccine, injected 21 days apart. The serology test was performed at least two weeks after the second vaccination. The SARS-CoV-2 IgG II Quant (Abbott©) assay was used to measure the levels of IgG antibodies against the SARS-CoV-2 spike protein. The result was considered positive if the IgG level was ≥50 AU/ml, which was defined as an adequate serological response. Results: Fifty-two HL patients were offered to have their serological response evaluated. Six declined. Sixteen patients had early-stage HL, stage I-II, and 30 had advanced disease, including 4 patients with stage IIB bulky, 9 - with stage III and 17 - with stage IV disease. Study participants received 1-9 lines of therapy (median 1 line). Twelve patients were being treated for active disease when their serology was tested. The study was approved by the Institutional Review Board (Approval #0883-20-RMB) and patients signed informed consent. Ten patients were diagnosed with COVID-19, with none of them being hospitalized. Forty-two other patients received two vaccine doses. One patient who had been diagnosed with COVID-19 and was later vaccinated with a single dose was analyzed with vaccinated patients. Serology tests were performed at a median of 132 days from COVID-19 diagnosis or 108 days from vaccination, with no statistical difference in test timing between the groups. Similarly, the median age did not differ between the groups [41 (28-64) and 43 (18-80) years, respectively;p=0.98]. Data on antibody levels were available for 7/10 patients who recovered from COVID-19, with a median antibody level equating to 113 (0-1576) AU/ml (Table 1). In the group of 39 vaccinated patients, the median antibody level was 2054 AU/ml (0-21174;p=0.007). An additional analysis was performed to compare the evaluated parameters in a subgroup of patients (n=7) who had another background disease along with HL, such as chronic lymphocytic leukemia, s/p kidney transplantation, solid tumor, or those who were heavily pretreated, including therapy with bendamustine, versus the values observed in the rest of the patients (n=39). The median age in the above subgroup was found to be 60 (38-80) years, which was significantly older than in the remaining patients [median age 41 (18-78) years;p=0.029)]. Likewise, median IgG antibody levels demonstrated significant difference between these two subgroups, equating to 2 (0-7539) AU/ml and 1993 (0-21174) AU/ml, respectively (p=0.007). Of the 36 vaccinated HL patients with no background disease 92% had adequate anti-spike antibody levels at a median of 100 days post-vaccination. Conclusions: The results of the current study suggest that at least 87% of Hodgkin lymphoma patients develop a high titer of anti-spike antibodies after vaccination with two doses of BNT162b2. Among HL patients, the antibody titer levels in vaccinated individuals are found to be 18-fold higher than in those who have recovered from COVID-19. Only a minority of HL patients who had additional background diseases or were heavily pretreated, failed to develop an adequate serological response. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Background: COVID-19 exerts deleterious cardiopulmonary effects, leading to worse prognosis in the most effected. Purpose: The aim of this retrospective multi-center observational cohort study was to analyze the trajectories of key advanced hemodynamic parameters amongst hospitalized COVID-19 patients according to different risk populations using a chest-patch wearable providing continuous remote patient monitoring. Methods: The study was conducted in five COVID-19 isolation units. Patients admitted to the units were connected to a photoplethysmography based noninvasive remote advanced hemodynamic monitor after completing a basic risk factor survey. Physiological parameters were measured every 15 minutes during the hospitalization, including cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), heart rate, blood pressure (BP), respiratory rate, blood oxygen saturation (SpO2), and body temperature. Results: 492 COVID-19 patients (179 females, average age 58.7 years) were included in the final analysis, with more than 3 million measurements collected during an average of 75.3 hours. Overall, within the first five days of hospitalizations we found a significant increase in SVR, and a significant decrease in SpO2, DBP, CO and CI (p<0.01 for all). The changes were more prominent in high risk populations- males, older age and obesity and had a temporal correspondence to changes in respiratory parameters. Conclusions: This is the first comprehensive continuous advanced hemodynamic profiling of COVID-19 patients. Worse hemodynamic status was prominent in high risk populations.