Clustering Analysis Identified Distinct Clinical Phenotypes among Hemodialysis Patients in Their Immunological Response to the BNT162b2 mRNA Vaccine against SARS-CoV-2.

Background: The 2019 coronavirus disease (COVID-19) pandemic induced a major health crisis worldwide, notably among end-stage kidney disease (ESKD) patients. Vaccination against SARS-CoV-2, especially with messenger RNA (mRNA) vaccines, is highly effective and reduces hospitalization and mortality in both the general and ESKD populations. Age and previous COVID-19 infection have been identified as major determinants of the vaccine response in both the general population and ESKD patients. Methods: To determine the specific phenotype of ESKD patients in relation to their vaccine response, a clustering approach was used in a cohort of 117 fully vaccinated patients. Results: Clustering revealed three distinct clinical phenotypes among hemodialysis patients in terms of immunological response. Two clusters, consisting of either women with a long dialysis history or male subjects with diabetes with a moderate history of dialysis, exhibited low levels of IgG anti-spike antibodies. The third cluster consisted of non-diabetic middle-aged men with a moderate dialysis vintage and a very good serological response to vaccination. Conclusions: These vaccinal phenotypes of dialysis patients are easily identifiable in current practice, allowing for differential serological follow-up and tailored booster SARS-CoV-2 vaccination.

Evaluation of inflammatory biomarkers and their association with anti-SARS-CoV-2 antibody titers in healthcare workers vaccinated with BNT162B2.

Introduction: Vaccine-induced immunity against COVID-19 generates antibody and lymphocyte responses. However, variability in antibody titers has been observed after vaccination, and the determinants of a better response should be studied. The main objective of this investigation was to analyze the inflammatory biomarker response induced in healthcare workers vaccinated with BNT162b2, and its association with anti-Spike (a SARS-CoV-2 antigen) antibodies measured throughout a 1-year follow-up. Methods: Anti-spike antibodies and 92 biomarkers were analyzed in serum, along with socio-demographic and clinical variables collected by interview or exploration. Results: In our study, four biomarkers (ADA, IL-17C, CCL25 and CD8α) increased their expression after the first vaccine dose; and 8 others (uPA, IL-18R1, EN-RAGE, CASP-8, MCP-2, TNFß, CD5 and CXCL10) decreased their expression. Age, body mass index (BMI), smoking, alcohol consumption, and prevalent diseases were associated with some of these biomarkers. Furthermore, higher baseline levels of T-cell surface glycoprotein CD6 and hepatocyte growth factor (HGF) were associated with lower mean antibody titers at follow-up, while levels of monocyte chemotactic protein 2 (MCP-2) had a positive association with antibody levels. Age and BMI were positively related to baseline levels of MCP-2 (ß=0.02, 95%CI 0.00-0.04, p=0.036) and HGF (ß=0.03, 95%CI 0.00-0.06, p=0.039), respectively. Conclusion: Our findings indicate that primary BNT162b2 vaccination had a positive effect on the levels of several biomarkers related to T cell function, and a negative one on some others related to cancer or inflammatory processes. In addition, a higher level of MCP-2 and lower levels of HGF and CD6 were found to be associated with higher anti-Spike antibody titer following vaccination.

Serosurveillance among urban slum and non-slum populations immunized with COVID-19 vaccines in Bangladesh.

Using two rounds of serosurveillance, we aimed to observe the COVID-19 vaccination status and the dynamics of antibody responses to different vaccines among urban slum and non-slum populations of Bangladesh. Adults (>18 years) and children (10-17 years) were enrolled in March and October 2022. Data including COVID-19 vaccine types and dosage uptake were collected. SARS-CoV-2 spike (S)-specific antibodies were measured in blood. The proportion of vaccinated children was significantly lower among slum than non-slum populations. Two doses of vaccines showed an increase in the level of anti-S-antibodies up to 2 months, followed by reduced levels at 2-6 months and a resurgence at 6-12 months. Children showed significantly higher anti-S-antibodies after two doses of the Pfizer-BioNTech vaccine than adults; however, after 6 months, the level of antibodies declined in younger children (10 - < 12 years). In a mixed vaccine approach, mRNA vaccines contributed to the highest antibody response whether given as the first two doses or as the third dose. Our findings emphasized the need for increasing the coverage of COVID-19 vaccination among slum children and booster dosing among all children. The use of mRNA vaccines in the mixed vaccination approach was found to be useful in boosting the antibody response to SARS-CoV-2.

Effects of Antibodies in the Serum After the Administration of COVID Vaccines and Their Hematological and Cardiovascular Complications.

The outbreak of COVID-19 was seen first in Wuhan, China, on December 31, 2019. Following this, the virus has emerged, mutated, and spread to all parts of the world, taking many lives. Scientists and healthcare workers all over the world have been involved in developing vaccines and drugs to prevent the deadly virus from spreading. In this review article, we focus on how the human body responds to immune responses by producing antibodies against our immune system and serum levels in different age groups. Few studies are being considered, which include data collected from adults in the UK community, health workers from Oxfordshire, studies from the UK, healthcare workers at a university healthcare center in Turkey, and lastly, non-seropositive and seronegative healthcare workers in the USA children's hospital, respectively, and their responses to the goal. In addition to focusing on this study and its results, we also discuss the role of different vaccines and their development and antibody responses in the body due to natural and post-vaccine infections that include both doses in humans. We focus mainly on immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum produced by plasma cells, as they are involved in the first line of defense against the disease. With the development of effective vaccines and their production, trial, and market distribution to needy people, there are certain prospects for slowing down the progression of the virus, reducing mortality, and preventing re-infection in humans. However impactful and beneficial these vaccines have proven, they also carry a certain amount of danger to the people taking them. We also discuss in this article certain infrequent hematological and cardiovascular complications of the vaccine and their effect on the population.

Torquetenovirus Loads in Peripheral Blood Predict Both the Humoral and Cell-Mediated Responses to SARS-CoV-2 Elicited by the mRNA Vaccine in Liver Transplant Recipients.

Three years into the COVID-19 pandemic, mass vaccination campaigns have largely controlled the disease burden but have not prevented virus circulation. Unfortunately, many immunocompromised patients have failed to mount protective immune responses after repeated vaccinations, and liver transplant recipients are no exception. Across different solid organ transplant populations, the plasma levels of Torquetenovirus (TTV), an orphan and ubiquitous human virus under control of the immune system, have been shown to predict the antibody response after COVID-19 vaccinations. We show here a single-institution experience with TTV viremia in 134 liver transplant recipients at their first or third dose. We found that TTV viremia before the first and third vaccine doses predicts serum anti-SARS-CoV-2 Spike receptor-binding domain (RBD) IgG levels measured 2-4 weeks after the second or third dose. Pre-vaccine TTV loads were also associated with peripheral blood anti-SARS-CoV-2 cell-mediated immunity but not with serum SARS-CoV-2 neutralizing antibody titers.

Humoral Immune Response after COVID-19 mRNA Vaccination in Patients with Liver Cirrhosis: A Prospective Real-Life Single Center Study.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (ß = -0.32 [-0.64, -0.04], p = 0.027) and past-HCV-infection (ß = -0.31 [-0.59, -0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

Anti-spike Antibody Status in Pre-vaccinated Healthy Participants and Rheumatoid Arthritis Patients During the Third Wave of COVID-19.

Introduction Anti-spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced after infection with the coronavirus disease of 2019 (COVID-19) will offer protection and prevent re-infection for a few months. Seroprevalence studies measuring the SARS­CoV-2 immunoglobulin G (IgG) levels will be helpful to know the herd immunity level that prevents community transmission. Very few studies have addressed the antibody titer among healthy participants and rheumatoid arthritis (RA) patients. The present study was conducted to determine the anti-spike SARS-CoV-2 antibody (Ab) status before COVID-19 vaccination in healthy participants and RA patients. Methodology A cross-sectional study was conducted at a tertiary care hospital to estimate the serum anti-spike antibody levels against COVID-19 among the pre-vaccinated healthy participants and patients with RA during the third wave of COVID-19. After receiving written informed consent, participants were recruited as per the inclusion and exclusion criteria. Demographic details, co-morbid status, and medication details were collected. Five milliliters of blood samples were collected, and anti-spike antibodies were estimated. The SARS-CoV-2 Ab positivity rate was expressed in percentage and was correlated with gender and age groups. Ab-positive participants were classified into three categories based on the neutralizing antibody titers (NAT). Results A total of 58 participants (49 healthy volunteers and nine RA patients) were recruited. Out of 58 participants, 40 were males, nine were females among healthy participants, and one male and eight females in the RA group were enrolled. Among the RA patients, one participant was found to have the chronic obstructive pulmonary disease (COPD), and two participants with hypothyroidism. Antibody positivity was found to be 83.6% among the healthy volunteers and 100% in the RA patients. About 48% had NAT between 50 and 90%. There was no significant difference for age and gender-specific positivity for SARS-CoV-2 neutralizing antibodies and neutralizing antibody titers among healthy participants. Conclusion Our study showed 84% positivity for anti-spike SARS-CoV-2 antibodies around the third wave (between November 2021 and February 2022). The majority had high neutralizing antibody titers. The probable reason for the SARS-CoV-2 antibody positivity before vaccination was either asymptomatic infection or herd immunity.

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies.

BACKGROUND: Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine. METHODS: Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA. RESULTS: IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3. CONCLUSION: The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

Induction of neutralizing antibodies in CLL patients after SARS-CoV-2 mRNA vaccination: a monocentric experience.

Vaccination represents the best strategy to fight COVID-19 pandemics, especially in immune compromised subjects. In chronic lymphatic leukemia patients, a marked impairment of the immune response to mRNA SARS-CoV-2 vaccine was observed. In this report, we analyzed anti-RBD and neutralizing antibodies in CLL patients after two doses of mRNA SARS CoV 2 vaccine and evaluated the impact of Bruton kinase inhibitory agents. Twenty-seven CLL patients vaccinated with mRNA vaccines against SARS CoV-2 were recruited. Serum IgG, IgM and IgA anti-RBD antibodies and neutralizing antibodies were detected, and antibody avidity was measured. Peripheral blood leukocytes subsets were evaluated by flow cytometry. After two vaccine doses anti-RBD IgG were produced in 11/27 (40.5%) of patients and levels of IgG and IgA anti RBD in CLL patients were sensibly lower than in controls. Neutralizing antibodies were detectable in 12/27 (44.5%) of the patients and their level was lower than that observed in controls. Disease burden and treatment with Bruton kinases inhibitors markedly impaired vaccine induced antibody response. However, in responder patients, antibody avidity was comparable to normal subjects, indicating that the process of clonal selection and affinity maturation takes place as expected. Taken together, these data confirm the impact of disease burden and therapy on production of anti-RBD and neutralizing antibodies and support the current policy of vaccinating CLL patients.

Long-Term Dynamic Humoral Response to SARS-CoV-2 mRNA Vaccines in Patients on Peritoneal Dialysis.

Introduction. Patients on peritoneal dialysis (PD) present an impaired humoral response against SARS-CoV-2, at least after the initial vaccination and booster dose. Until now, the effect of a fourth dose has not been established. The aim of the present study is to evaluate the long-term dynamics of the humoral response of PD patients to multiple doses of SARS-CoV-2 vaccines, focusing on the effect of the fourth dose. Methods. This is an analysis of the prospective and multicentric SENCOVAC study. We included patients on PD without additional immunosuppression that had received at least 3 SARS-CoV-2 mRNA vaccine doses. We evaluated anti-spike antibody titers after the initial vaccination, third and fourth doses, using prespecified fixed assessments (i.e., baseline, 28 days, 3, 6, and 12 months after completing the initial vaccine schedule). Breakthrough infections were also collected. Results. We included 164 patients on PD (69% males, 62 ± 13 years old). In patients who had received only two doses, the rates of positive humoral response progressively decreased from 96% at 28 days to 80% at 6 months, as did with anti-spike antibody titers. At 6 months, 102 (62%) patients had received the third vaccine dose. Patients with the third dose had higher rates of positive humoral response (p = 0.01) and higher anti-spike antibody titers (p < 0.001) at 6 months than those with only 2 doses. At 12 months, the whole cohort had received 3 vaccine doses, and 44 (27%) patients had an additional fourth dose. The fourth dose was not associated to higher rates of positive humoral response (100 vs. 97%, p = 0.466) or to statistically significant differences in anti-spike antibody titers as compared to three doses (p = 0.371) at 12 months. Prior antibody titers were the only predictor for subsequent higher anti-spike antibody titer (B 0.53 [95%CI 0.27−0.78], p < 0.001). The 2 (1.2%) patients that developed COVID-19 during follow-up had mild disease. Conclusions. PD presents an acceptable humoral response with three doses of SARS-CoV-2 vaccines that improve the progressive loss of anti-spike antibody titers following two vaccine doses.

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections.

Background: Despite the high level of protection against severe COVID-19 provided by the currently available vaccines some breakthrough infections occur. Until now, there is no information whether a potential risk of a breakthrough infection can be inferred from the level of antibodies after booster vaccination. Methods: Levels of binding antibodies and neutralization capacity after the first, one and six month after the second, and one month after the third (booster) vaccination against COVID-19 were measured in serum samples from 1391 healthcare workers at the University Hospital Essen. Demographics, vaccination scheme, pre-infection antibody titers and neutralization capacity were compared between individuals with and without breakthrough infections. Results: The risk of developing an Omicron breakthrough infection was independent of vaccination scheme, sex, body mass index, smoking status or pre-existing conditions. In participants with low pre-infection anti-spike antibodies (≤ 2641.0 BAU/ml) and weaker neutralization capacity (≤ 65.9%) against Omicron one month after the booster vaccination the risk for developing an Omicron infection was 10-fold increased (P = 0.001; 95% confidence interval, 2.36 - 47.55). Conclusion: Routine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying "non"-, "low" and "high"-responders may be used as an indication for re-vaccination.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

Durability of anti-spike antibodies after vaccination with mRNA SARS-CoV-2 vaccine is longer in subjects with previous infection: could the booster dose be delayed?

PURPOSE: The long-term effectiveness of BNT162b2/Pfizer vaccine remains undetermined. This observational prospective study was designed to verify durability of antibodies against the viral receptor-binding domain (RBD) spike (S)-protein (RBD S-Protein IgG) after the second-dose administration of the vaccine among Health Care Workers (HCWs). METHODS: In all HCWs at the Poliambulanza Foundation Hospital Brescia (Italy) were quantified the levels of RBD S-Protein IgG (Abbott Diagnostics) at 45 and 240 days after the second-dose vaccine. Previous infection was defined as antibodies against SARS-CoV-2 nucleocapsid positivity (Abbott Diagnostics) before vaccination. The Mann-Whitney U test was used to compare mean levels of RBD S-Protein IgG among previously infected and uninfected HCWs. RESULTS: The mean level of the RBD S-protein IgG detected 45 days after the second dose of the vaccine was 30,041 AU/mL (95% CI 145-80,000) for the 250 previously infected HCWs and it was significantly higher (p < 0.001) than that observed in the 1121 previously uninfected subject with the mean level of 10,604 AU/mL (95% CI 165-62,241). Similarly, at 240 days in previously infected subjects the antibody titer was of 8145 AU/mL (95% CI 347-80,000) and significantly higher (p < 0.001) than that observed in the 1121 previously uninfected HCWs with a mean antibody level of 1271 AU/mL (95% CI 50-80,000). When comparing the change in mean antibody levels overtime, the previously infected HCWs presented a 72.9% reduction in RBD S-protein IgG while in the previously uninfected HCWs the reduction was 88.0%. In addition, in the HCWs group without previous infection we reported 53 new SARS-CoV-2 infections and they had a mean level of RBD S-protein IgG antibodies of 1039 AU/mL (95% CI 157-4237) at 240 days. No new infections were found in previously SARS-CoV-2 infected subjects. CONCLUSIONS: We report that the mean level of post vaccinal RBD S-protein IgG was significantly higher in the previously infected HCWs than in previously uninfected subjects at 45 and 240 days after the second-dose vaccine. Moreover, our data suggest that the risk of a new SARS-CoV-2 infection was higher in the previously uninfected HCWs than in those who had already contracted natural viral infection. The limitations of this study prevent us to draw definitive conclusions on the antibody titers and on the role of a previous SARS-CoV-2 infection in influencing the levels of post-vaccine RBD S-protein IgG. The booster dose of the vaccine could be delayed after the second dose in previously naturally infected subject and it could have an important strategic impact on the organization of the future COVID-19 vaccination campaign.

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article.

Taking into account higher risk of severe coronavirus disease 2019 or death among patients with cancer, as well as impaired immunogenicity after anti-SARS-CoV-2 vaccines, in addition to waning immunity, booster dosing appears mandatory in this patient population. This review sought to provide reasonable evidence so as to assist oncologists in their daily practice, helping them decide when an anti-SARS-Cov2 antibody (Ab) dosage should be scheduled after a full two-dose vaccination and, if necessary, propose an early third dose (D3). Such D3 could apply to non-responder patients with anti-Spike (S) Abs titres <40 binding Ab unit (BAU)/mL. For lowresponder patients with anti-S Ab titres between 40 BAU/mL and 100/260 BAU/mL (suggested area of uncertainty), an early D3 may similarly be proposed. Nevertheless, this D3 could be administered in a less urgent manner, taking into account associated comorbidities and regional epidemic incidence rates. This latter strategy may comprise a monthly dosage of anti-S titres so as to better assess the kinetics of waning immunity. For responder patients with anti-S titres above 260 BAU/mL, we suggest to follow the recommendations outlined for the general population. Given this context, patients with anti-S titres above 1000 BAU/mL should be given the possibility to undergo anti-S titre control after three months, designed to assess rapid humoral waning immunity. We strongly recommend that patients with cancer be included into observational serological monitoring studies or clinical trials that are dedicated to severe immunocompromised patients without any humoral seroconversion after D3.

First Case of COVID-19 Treated with Monoclonal Anti-Spike Antibodies in a Patient with Cystic Fibrosis in Romania.

Patients with chronic lung conditions, including cystic fibrosis, may be prone to severe COVID-19. Therefore, therapeutic intervention should be prompt and tailored to all associated comorbidities. We report the case of a 17-year-old male adolescent with cystic fibrosis and multiple chronic conditions (bronchiectasis, exocrine pancreatic insufficiency, chronic multidrug resistant Pseudomonas aeruginosa colonization, nasal polyposis, chronic sinusitis, ventricular extrasystoles and multiple drug allergies), who presented with an acute episode of productive cough, and was confirmed with moderate COVID-19 based on positive RT-PCR for SARS-CoV-2 and lung imaging showing isolated foci of interstitial pneumonia. Intravenous treatment with the monoclonal antibody cocktail casirivimab and imdevimab was administered. The evolution was favorable, with rapid remission of the inflammatory syndrome and gradual decrease of cough, without progression to severe or critical COVID-19, but with complications such as repeated hemoptysis, which was due to the patient's underlying conditions, and which required close monitoring for timely adjustment of the patient's chronic treatment.

Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2.

SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina. Seroconversion rates in unexposed subjects after the first and second doses were 40 % and 100 %, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p < 0.0001). The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p = 0.005). A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p = 0.008). Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p < 0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p < 0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects. Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels. Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

Immune Response and Effects of COVID-19 Vaccination in Patients with Lung Cancer-COVID Lung Vaccine Study.

Lung cancer patients represent a subgroup of special vulnerability in whom the SARS-CoV-2 infection could attain higher rates of morbidity and mortality. Therefore, those patients were recommended to receive SARS-CoV-2 vaccines once they were approved. However, little was known at that time regarding the degree of immunity developed after vaccination or vaccine-related adverse events, and more uncertainty involved the real need for a third dose. We sought to evaluate the immune response developed after vaccination, as well as the safety and efficacy of SARS-CoV-2 vaccines in a cohort of patients with lung cancer. Patients were identified through the Oncology/Hematology Outpatient Vaccination Program. Anti-Spike IgG was measured before any vaccine and at 3-6-, 6-9- and 12-15-month time points after the 2nd dose. Detailed clinical data were also collected. In total, 126 patients with lung cancer participated and received at least one dose of the SARS-CoV-2 vaccine. At 3-6 months after 2nd dose, 99.1% of baseline seronegative patients seroconverted and anti-Spike IgG titers went from a median value of 9.45 to 720 UI/mL. At the 6-9-month time point, titers raised to a median value of 924 UI/mL, and at 12-15 months, after the boost dose, they reached a median value of 3064 UI/mL. Adverse events to the vaccine were mild, and no SARS- CoV-2 infection-related deaths were recorded. In this lung cancer cohort, COVID-19 vaccines were safe and effective irrespective of the systemic anticancer therapy. Most of the patients developed anti-Spike IgG after the second dose, and these titers were maintained over time with low infection and reinfection rates with a mild clinical course.

Analytical and Clinical Evaluation of the Semiquantitative Elecsys Anti-SARS-CoV-2 Spike Protein Receptor Binding Domain Antibody Assay on the Roche cobas e602 Analyzer.

OBJECTIVES: To analytically and clinically evaluate the semiquantitative Elecsys anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody (S-Ab) assay on the Roche cobas e602 analyzer. METHODS: The S-Ab assay is a 1-step, double-antigen sandwich electrochemiluminescent immunoassay that semiquantitatively measures total IgG, IgM, and IgA antibodies specific for the receptor binding domain of SARS-CoV-2 spike protein in serum or plasma. The S-Ab assay was evaluated for precision, linearity, interference (by hemoglobin, bilirubin, triglycerides, and biotin), cross-reactivity, and clinical performance, and was compared to the qualitative Elecsys anti-nucleocapsid (N-Ab) immunoassay, a lateral flow device that qualitatively detects S-Ab and N-Ab, and an anti-spike enzyme-linked immunosorbent assay (ELISA). RESULTS: S-Ab assay is precise, exhibits linearity from 0.4 to 250 U/mL, is unaffected by significant cross-reactivity or interferences, and qualitatively demonstrates greater than 90% concordance with N-Ab assay and lateral flow device. Readouts of S-Ab assay correlate with ELISA, which in turn correlates strongly with SARS-CoV-2 virus neutralization assay, and exhibit 100% sensitivity and specificity for COVID-19 patient samples obtained at or more than 14 days after PCR positivity. CONCLUSIONS: The S-Ab assay is a robust clinical test for qualitative and semiquantitative detection of seropositivity following SARS-CoV-2 infection or spike-encoding mRNA COVID-19 vaccination.