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1.
Current Pharmacology Reports ; 8(2):149-170, 2022.
Article in English | EMBASE | ID: covidwho-1813961

ABSTRACT

The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2. Proteins and ligand were generated using AutoDock 1.5.6 software. Binding affinity of methylxanthines with SARS-CoV-2 target proteins was determined using Autodock Vina. MD simulation of the best interacting complexes was performed using GROMACS 2018.3 (in duplicate) and Desmond program version 2.0 (academic version) (in triplicate) to study the stabile interaction of protein–ligand complexes. Among the selected methylxanthines, theophylline showed the best binding affinity with all the three targets of SARS-CoV-2 (6LZG − 5.7 kcal mol−1, 6LU7 − 6.5 kcal mol−1, 6M3M − 5.8 kcal mol−1). MD simulation results of 100 ns (in triplicate) showed that theophylline is stable in the binding pockets of all the selected SARS-CoV-2 proteins. Moreover, methylxanthines are safer and less toxic as shown by high LD50 value with Protox II software as compared to drug chloroquine. This research supports the use of methylxanthines as a SARS-CoV-2 inhibitor. It also lays the groundwork for future studies and could aid in the development of a treatment for SARS-CoV-2 and related viral infections. Graphical : [Figure not available: see fulltext.].

2.
Journal of Clinical and Diagnostic Research ; 16(4):LC37-LC42, 2022.
Article in English | EMBASE | ID: covidwho-1791828

ABSTRACT

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has imposed an unprecedented burden on our healthcare system. Serological testing for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies serves as an useful marker for determining an infection by the virus in the recent past and the immune response. The immune response, including the humoral response to the infection is one of them and the knowledge in this area is still evolving. Virus specific antibodies are expected to help in eliminating the virus and to provide protective immunity against reinfection. Aim: To serially monitor the total antibody response to SARSCoV-2 in order to gain better insight into the duration of antibody persistence. Materials and Methods: This prospective observational study was conducted in 66 Healthcare Workers (HCW) with a history of Reverse Transcription- Polymerase Chain Reaction (RT-PCR) proven COVID-19 infection. The study was conducted between May 2020 to April 2021 at the Suburban diagnostics Central Processing Laboratory, Mumbai, Maharashtra, India. Serum samples were serially examined for the presence of total antibodies against the Nucleocapsid (N) protein of SARS-CoV-2 upto 180 days postinfection. A further follow-up examination was done at 360 days. A qualitative Electrochemiluminescence Immunoassay (ECLIA) assay was used for assessment of the antibody response. The chi-square or Fisher-exact test was used to compare categorical variables and the Mann-Whitney U test, Kruskal Wallis test and student t-test were used to compare continuous variables across groups. For assessing relationship between variables, the Pearson test or linear regression were used as appropriate. Results: Out of 66 healthcare workers, 32 were male (48.5%) and 34 were females (51.5%) with the median age of 29.5 years. Out of 66 cases, 62 (94%) cases developed antibodies against SARS-CoV-2 at different time intervals, 48 cases during the 14-30 day interval, 10 cases during the 31-60 day interval, three cases during the 61-90 day interval and one case during the 90-120 days interval. Thirty one out of 35 (88%) cases that could be followed-up at 360 days showed persistence of antibodies. No patient reported symptoms which would warrant a repeat RT-PCR test. Conclusion: This study showed that the antibody response to SARS-CoV-2 virus was sustained for 12 months postinfection in most cases. The absence of fresh infection in these cases during the study period suggests that the antibodies might protect against reinfection with the virus. So, it may be safe to defer vaccination in postinfection cases by 6-9 months thereby saving precious resources.

3.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-333245

ABSTRACT

SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that first emerged in late 2019 and has since triggered a pandemic of acute respiratory disease named COVID-19 which poses a significant threat to all public health institutions in the absence of specific antiviral treatment. Since the outbreak began in March 2020, India has reported 4.77 lakh Coronavirus deaths, according to the World Health Organization (WHO). The innate RNA interference (RNAi) pathway, on the other hand, allows for the development of nucleic acid-based antiviral drugs in which complementary small interfering RNAs (siRNAs) mediate the post-transcriptional gene silencing (PTGS) of target mRNA. Therefore, in this current study, the potential of RNAi was harnessed to construct siRNA molecules that target the consensus regions of specific structural proteins associated genes of SARS-CoV-2, such as the envelope protein gene (E), membrane protein gene (M), nucleocapsid phosphoprotein gene (N), and surface glycoprotein gene (S) which are important for the viral pathogenesis. Conserved sequences of 811 SARS-CoV-2 strains from around India were collected to design 21 nucleotides long siRNA duplex based on various computational algorithms and parameters targeting E, M, N and S genes. The proposed siRNA molecules possessed sufficient nucleotide-based and other features for effective gene silencing and BLAST results revealed that siRNAs' targets have no significant matches across the whole human genome and hence, siRNAs were found to have no off-target effects on the genome, ruling out the possibility of off-target silencing. Finally, out of 157 computationally identified siRNAs, only 4 effective siRNA molecules were selected for each target gene which is proposed to exert the best action based on GC content, free energy of folding, free energy of binding, melting temperature, heat capacity and molecular docking analysis with Human AGO2 protein. Our engineered siRNA candidates could be used as a genome-level therapeutic treatment against various sequenced SARS-CoV-2 strains in India. However, future applications will necessitate additional validations in vitro and in vivo animal models.

4.
Blood ; 138(SUPPL 1):1628, 2021.
Article in English | EMBASE | ID: covidwho-1770286

ABSTRACT

Background Plasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period. Methods A clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records. Results 188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112);of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive;of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48- 2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection. Conclusion Serological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited. (Figure Presented).

5.
American Journal of Obstetrics and Gynecology ; 226(1):S156-S157, 2022.
Article in English | EMBASE | ID: covidwho-1757067

ABSTRACT

Objective: To explore maternal humoral immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the rate of vertical transmission. Study Design: A prospective cohort study was conducted at two university-affiliated medical centers. Women positive for SARS-CoV-2, as determined by reverse-transcription-polymerase-chain-reaction (RT-PCR), during pregnancy were enrolled just prior to delivery. Levels of anti-SARS-CoV-2 nucleocapsid IgG, spike IgG and spike-IgM were tested in maternal and cord blood at delivery, and neonatal nasopharyngeal swabs were subjected to PCR testing. The primary endpoint was the rate of vertical transmission, defined as either positive neonatal IgM, positive neonatal IgG with sero-negative mother or positive neonatal PCR. The rate of vertical transmission was estimated to be 7% when defined by RT-PCR. Assuming that using serology tests increases the rate to 10% versus 0% in non-infected population, 71 women were required (80% power, 5% one-sided alpha) Results: Among 72 women, 36 (50%), 39 (54%) and 30 (42%) were positive for anti-spike-IgM, anti-spike-IgG and anti-nucleocapsid-IgG, respectively (p < 0.0001 for IgG antibodies;table). At least 8/72 (11%) neonates were infected in utero;one had a positive PCR and seven had positive IgG while their mothers were seronegative for the same IgG. IgM was not detected in cord blood. Anti-nucleocapsid-IgG and anti-spike-IgG were detected in 83% and 85% of neonates of seropositive mothers, respectively (Pearson coefficient correlation 0.8, p< 0.001). The highest rate of positive maternal serology tests was 8-12 weeks post-infection (89% anti-spike IgG, 78% anti-spike IgM and 67% anti-nucleocapsid IgG). Thereafter, the rate of positive serology tests declined gradually;at 20 weeks post-infection, only anti-spike IgG was detected in 33-50% (figure). Conclusion: The rate of vertical transmission was at least 11%. Vaccination should be considered 3 months post-infection in pregnant women due to a decline in antibody levels. [Formula presented] [Formula presented]

6.
Open Forum Infectious Diseases ; 8(SUPPL 1):S16-S17, 2021.
Article in English | EMBASE | ID: covidwho-1746815

ABSTRACT

Background. mRNA vaccines for coronavirus disease 2019 (COVID-19) illicit strong humoral and cellular responses and have high efficacy for preventing and reducing the risk of severe illness from COVID-19. Since solid organ transplant (SOT) recipients were excluded from the phase 3 trials, the efficacy of the COVID-19 vaccine remains unknown. Understanding the serological responses to COVID vaccines among SOT recipients is essential to better understand vaccine protection for this vulnerable population. Methods. In this prospective cohort study, a subset of SOT recipients who were part of our center's larger antibody study were enrolled prior to receipt of two doses of the BNT162b2 (Pfizer, Inc) vaccine for high resolution immunophenotyping. To date, plasma has been collected for 10 participants on the day of their first dose (baseline), day of their second dose, and 28 days post second dose. 23 healthy participants planning to receive either BNT162b2 or mRNA-1273 (ModernaTX, Inc) were also enrolled, providing plasma at the same timepoints. Ultrasensitive single-molecule array (Simoa) assays were used to detect SARS-CoV-2 Spike (S), S1, receptor-binding domain (RBD) and Nucleocapsid (N) IgG antibodies. Results. Participant demographics and SOT recipient characteristics are summarized in Table 1. Low titers of anti-N IgG at all timepoints indicate no natural infection with COVID-19 during the study (Fig 1A). There were significantly lower magnitudes for anti-S (p< 0.0001), anti-S1 (p< 0.0001), and anti-RBD (p< 0.0001) IgG titers on the day of dose 2 and day 28 post second dose for SOT recipients compared to healthy controls (Fig 1B,C,D). Using the internally validated threshold of anti-S IgG >1.07 based on pre-pandemic controls, only 50% of the SOT sub-cohort responded to vaccine after series completion (Fig 2). There was a positive trend between months from transplant and anti-S IgG titer (Fig 3). Black error bars denote median and 95% CI. The dotted line on panel B denotes an internally validated cutoff of 1.07;anti-S IgG titers greater than 1.07 denote a positive response. SOT recipients further out from transplant tend to have a higher anti-S IgG response. The dotted line denotes an internally validated cutoff, with anti-S IgG titers greater than 1.07 indicating a positive response. Conclusion. SOT recipients had a significantly decreased humoral response to mRNA COVID-19 vaccines compared to the healthy cohort, with those further out from transplant more likely to respond. Further research is needed to evaluate T-cell responses and clinical efficacy to maximize the SARS-CoV-2 vaccine response among SOT recipients.

7.
Open Forum Infectious Diseases ; 8(SUPPL 1):S17-S18, 2021.
Article in English | EMBASE | ID: covidwho-1746814

ABSTRACT

Background. Allogeneic stem cell transplant (SCT) recipients are at an increased risk of poor outcomes from COVID-19. While the mRNA-1273 (Moderna) and BNT162b2 (Pfizer) COVID-19 mRNA vaccines are highly immunogenic in the general population, the immune response in SCT recipients is poorly understood. We characterized the immunogenicity and reactogenicity of COVID-19 mRNA vaccines in a cohort of SCT patients. Methods. We performed a prospective cohort study of 16 allogeneic SCT patients and 23 healthy controls. Blood samples for both cohorts were collected prior to first vaccination (baseline), at the time of second vaccination, and approximately 28 days post-second vaccination. Anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG levels were measured quantitatively from plasma using a multiplexed single molecule array (Simoa) immunoassay. Reactogenicity was captured for the SCT cohort via a self-reported post-vaccination diary for 7 days after each dose. Results. Demographics and SCT recipients' characteristics are shown in Table 1. In the SCT cohort, we observed a significantly lower anti-S (p< 0.0001), S1 (p< 0.0001), and RBD (p< 0.0001) IgG responses as compared to healthy controls, both at the time of dose 2 and 28 days post-vaccine series (Fig 1). Overall, 62.5% of SCT recipients were responders after vaccine series completion, as compared to 100% of healthy controls (Fig 2). While no patients had a reported history of COVID-19 diagnosis, 2 patients in the SCT cohort had elevated anti-S IgG levels and 1 showed elevated anti-N at baseline. 10/16 participants in the SCT cohort completed at least one post-vaccination diary. Local and systemic reactions were reported by 67% and 22% of participants, respectively, after dose 1, and 63% and 50% after dose 2 (Figure 3). All reported events were mild. Anti-Spike (A), anti-S1 (B), anti-RBD (C), and anti-nucleocapsid (D) IgG titers were measured at baseline, time of second dose, and approximately 28 days after second vaccination. IgG levels were measured quantitatively using multiplexed single molecule array (Simoa) immunoassays, and are reported as Normalized Average Enzymes per Bead (AEB). Allogeneic stem cell transplant recipients (mauve) showed significantly lower anti-S, S1, and RBD IgG responses as compared to healthy controls (mint). Low titers of anti-N IgG demonstrates no history of COVID-19 natural infection during the course of the study. 10 allogeneic stem cell transplant recipients completed at least one diary for 7 days after vaccination. Reactions after dose 1 are shown in light blue, and reactions after dose 2 are shown in dark blue. Local reactions (A) were reported by 67% (6/9) of participants after dose 1, and 63% (5/8) after dose 2. Systemic reactions (B) were reported by 22% (2/9) of participants after dose 1, and 50% (4/8) after dose 2. All reported events were mild (Grade 1). Conclusion. Among SCT recipients, mRNA COVID-19 vaccines were well-tolerated but less immunogenic than in healthy controls. Further study is warranted to better understand heterogeneous characteristics that may affect the immune response in order to optimize COVID-19 vaccination strategies for SCT recipients. Figure 2: Response Rate to COVID-19 Vaccination An internally validated threshold for responders was established using pre-pandemic sera from healthy adults. A positive antibody response was was defined as individuals with anti-Spike IgG levels above the 1.07 Normalized AEB threshold.

8.
Open Forum Infectious Diseases ; 8(SUPPL 1):S89-S91, 2021.
Article in English | EMBASE | ID: covidwho-1746775

ABSTRACT

Background. SARS-CoV-2 variants of concern (VOC) have challenged real-time reverse transcriptase polymerase chain reaction (RT-PCR) methods for the diagnosis of COVID-19. Methods. The CDC 2019-Novel Coronavirus real-time RT-PCR panel was modified to create a single-plex extraction-free proxy RT-PCR assay, VOCFast™. This assay uses the nucleocapsid N1 as well as novel primer/probe pairs to target VOC mutations in the Orf1a and spike (S) genes. For analytical validation of VOCFast, synthetic controls for the Wuhan, alpha/B.1.1.7, beta/B.1.351, and gamma/P.1 strains were tested at various concentrations. Clinical validation was performed using patient anterior nares swab and saliva specimens collected in the Denver, CO area between Nov 2020 and Feb 2021 or in March 2021. Orthogonal next-generation sequencing (NGS) was also performed. Results. Similar N1 quantification cycle (Cq) values corresponding to viral load were observed for all strains, suggesting that VOC mutations do not affect performance of the N1 primer/probe. Orf1a-mut and S1-mut primer/probes generated a stable high Cq value for the Wuhan strain. Conversely, Orf1a-mut Cq values were inversely correlated with viral load for all VOC. The S1-mut Cq was inversely correlated with viral load of the alpha strain, but did not reliably amplify beta/gamma VOC. The limit of detection was 8 copies/uL. The first set of COVID-19 patient specimens revealed no amplification using Orf1amut whereas 53% of specimens collected in Mar 2021 demonstrated amplification by Orf-1a. Orthogonal testing by the SARS-CoV-2 NGS Assay and COVID-DX software demonstrated that 12/12 alpha strains, 2/2 beta/gamma strains, and 33/33 Wuhan strains were correctly identified by VOCFast. Conclusion. The combination of the N1, Orf1a-mut, and S1-mut primers/probes in VOCFast can distinguish the Wuhan, alpha, and beta/gamma strains and it consistent with NGS results. Testing of clinical samples revealed that VOC emerged in Denver, CO in March 2021. Future work to discriminate beta, gamma, and emerging VOC is ongoing. In summary, VOCFast is an extraction-free RT-PCR assay for nasal swab and saliva specimens that can identify VOC with a turnaround time suitable for clinical testing.

9.
Open Forum Infectious Diseases ; 8(SUPPL 1):S287-S288, 2021.
Article in English | EMBASE | ID: covidwho-1746623

ABSTRACT

Background. Measuring SARS-CoV-2 antibody prevalence in spent samples at serial time points can determine seropositivity in a diverse pool of individuals to inform understanding of trends as vaccinations are implemented. Methods. Blood samples collected for clinical testing and then discarded ("spent samples") were obtained from the clinical laboratory of a medical center in Atlanta. A convenience sample of spent samples from both inpatients (medical/surgical floors, intensive care, obstetrics) and outpatients (clinics and ambulatory surgery) were collected one day per week from January-March 2021. Samples were matched to clinical data from the electronic medical record. In-house single dilution serological assays for SARSCoV-2 receptor binding domain (RBD) and nucleocapsid (N) antibodies were developed and validated using pre-pandemic and PCR-confirmed COVID-19 patient serum and plasma samples (Figure 1). ELISA optical density (OD) cutoffs for seroconversion were chosen using receiver operating characteristic analysis with areas under the curve for all four assays greater than 0.95 after 14 days post symptom onset. IgG profiles were defined as natural infection (RBD and N positive) or vaccinated (RBD positive, N negative). Single dilution serological assays for SARS-CoV-2 nucleocapsid antibodies were validated using pre-pandemic and PCR-confirmed COVID-19 patient serum and plasma samples. ELISA optical density (OD) cutoffs for seroconversion were chosen using receiver operating characteristic (ROC) analysis with areas under the curve (AUC) for all four assays greater than 0.95 after 14 days post symptom onset. Results. A total of 2406 samples were collected from 2132 unique patients. Median age was 58 years (IQR 40-70), with 766 (36%) ≥ 65 years. The majority were female (1173, 55%), and 1341 (63%) were Black. Median Elixhauser comorbidity index was 5 (IQR 2-9). 210 (9.9%) patients ever had SARS-CoV-2 detected by PCR, and 191 (9.0%) received a COVID-19 vaccine within the health system. Nearly half (1186/2406, 49.3%) of samples were collected from inpatient units, 586 (24.4%) from outpatient labs, 403 (16.8%) from the emergency department, and 231 (9.6%) from infusion centers. Overall, 17.0% had the IgG natural infection profile, while 16.2% had a vaccination profile. Prevalence estimates for IgG due to natural infection ranged from 24.0% in week 2 to 9.7% in week 5, and for IgG due to vaccine from 4.4% in week 2 to 32.0% in week 6 (Table, Figure 2). Conclusion. Estimated SARS-CoV-2 IgG seroprevalence among patients at a medical center from January-March 2021 was 17% by natural infection, and 16% by vaccination. Weekly trends likely reflect community spread and vaccine uptake.

10.
Open Forum Infectious Diseases ; 8(SUPPL 1):S326, 2021.
Article in English | EMBASE | ID: covidwho-1746545

ABSTRACT

Background. Virus-specific antibodies help to understand the prevalence of infections and the course of the immune response. Humans produce antibodies against the spike and nucleocapsid proteins of SARS-COV-2 virus. Patients with COVID-19 who recover from the infections have higher levels of antibodies to spike proteins. Our study aimed to find the levels of antibodies to spike and nucleocapsid proteins in severe COVID-19. Methods. A single center prospective study was done at Ascension St John Hospital, Detroit, MI. We included COVID-19 cases diagnosed by reverse-transcriptase polymerase-chain-reaction (RT-PCR). Quantitative measurements of plasma or serum antibodies to nucleocapsid and spike proteins were done in hospitalized patients with acute COVID-19. Using the electronic medical record, we collected data on demographic and clinical information. Results. A total 24 patients were studied. Of which, 15 patients were suffering from severe and critical COVID 19 and 9 patients were suffering from mild to moderate COVID 19. The mean age (standard deviation) of our cohort was 69 ± 10 years and 60% were males. Common comorbid conditions were hypertension, obesity, and type 2 diabetes. We also noted that severe to critical COVID 19 expressed higher level of antibody to nucleocapsid. Conclusion. These results display the seroconversion in COVID 19 patients. Our study shows antibody level remain high in severe COVID 19 patients but those are against nucleocapsid protein instead of spike protein.

11.
Open Forum Infectious Diseases ; 8(SUPPL 1):S342, 2021.
Article in English | EMBASE | ID: covidwho-1746515

ABSTRACT

Background. Understanding the disease burden of SARS- CoV-2 in young children has been challenging as the majority are asymptomatic or experience mild symptoms and were rarely tested. SARS-CoV-2 is traditionally detected through respiratory secretions but has also been reported in feces where shedding may continue for weeks after respiratory samples show resolution. We examined the prevalence of SARS-CoV-2 in already collected fecal samples from young children through the pandemic as well as associated demographic factors. Methods. As part of an ongoing longitudinal microbiome study in Northern Virginia, serial stools samples were collected from infants before and throughout the Covid-19 pandemic. Reverse transcription quantitative-PCR detecting SARS-CoV-2 nucleocapsid gene in the N1 and N2 regions was performed. Penalized logistic regression models were developed to evaluate the association between fecal positivity and potential risk factors. Results. The overall prevalence of SARS-CoV-2 in infant feces was 1.69 % (13 samples) with a prevalence at delivery, 2, 6, 12 and 24 months of 0, 0, 2.56, 1.96, and 0.85 % respectively. Fecal positivity was first detected 31 days before the reported first case of Covid-19 in Northern Virginia;prevalence rates peaked in September at 4.5% (Figure 1). Only one infant who tested positive was symptomatic with COVID-19 21 days before his stool was collected. Of the 13 positive samples, 8 reported Hispanic ethnicity and 7 reported an essential worker (Table 1). Penalized logistic regression model showed association between Hispanic ethnicity and testing positive (OR 5.04 (95% CI 1.7 - 15.0)) that remained after controlling for the presences of an essential worker (OR 4.7 (95% CI 1.6 - 14.0)). Conclusion. Prevalence of SARS- CoV-2 in infant stool correlated with the prevalence of COVID-19 during the pandemic, with higher rates in those of Hispanic ethnicity corelating with regional trends. Fecal positivity in asymptomatic infants even before quarantine restrictions supports the early but silent transmission of SARS-CoV-2. This study likely underestimates true prevalence rates as stool samples were stored without viral preservative. There are many socioeconomic factors that predispose to disease while ethnicity may be a mediating or confounding factor.

12.
Open Forum Infectious Diseases ; 8(SUPPL 1):S395-S396, 2021.
Article in English | EMBASE | ID: covidwho-1746412

ABSTRACT

Background. Patients with lymphoid malignancies are at high risk of severe COVID-19 disease and were not included in the phase 3 mRNA vaccine trials. Many patients with lymphoid malignancies receive immunosuppressive therapies, including B-cell depleting agents, that may negatively impact humoral response to vaccination. Methods. We recruited patients with lymphoid malignancies and healthy participants who planned to receive two doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). Blood was drawn at baseline, prior to second dose of vaccine, and 28 days after last vaccination. Disease characteristics and therapies were extracted from patients' electronic medical record. An ultrasensitive, single molecule array (Simoa) assay detected anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG from plasma at each timepoint. Results. 23 healthy participants and 37 patients with lymphoid malignancies were enrolled (Table 1). Low titers of anti-N (Fig 1A) demonstrate no prior exposure or acquisition of COVID-19 before vaccination or during the study. 37.8% of the lymphoid malignancy cohort responded to the vaccine, using an internally validated AEB cutoff of 1.07. A significantly higher magnitude of anti-S (p< 0.0001), anti-S1 (p< 0.0001) and anti-RBD (p< 0.0001) are present in the healthy as compared to lymphoid malignancy cohort at the second dose and day 28 post-series (Fig 1B, Fig 1C and Fig 1D). Anti-S IgG titers were compared between the healthy cohort, treatment naI&Die;ve, and treatment experienced groups (Fig 2). The treatment naI&Die;ve cohort had high titers by series completion which were not significantly different from the healthy cohort (p=0.2259), although the treatment experienced group had significantly decreased titers (p< 0.0001). Of the 20 patients who had received CD20 therapy, there was no clear correlation of anti-S IgG response with time from CD20 therapy, although most patients who received CD20 therapies within 12 months from the vaccine had no response (Figure 3). Conclusion. The vaccine-induced immune response was poor among treatment-experienced patients with lymphoid malignancies, especially among those who received CD20 therapies within 12 months.

13.
Open Forum Infectious Diseases ; 8(SUPPL 1):S396-S397, 2021.
Article in English | EMBASE | ID: covidwho-1746410

ABSTRACT

Background. Well-regulated clinical trials have shown authorized COVID-19 vaccines to be immunogenic and highly efficacious. Information about antibody responses after vaccination in real-world settings is needed. Methods. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an authorized COVID-19 vaccine in a U.S. multistate longitudinal cohort study, the COVID-19 Community Research Partnership. Participants were recruited through 12 participating healthcare systems and community outreach. Participants had periodic home-based serologic testing using either a SARSCoV-2 nucleocapsid and spike IgM/IgG lateral flow assay (63% of participants) or a SARS-CoV-2 spike IgG enzyme-linked immunosorbent assay (37% of participants). The timing and number of tests before and after vaccination varied based on participant time in study. Participants were included if they were seronegative on the last test before and had >1 test result after vaccination (some had previously been seropositive, but seroreverted). A weighted Cox regression model with right censoring was used to obtain adjusted hazard ratios for sex, age, race/ethnicity, and prior seropositivity. Time-to-event (seroconversion) was defined as time to first positive test > 4 days after vaccination;participants were censored at the date of their last available test result. Results. 13,459 participants were included and 11,722 seroconverted (Table). Median time in study was 272 days (range 31-395). Median follow-up time from vaccine to last available test was 56 days (range 1-147). Participants had a median of 3 tests (range 1-12) before and 2 tests (range 1-8) after vaccination. Based on the Kaplan-Meier method, median time to seroconversion after first COVID-19 vaccination was 35 days (interquartile range: 25-45). Likelihood of seroconversion decreased with older age (Table). Female participants, non-Hispanic Black participants, and participants who were previously seropositive were more likely to seroconvert (Table). Conclusion. All subgroups had high rates of seroconversion, with some small differences in likelihood of seroconversion between subgroups. These data demonstrate the excellent immunogenicity of COVID-19 vaccines in real-world settings in the US.

14.
Open Forum Infectious Diseases ; 8(SUPPL 1):S397, 2021.
Article in English | EMBASE | ID: covidwho-1746409

ABSTRACT

Background. Covid-19 has accelerated global demand for easily distributed vaccines. Furthermore, as variant SARS-CoV-2 strains that circumvent antibody responses emerge, cross-protective vaccines provide substantial public health benefits. Vaxart is developing a shelf stable oral tablet vaccine that incorporates both the spike (S) and the more conserved nucleocapsid (N) proteins. Vaxart's vaccine platform uses a non-replicating adenovirus and a TLR3 agonist as an adjuvant. Methods. In an open-label phase 1 clinical study, 35 healthy subjects received either a single low (1x1010 IU;n=15) or high (5x1010 IU;n=15) dose of the vaccine candidate VXA-CoV2-1 with a small cohort receiving 2 low doses. PBMCs were taken at pre- and 7 days post-vaccination and restimulated with S and N peptides from SARSCoV-2 or the 4 human endemic coronaviruses (HCoV). Cells were stained for CD4/ CD8/CD107a (surface) and IFNγ/TNFα (intracellular). Subjects that received an intramuscular (i.m.) mRNA vaccine had PBMCs taken at the same timepoints and were compared in the same assay. Results. The study's results indicate that the VXA-CoV2-1 tablet was well tolerated. The majority of subjects had an increase in S-specific anti-viral CD8+ T cell responses. 19/26 (73%) subjects had a measurable CD8+ T cell response on day 8 above baseline, on average 1.5-4.6%. In a comparator experiment with the 2 SARS-CoV-2 i.m. mRNA vaccines, VXA-CoV2-1 outperformed other vaccine candidates with a >3.5-fold increase in S specific antiviral CD8 T cell responses. T cell responses specific to the 4 endemic HCoV were increased by 0.6% in subjects given VXA-CoV2-1. Conclusion. Here we describe a room temperature stable tablet that induces SARS-CoV-2 S specific CD8 T cells of high magnitude after one dose in humans. Overall, the level of antiviral SARS-CoV-2 specific T cells, particularly IFNg-producing CD8s, induced following oral immunization with VXA-CoV2-1 are of higher magnitude than the mRNA vaccines currently in use against COVID-19. T cell responses against 4 endemic HCoV were also induced. Because T cells may be important in protecting against death and severe infection, these results suggest that VXA-CoV2-1 could be cross-protective against a wide array of emerging pandemic coronaviruses.

15.
Open Forum Infectious Diseases ; 8(SUPPL 1):S593-S594, 2021.
Article in English | EMBASE | ID: covidwho-1746334

ABSTRACT

Background. The VA Million Veteran Program (MVP) studies what factors influence Veteran health. Current procedures involve collection of venous blood at MVP enrollment sites. To examine home specimen collection options, MVP performed a pilot study comparing two blood specimen collection devices and evaluated SARSCoV-2 antibody assays to determine known COVID-19 infection or vaccination. Methods. A sub-sample of MVP Veteran participants were asked to self-collect a capillary blood specimen using the Neoteryx Mitra Clamshell (up to 120uL dried blood) or Tasso-SST (up to 200uL liquid blood) per the vendor instructions. Veterans were randomly assigned to a device prior to consent. Eligibility included 30% of Veterans with known COVID-19 diagnosis or vaccination and sampling time was variable from these events. Veterans rated their device experience and shipped collected specimens directly to an MVP laboratory. Mitra tip (4) blood was eluted in 1 mL of 0.9% normal saline for 1 hour at room temperature shaking at 300 rpm. Tasso tubes were centrifuged per vendor instructions. All samples were stored at -80°C until tested with SARS-Cov-2 antibody (Ab) assays (InBios Spike IgG, BioRad Nucleocapsid (NC) Total Ab, Abbott NC IgG, and Abbott Spike IgG II) per vendor instructions. Results. 312 MVP participants consented to the pilot (52%) of which 136 (43.6%) were sent Mitra and 176 (56.4%) were sent Tasso-SST (Table 1). Participants rated the Mitra Tasso-SST equally on average as 4.4 on a 0-5 usability scale. The Abbott IgG II assay had the highest sensitivity across both devices (87% Mitra and 98% Tasso-SST) for detecting known COVID infection and/or vaccination. The InBios IgG assay with the Tasso-SST had the best sensitivity (97%) and specificity (80%) for detecting known COVID-19 infection and/or vaccination (Table 2). Conclusion. Veterans successfully collected their own specimens and had no strong preference for either device. The Tasso-SST combined with the InBios Spike IgG assay provided the highest combination of sensitivity and specificity. Limitations included one collection device per subject, varied timing of testing, unknown infection or vaccination status among some, and Tasso collection volume and Mitra whole blood dilution may have affected comparison across assays or performance.

16.
Open Forum Infectious Diseases ; 8(SUPPL 1):S804, 2021.
Article in English | EMBASE | ID: covidwho-1746282

ABSTRACT

Background. SARS-CoV-2 vaccine efficacy (VE) against asymptomatic infection and impact on viral shedding during breakthrough infections have critical implications for pandemic control. AZD1222 (ChAdOx1 nCoV-19;2 doses, 4 weeks apart) demonstrated VE of 74.0% (95% CI 65.3, 80.5) against the primary endpoint of symptomatic RT-PCR-confirmed COVID-19 and safety in a Phase 3, 2:1 randomized, placebo-controlled study in the US, Chile and Peru (n=32,451). Here we present exploratory analyses on asymptomatic infections determined by nucleocapsid (N) seroconversion and time to viral clearance in participants with symptomatic infections determined by N seroconversion (primary data cut, March 5, 2021). Methods. N seroconversion was assessed at all scheduled and illness visits in the fully vaccinated analysis set (Table). In this analysis, symptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who attended an illness visit with ≥ 1 qualifying COVID-19 symptom and had ≥ 1 positive RT-PCR result for SARS-CoV-2. Asymptomatic infections are defined as N seroconversion ≥ 15 days post second dose in participants who did not meet the criteria for symptomatic infections. In participants with symptomatic infections, viral shedding in saliva was assessed for 28 days and cumulative incidence of viral clearance was determined. Table. AZD1222 VE against symptomatic and potentially asymptomatic SARS-CoV-2 infections as determined by N seroconversion Results. Overall, 358 participants had SARS-CoV-2 infections as determined by N seroconversion (Table). Incidences per 1000 person-years of symptomatic infections were 25.62 for AZD1222 vs 103.42 for placebo (VE 75.23%;95% CI 65.33, 82.31) and of asymptomatic infections were 51.24 vs 111.95 (VE 54.24%;95% CI 39.99, 65.10) (Table). Sensitivity analyses for N seroconversion using the primary endpoint and CDC criteria for defining symptomatic/asymptomatic status were supportive. Median time to viral clearance in saliva in participants with symptomatic infections was 11 days (AZD1222, n=52) vs 16 days (placebo, n=92) (Figure). Conclusion. AZD1222 resulted in lower yet meaningful VE against asymptomatic compared to symptomatic infections, as determined by N seroconversion, and shortened viral shedding in symptomatic SARS-CoV-2 breakthrough infections vs placebo, highlighting its potential contribution to reducing viral transmission.

17.
Current Trends in Biotechnology and Pharmacy ; 15(6):80-82, 2021.
Article in English | EMBASE | ID: covidwho-1737256

ABSTRACT

For the past year SARS-CoV-2 has affected the lives of people around the globe. Therefore, research community is continuously putting in their best efforts to find a solution to curb and cure the disease. SARS-CoV-2 is a 29.9k bp long sequence genome comprising of 25 different proteins among which spike glycoprotein plays a vital role in interaction with the host cells. Hence, majority of the scientific studies were focused towards targeting the spike region for the vaccine design against the contagious virus. Thorough study of protein-protein interaction between human and virus can help us in better understanding and management of this disease. For this purpose, an Attention gated Siamese framework is utilized from which a consensus of prominent features and contextual information is taken into account to identify the influence of protein sequences. Moreover, to obtain the pattern of interacting pairs of human and SARS-CoV-2 proteins, a transfer learning-based approach is opted from the proposed network through which we obtained an accuracy of 85%. Additionally, by using this model, we identified that there were 30, 13 and 17 human proteins interacting with spike glycoprotein, nucleocapsid and membrane respectively, having predictive interaction of above 90% for each of the interactions.

18.
Blood ; 138:4681, 2021.
Article in English | EMBASE | ID: covidwho-1736312

ABSTRACT

Background Multiple vaccines have been granted emergency use authorization by the Food and Drug Administration against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the currently available vaccines, none have been systematically studied for efficacy or toxicity in patients with immunodeficiency or with immunosuppressed states, such as B cell malignancy. The purpose of the study was to evaluate the immune response to currently available vaccines against COVID-19 in patients with hematologic and solid organ malignancies. Methods This prospective study enrolled 53 patients;12 with CLL, 10 with multiple myeloma (MM), 11 with non-Hodgkin's lymphoma (NHL) and 21 with a solid organ malignancy. Using a quantitative assay, IgG antibodies to SARS-CoV-2 Spike (S) protein, and nucleocapsid (N) protein by enzyme immunoassay were measured at baseline prior to vaccination and at 2 weeks after completion of vaccination. A fourfold increase in IgG was considered a positive response to vaccination. Through a predesigned survey, patients also self-reported side effects from each dose of vaccination. Results Seroconversion with vaccination was seen in 9/10 (90%) patients with MM, 5/12 (41.7%) patients with CLL, 6/11 (54.1%) patients with NHL, and 17/21 (80.9%) patients with solid organ malignancy. Per univariate analysis, CLL (OR 0.23, 95% CI 0.05-0.88;p= 0.033) was associated with lower odds of seroconversion while NHL (OR 0.48, 95% CI 0.12-1.8;p =0.291), MM (OR 5.33, 95% CI 0.61-46.08;p= 0.128) and solid organ malignancy (OR 2.90, 95% CI 0.79-10.64;p= 0.107) were not. Among patients with hematological malignancies, 5/13 (38.3%) patients treated with rituximab and 2/7 (28.5%) patients on immunoglobulin replacement (IgR) therapy responded to vaccination. This corresponded to reduced odds of seroconversion, 0.18 (95% CI 0.047-0.69;p = 0.013) in patients treated with rituximab and 0.14 (95% CI 0.024-0.826;p=0.030) in patients on IgR. Among patients with solid organ malignancies, treatment with chemotherapy (OR 2.05, 95% CI 0.48-8.61;p=0.320), immunotherapy (OR 4.57, 95% CI 0.52-39.9;p=0.169) or endocrine therapy (OR 1.0) did not lower odds of seroconversion with vaccination. Multivariate analysis revealed patients who received rituximab were less likely to respond to vaccination as compared to patients not previously treated with rituximab (OR 0.22, 95% CI 0.05-0.955;p=0.044). Injection site soreness was the most commonly reported side effect. The only severe side effect occurred in a patient with solid organ malignancy who developed Parsonage Turner syndrome. Conclusion Our study, to the best of our knowledge, is the first study comparing pre and post vaccination IgG titers against the SARS-CoV-2 S protein. Majority of patients with MM and solid organ malignancies, including those receiving active treatment, responded adequately to immunization. Patients with CLL appear less likely to respond to vaccination against COVID-19 as compared to patients with NHL, MM or solid organ malignancies. Previous treatment with rituximab was the most significant risk factor for suboptimal response to vaccination, regardless of underlying hematologic malignancy. These data highlight the importance of continuing risk mitigation strategies against COVID-19 in individuals with hematologic malignancy, particularly those with CLL or on treatment with rituximab. Future research is needed to investigate approaches to provide protective IgG against SARS-CoV-2 in this at-risk population. [Formula presented] Disclosures: Mustafa: Genentech: Speakers Bureau;GalaxoSmithKline: Speakers Bureau;CSL Behring: Speakers Bureau;Regeneron: Speakers Bureau;AstraZeneca: Speakers Bureau. Walsh: Janssen: Research Funding;Merck: Research Funding;Pfizer: Research Funding. Jamshed: Takeda: Honoraria.

19.
Blood ; 138:4732, 2021.
Article in English | EMBASE | ID: covidwho-1736295

ABSTRACT

mRNA vaccines BNT162b2 and mRNA1273 are highly effective in preventing SARS-CoV-2 infection and mortality in healthy adults. However, their immunogenicity in immunocompromised Multiple Myeloma (MM) patients is less clear. We performed an observational prospective study of 96 MM patients (pts) treated at our centre, aimed at assessing the humoral and cell-mediated immune (CMI) response following the full immunization schedule. To this aim, we measured serum levels of neutralizing IgG anti Spike-protein (IgG anti S-RBD) at 1, 3, 6, 9 and 12 months after the 2 nd dose of vaccination, using the electrochemiluminescence (ECLIA) platform (Elecsys® Anti-sars-Cov-2 ECLIA assay) and evaluated CMI response in terms of pts with a SARS-CoV-2 specific IFNγ T cell response by IGRA (Interferon-Gamma Release Assays) test at 3 and 12 months after 2 nd dose. A concentration level of IgG anti S-RBD ≥0.80 U/ml was considered a seropositive result. Herein, we report preliminary data on the development of humoral response in 96 MM pts who reached the first study timepoint (1 month after 2 nd dose), compared to 54 health-care workers as controls. At vaccination, the median age of the 96 patients (51 males/45 females) was 66.5 (range 47-83) years. The median number of previous lines of therapy was 1 (range 1-11) and only 7 (7.3%) pts were not receiving active treatment. 44.8% (n=43) pts had relapse/refractory MM. Among 72 (75%) transplant-eligible pts, 63 patients had previously received autologous stem-cell transplantation (ASCT) with a median time between ASCT and vaccine of 31 (range 3-274) months. 70 (72.9%) pts had received immunomodulatory drugs (IMIDs) containing regimens, 30 (31.3%) proteasome inhibitors (PIs), 11 (11.5%) IMIDs + PIs, 32 (33.3%) anti-CD38 monoclonal antibodies (anti-CD38 moAbs). 33 (34.4%) pts were in lenalidomide (R) maintenance therapy. At vaccination, 67 (68.8%) pts were in VGPR or higher, 18 (18.7%) in PR and 11 (11.3%) in SD or PD. Immunoparesis (≥1 uninvolved Ig below lower level limit) was observed in 78 (88.6%) pts, of whom 59 (67.1%) showed a reduction of two Ig classes. All pts had completed the 2 planned doses of BNT162b2 (40.6%) or mRNA1273 (59.4%) vaccine 3 or 4 weeks apart, respectively. Control cohort (n=54;median age of 51 [range 40-66] years) received mRNA vaccine during the same period. People with previous SARS-CoV-2 infection (positive IgG anti S-RBD or anti-nucleocapsid N antibody titer before vaccines) were excluded from the analysis. At 1 month post 2 nd dose, (median 30 days, IQR 28-32) seropositive response rate to vaccination was 91.7% (n=88) for MM pts vs 100% for controls, p=0.05;the median IgG anti S-RBD titer was 435 (range 0.4-2500) vs 1040.5 U/ml (range 160-2500), respectively;p=0.008. No difference in the rate of seropositive response between those who received the 2 type of vaccines was found (p=0.09). Pts with response level ≥ CR had a median antibody (Ab) titer (1242 U/ml, range 0.4-2500) significantly higher than those with ≤CR (221.5 U/ml, range 0.4- 2500), p<0.001. Pts receiving PI (median Ab titer 156;range 0.4- 2500) and anti-CD38 MoAbs (median titer 265 U/ml;0.4- 2500) containing regimens had a lower Ab titer than all the other pts (p=0.003 and p<0.001, respectively). Median Ab titer was higher in pts who received ASCT vs others (1042, range 0.4- 2500 vs 160 U/ml, range 228-2500, p<0.001) and in pts receiving R maintenance (1681.2, range 0.4-2500 vs 529.5 U/ml, range 0.4-2500, p<0.001). In pts with 2-Ig immunoparesis, the median Ab titer was 272 (range 0.4-2500) vs 2500 U/ml (range 228-2500) for no immunoparesis (p= 0.0037). A distribution analysis of the Ab titer revealed a significant correlation between better humoral response and hematological response ≥ CR (p<0.001), being in first-line treatment (p=0.039), having received ASCT (p=0.001) and receiving R maintenance (p=0.001). Multivariate analysis confirmed ≥ CR [OR 2.54, 95% CI 93-756], being in first line treatment [OR 2.10, CI 22-722] and R maintenance therapy [OR 4.53, CI 484-1233] as independen predictors of better humoral response at 1 month after 2 nd vaccine dose. In conclusion, mRNA vaccines provided a high seropositivity rate in pts in active MM treatment, with a better humoral response in pts achieving CR, those who received ASCT and receiving R maintenance. Immunoparesis was confirmed to be an unfavourable factor for the development of humoral response, as well as treatment with anti-CD-38 moAbs. Disclosures: Mancuso: Celgene: Honoraria;Takeda: Honoraria;Sanofi: Honoraria;Amgen: Honoraria;Janssen: Honoraria. Zamagni: Takeda: Honoraria;Amgen: Honoraria;Bristol-Myers-Squibb: Honoraria;Janssen: Honoraria. Pantani: Amgen: Honoraria;Janssen: Honoraria. Rocchi: Amgen: Honoraria;GalxoSmithKline: Honoraria;Janssen: Honoraria. Rizzello: Amgen: Honoraria;GlaxoSmithKline: Honoraria;Sanofi: Honoraria. Tacchetti: Amgen: Honoraria;BMS/Celgene: Honoraria;Janssen: Honoraria;Takeda: Honoraria;AbbVie: Honoraria;Sanofi: Honoraria;GlaxoSmithKline: Honoraria;Oncopeptides: Honoraria. Zinzani: JANSSEN-CILAG: Other: Advisory board, Speakers Bureau;MSD: Consultancy, Other: Advisory board, Speakers Bureau;SANDOZ: Other: Advisory board;TG Therapeutics: Other: Advisory board, Speakers Bureau;GILEAD: Other: Advisory board, Speakers Bureau;SERVIER: Other: Advisory board, Speakers Bureau;BMS: Other: Advisory board, Speakers Bureau;CELLTRION: Other: Advisory board, Speakers Bureau;TAKEDA: Other: Advisory board, Speakers Bureau;ROCHE: Other, Speakers Bureau;EUSAPHARMA: Consultancy, Other, Speakers Bureau;KYOWA KIRIN: Other, Speakers Bureau;Incyte: Other, Speakers Bureau;NOVARTIS: Consultancy, Other, Speakers Bureau;ADC Therap.: Other;Beigene: Other, Speakers Bureau;VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Cavo: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau;AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Consultancy, Honoraria;Novartis: Honoraria;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;GlaxoSmithKline: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

20.
Digestive and Liver Disease ; 54:S1, 2022.
Article in English | EMBASE | ID: covidwho-1734329

ABSTRACT

Background and Aims: SARS-CoV-2 mRNA vaccines have been approved to prevent COVID-19. We assessed immunogenicity, effectiveness and safety of vaccines in patients with compensated and decompesated cirrhosis. Method: This is a prospective single center study assessing humoral and cellular responses in cirrhotics compared to healthy controls, incidence post-vaccination SARS-CoV-2 infections and adverse events (AEs). Antibodies against the spike- and nucleocapside-protein (anti-S and anti-N) were tested at baseline, 21 days after the first and second doses and during follow-up. Spike-specific T-cells quantity assessment was longitudinally conducted by the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by IFN-γ and IL-2 measurement. Results: 182 cirrhotics (61 years, 75% males, 45% viral-related, 74% Child-Pugh A, 31% HCC, 85% COVID-19 naïve) and 38 healthy subjects were enrolled. Previous SARS-CoV-2 infection predicted higher anti-S titres at all time points after vaccination, in both groups. COVID-19 naïve cirrhotics showed significantly lower anti-S titres compared to controls [998.5 (0.4-12,500) vs 1,520 (259-12,500) U/mL, p=0.048], anti-S titres significantly decreased after a median of 133 (70-182) days [536 (0.4-8,777) U/mL, p<0.0001] and were lower in decompensated vs compensated cirrhosis [632 (0.4-12,500) vs 1,377 (0.4-12,500) U/mL, p=0.028]. By multivariable analysis in COVID-19 naïve cirrhotics, independent predictors of lower anti-S were active HCC, immunocompromised conditions, BNT162b2 and lower anti-S after first dose. The spike-specific T-cell response was evaluated in 14 cirrhotics, showing a heterogeneous magnitude of response, but on average the quantity and kinetics of decline of the spike-specific cellular responses diverged in cirrhotics compared to controls, with lower concentrations of both IFN-γ and IL-2. During follow-up, 4/133 (3%) COVID-19 naïve cirrhotics tested positive for anti-N, all asymptomatic. Neither unexpected nor severe AEs emerged. Conclusion: Humoral and cellular responses to SARS-CoV-2 mRNA vaccines appeared suboptimal in patients with cirrhosis, however the rate of post-vaccination infection seems low.

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