ABSTRACT
Background: Adapted anti-SARS- CoV- 2 vaccination schedules have been recommended for patients with IMID due to a higher risk of reduced vaccine response. Nonetheless, there is little data on how different vaccine schedules influence immune responses and on the long-term persistence of vaccination responses in this subset. Purpose(s): The aim of this study is to assess the long-term course of humoral responses to SARS-CoV- 2 vaccines in a large prospective cohort of IMID patients and non-IMID controls with up to 10 months of follow-up following the first vaccine dose. Method(s): In February 2020, we started a prospective cohort of IMID patients and healthy controls (HC) to evaluate immune responses to SARS-CoV- 2 vaccines and infection (1). Individuals who provided data starting 4 weeks before their first vaccination and forward were included. Serum anti-SARS- CoV- 2 spike protein IgG were measured by ELISA (EUROIMMUN, Lubeck, Germany) in units of Optical density (OD) at 450 nm. An OD <1.1 was considered as poor response. We used time splines to fit linear mixed-effect models for log-transformed antibody levels and logistic mixed-effects models, adjusting for age and sex to estimate marginal mean antibody levels and adjusted risk of poor response with 95 percent confidence intervals. Antibody levels of twice-vaccinated patients were also compared to those who received 3 vaccinations. Result(s): Between December 2020 and December 2021, 3733 IMID patients and HC contributed 5564 samples, with a median (IQR) follow-up of 23.3 (13.9-0.9) weeks following first immunization (Table 1). By the date of their most recent sampling, 3280 (88%) participants had received two vaccines and 241 (6%) received three. Age and sex-adjusted estimated marginal mean IgG in IMID patients declined after week 10 and were significantly lower at all timepoints compared to controls (Figure 1A, Table 1). Adjusted risk of poor response at week 40 was 2.9% (1.4%-6.1%) in HC whereas 26.1% (15.8-40.0) in IMID (Figure 1B). After a median 20 (10-26). weeks from the second dose, 147 (6%) IMID patients had received a third dose. Adjusted mean antibody levels at 40 weeks in IMID patients who received three vaccine doses were higher than in HC who received two doses (Figure 1C). Conclusion(s): IMID patients had a weaker humoral response to SARS-CoV- 2 vaccination than controls at all time points following the first dose with a high risk of poor response at 40 weeks. Nonetheless, a third dose in IMID patients could provide higher antibody levels compared to unboosted healthy individuals.
ABSTRACT
Introduction: Infection with the new coronavirus SARS-CoV-2 leads to the disease COVID-19, the course of which is highly variable and depends on a number of patient-specific risk factors. Tumor patients (pts) are considered to be at risk for a severe course of COVID-19, however represent a heterogenous group with presumably variable risk. The infuence of tumor type, specific cancer treatment modalities and other tumor-specific factors on the outcome of COVID-19 are unknown. Method(s): Pts with proven SARS-CoV-2 infection and established tumor diagnosis are eligible for the multicentric ADHOK coronavirus tumor registry (CoRe). Detailed information about tumor diagnosis and treatment were retrospectively collected. The outcome of the SARS-CoV-2 infection (COVID-19 severity) was graded according to the WHO. Result(s): As of 10 July 2020, 77 pts (54.6% male, 45.4% female) out of 15 german medical institutions were included in the registry. Median age was 71 (range 37-94) years. 49 pts (63.6%) were diagnosed with solid tumors, 28 pts (36.4%) sufered from hematological diseases. Most of the pts registered (59.7%) had active tumor disease, 23% pts were in partial or complete remission. 39 pts (40.3%) were at the time-point of SARS-CoV-2 infection under active tumor treatment, the majority of them (22 pts) were receiving systemic anti-tumor agents. In 55 of the pts (71.4%), the SARS-CoV-2 infection remained either asymptomatic (19 patients), or the course of COVID-19 was mild (20 pts) or moderate (16 pts). In contrast, 22 pts (28.6%) experienced a servere or critical course of the disease, and 14 pts (18.2%) died from the infection. Lethal outcome of COVID-19 was documented in 11 of 49 pts with solid tumors (22.4%) and in 3 of 28 pts (10.7%) with hematological diseases. The mortality of SARS-CoV-2 infection was higher in pts with active tumor disease (10/46 pts, 21.7%) than in those with remission (2/18 pts, 11.1%), but was similar in pts with active tumor treatment (15.5%) versus no active tumor treatment (19.3%). Conclusion(s): The outcome of SARS-CoV-2 infection in pts with tumor diseases is highly variable. In the current registry, a considerable number of asymptomatic and mild infections is documented, suggesting that there may be a group of tumor pts with low risk for complications of COV-ID-19. In contrast, detailed analysis of pts with a severe and lethal course of the disease is required to identify potential factors posing those pts at risk for the infection.
ABSTRACT
Background: The frst vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated infammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identifed leading to specifc vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specifc recommendations are lacking. Objectives: To evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the frst vaccine dose. Methods: We have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their frst vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantifed with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We ftted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confdence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations. Results: Among 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the frst vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, fnally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B). Conclusion: Humoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the frst vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.
ABSTRACT
Background: Patients with immune-mediated infammatory diseases (IMID), particularly if treated with B-cell depleting therapies, show reduced humoral responses to SARS-CoV-2 vaccines and increased risk of severe COVID-19 (1,2). Since pre-exposure prophylaxis (PrEP) with monoclonal antibodies against SARS-CoV-2 proved effective in preventing infection and COVID-19 (3) in the general population, PrEP could be used for passive immunization of vaccine-refractory patients with IMIDs. Objectives: To evaluate the persistence of serum and salivary anti-SARS-CoV-2 IgG antibodies in vaccine-refractory patients with IMID after PrEP with casiriv-imab/imdevimab. Secondary outcomes were safety, SARS-CoV-2 infection, and adverse COVID-19 outcomes. Methods: We performed a longitudinal analysis on anti-SARS-CoV-2 IgG titers in IMID patients who received a PrEP with 1200 mg of subcutaneous casirivimab/imdevimab due to high infection risk, as they had not developed an adequate humoral response at least 21 days after three COVID-19 vaccinations (Table 1). Serum and salivary anti-SARS-CoV-2 Spike IgG were quantifed by ELISA (EUROIMMUN, Lübeck, Germany) before PrEP and after 1, 14, and 30 days. IgG levels are given as antibody ratios by dividing the optical density of the sample by that of the calibrator. A cutoff of ≥1.1 was considered positive. Safety as well as polymerase chain reaction (PCR)-confrmed SARS-CoV-2 infection and adverse COVID-19 outcomes (hospitalization, mechanical ventilation, death) after PrEP were recorded. Results: We obtained 92 serum and 75 saliva samples from 26 participants at four consecutive timepoints (Figure 1). Anti-SARS-CoV-2 IgG titers were observed in serum and saliva samples of all participants from day 1 and throughout 30 days after PrEP independently of diagnosis, therapy, total IgG, and peripheral CD19+ B-cells. Serum IgG increased rapidly at day 1 and plateaued from day 14 to 30 (Figure 1A), reaching similar levels as seen in healthy subjects after full vaccination (1), while saliva IgG increased steadily from administration up to day 14 and plateaued at day 30 (Figure 1B). No side effects were reported. Five patients (19.2%) had a close contact with a SARS-CoV-2-infected person, after which all but one remained asymptomatic and with a negative PCR test. The patient who tested positive developed mild COVID-19 with fever and cough. Conclusion: SARS-CoV-2 PrEP induces stable serum and salivary antibody levels in IMID patients who did not respond to COVID-19 vaccination, regardless of pre-existing clinical and serological features. In IMID, PrEP with casiriv-imab/imdevimab is safe and has the potential to prevent infection and severe COVID-19.
ABSTRACT
Introduction: Cancer patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection, however, represent a heterogeneous population with variable risk. Pts. with active tumor disease and hematological neoplasms are particularly vulnerable to the infection. In a retrospective analysis of the ADHOK coronavirus tumor registry, the absolute neutrophil count (ANC) determined prior to infection showed a strong and independent correlation with COVID-19 mortality (Kiani et al, Cancer Med, in press). Here, we present an extended analysis of pre-infection laboratory parameters and COVID-19 severity in the registry pts., with the aim to establish an objective and easy-to-obtain predictor of infection outcome. Methods: Pts. with malignant tumor disease and PCR-confirmed SARSCoV- 2 infection were included in the registry by 22 German clinical institutions. Detailed information about tumor disease and treatment was collected retrospectively. Results of routine laboratory testing, performed at least 10 days prior to infection, were obtained. The course of SARSCoV- 2 infection was graded according to the WHO. Results: By May 10, 2021, 268 pts. (68% with solid tumors, 32% with hematological neoplasms) were included in the registry. Pre-infection routine laboratory values were available from 166 pts., obtained at a median of 21 days before infection. The pre-infection ANC, the neutrophil-to-lymphocyte ratio, and serum levels of CRP and LDH significantly correlated with COVID-19 severity after infection. In multivariable analysis, the ANC was found to be the strongest prognostic predictor for COVID-19 mortality (ANC > 4,4 /nL: OR 10.5, p=0.02) and was independent of age, sex, tumor activity, and CRP. Combining ANC and CRP to a score of 0, 1, or 2 points allowed to separate three groups of pts. with significantly different COVID-19 mortality (2% vs. 29 % vs. 64%, p< 0.001). Significant association of the 'pre-infection COVID-19 score' with COVID-19-related mortality was consistently found in the first and second waves of the pandemic and, in multivariable analysis, was independent of pre-infection LDH, a surrogate marker for tumor activity. Conclusions: A combined score of pre-infection ANC and CRP, determined as part of routine clinical testing prior to SARS-CoV-2 infection, strongly and consistently correlates with COVID-19 severity in cancer pts. It may serve as an easy-to-obtain parameter for COVID-19 risk assessment of cancer pts. prior to infection.
ABSTRACT
Background: Tumor patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection. However, they represent a heterogeneous group of individuals with variable risk. Identification of vulnerable subgroups is important for prioritization of vaccination strategies and possible early therapeutic intervention after infection. Methods: Tumor pts. with PCRconfirmed SARS-CoV-2 infection were included in the multicentric ADHOK registry by 22 institutions. Detailed information about tumor disease and treatment, as well as routine laboratory parameters determined at least 10 days prior to SARS-CoV-2 infection, was collected retrospectively. The primary endpoint was defined as the outcome of the SARS-CoV-2 infection, graded according to the WHO: asymptomatic, mild, moderate, severe, critical, and COVID-19-related death. Results: Until Feb. 5, 2021, 215 pts. (67% with solid tumors, 33% with hematological neoplasms) were included in the registry. 74% of the pts. had an active malignancy. The course of SARS-CoV-2 infection was rather variable: 66% of the pts. remained asymptomatic or showed a mildto- moderate course, while the rest developed severe or critical disease. The COVID-19-related mortality rate was 24%. Pre-infection routine laboratory values were available for 104 pts., obtained at a median of 21 days before SARSCoV- 2 infection. Compared to COVID-19 survivors, COVID-19 non-survivors showed significantly higher median levels of absolute neutrophil count (ANC: 3.6 vs. 6.4 /nL;p = 0.006, n = 91), neutrophil-to-lymphocyte ratio (NLR: 2.2 vs. 7.2;p = 0.005, n = 75), C-reactive protein (CRP: 9.9 vs. 42.0 mg/L;p = 0.001, n = 104), and lactate dehydrogenase (LDH: 213.0 vs. 267.0 U/L;p = 0.016, n = 78). When categorized by a median split, COVID-19 mortality was significantly higher in pts. with ANC > 4.4 /nL (4% vs. 55%, p < 0.001), NLR > 4.1 (5% vs. 58%, p < 0.001), CRP > 15.4 mg/L (18% vs. 46%, p = 0.003), LDH > 236 U/L (15% vs. 49%, p = 0.003) and lymphocytes < 1.3 /nL (41% vs. 11% p = 0.002). In multivariable analysis, ANC and CRP showed a strong and significant association with COVID-19-related death (OR 23.0 and 7.7, p = 0.007 and 0.029, respectively). To develop an easy-to-apply preinfection score, we combined ANC and CRP and were able to separate three groups of pts. With significantly different COVID-19 outcomes (p < 0.001) (Table). Conclusions: Our results unveil subgroups of tumor pts. who may be at increased risk of severe COVID-19 and point to preinfection routine laboratory parameters with potential prognostic power: ANC and CRP may help identify pts. at risk for severe COVID-19 before SARS-CoV-2 infection.