scholarly journals Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenji Maeda ◽  
Masayuki Amano ◽  
Yukari Uemura ◽  
Kiyoto Tsuchiya ◽  
Tomoko Matsushima ◽  
...  

AbstractWhile mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.

2021 ◽  
Author(s):  
Kenji Maeda ◽  
Masayuki Amano ◽  
Yukari Uemura ◽  
Kiyoto Tsuchiya ◽  
Tomoko Matsushima ◽  
...  

Abstract While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of serums against variants of concerns was determined. Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of NT50s was ~ 68 days and the estimated average time length till the total disappearance of neutralizing activity was ~ 198 days. While serums from elite-responders (NT50s > 1,500-fold: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some serums with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.


2021 ◽  
Author(s):  
Kenji Maeda ◽  
Masayuki Amano ◽  
Yukari Uemura ◽  
Kiyoto Tsuchiya ◽  
Tomoko Matsushima ◽  
...  

Background: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified. Methods: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined. Findings: Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation was seen between NT50s and AEs. NT50s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT50s>1,500-fold: the top 4% among all participants' NT50s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain. Interpretation: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed.


Author(s):  
Sabha Mushtaq ◽  
Erdinc Terzi ◽  
Sebastiano Recalcati ◽  
Julio C. Salas‐Alanis ◽  
Sanober Amin ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenji Maeda ◽  
Nobuyo Higashi-Kuwata ◽  
Noriko Kinoshita ◽  
Satoshi Kutsuna ◽  
Kiyoto Tsuchiya ◽  
...  

AbstractWhile there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1347
Author(s):  
Claudia Maria Trombetta ◽  
Serena Marchi ◽  
Simonetta Viviani ◽  
Alessandro Manenti ◽  
Linda Benincasa ◽  
...  

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044168
Author(s):  
Prahlad Adhikari ◽  
Asish Subedi ◽  
Birendra Prasad Sah ◽  
Krishna Pokharel

ObjectivesThis study aimed to determine if low dose intravenous ketamine is effective in reducing opioid use and pain after non-elective caesarean delivery.DesignProspective, randomised, double-blind.SettingTertiary hospital, Bisheshwar Prasad Koirala Institute of Health Sciences, Dharan, NepalParticipants80 patients undergoing non-elective caesarean section with spinal anaesthesia.InterventionsPatients were allocated in 1:1 ratio to receive either intravenous ketamine 0.25 mg/kg or normal saline before the skin incision.Primary and secondary outcome measuresThe primary outcome was the total amount of morphine equivalents needed up to postoperative 24 hours. Secondary outcome measures were postoperative pain scores, time to the first perception of pain, maternal adverse effects (nausea, vomiting, hypotension, shivering, diplopia, nystagmus, hallucination) and neonatal Apgar score at 1 and 5 min, neonatal respiratory depression and neonatal intensive-care referral.ResultsThe median (range) cumulative morphine consumption during the first 24 hours of surgery was 0 (0–4.67) mg in ketamine group and 1 (0–6) mg in saline group (p=0.003). The median (range) time to the first perception of pain was 6 (1–12) hours and 2 (0.5–6) hours in ketamine and saline group, respectively (p<0.001). A significant reduction in postoperative pain scores was observed only at 2 hours and 6 hours in the ketamine group compared with placebo group (p<0.05). Maternal adverse effects and neonatal outcomes were comparable between the two groups.ConclusionsIntravenous administration of low dose ketamine before surgical incision significantly reduced the opioid requirement in the first 24 hours in patients undergoing non-elective caesarean delivery.Trial registration numberNCT03450499.


2021 ◽  
Author(s):  
Amy J. Schuh ◽  
Panayampalli S. Satheshkumar ◽  
Stephanie Dietz ◽  
Lara Bull-Otterson ◽  
Myrna Charles ◽  
...  

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.


2013 ◽  
Vol 28 (6) ◽  
pp. 340-343 ◽  
Author(s):  
T. Fischel ◽  
A. Krivoy ◽  
M. Kotlarov ◽  
Z. Zemishlany ◽  
O. Loebstein ◽  
...  

AbstractBackground:Discontinuation of antipsychotic drugs in schizophrenia patients is a major concern, since it results in relapse and re-hospitalizations. Non-adherence is strongly associated with negative-subjective response to antipsychotics, which is composed of the subjective experience of negative drug effects and attitude towards the treatment.Objective:To investigate the elements of subjective experience and subjective attitude towards specific drug-related adverse effects, leading to a generally negative-subjective attitude towards antipsychotics.Methods:Schizophrenia inpatients (n = 84) were administered a questionnaire measuring attitude and experience on eight subscales: weight gain, sedation, sexual anhedonia, extra-pyramidal syndrome, affective flattening, excessive sleep, diminished sociability and metabolic syndrome. DAI-30 was used to measure attitude towards drugs, and PANSS to assess psychopathology.Results:Weak correlation was found between subjective experience and attitude on most of the subscales. The only strong, albeit inverse, correlation between experience and attitude that was found was with regard to affective flattening, experienced by 37% of the sample, and it also predicted negative drug attitude as measured by the DAI-30, RR: 1.87 (95% CI: 1.06–3.3, df = 1, χ2 = 4.525, P < 0.05).Conclusion:Negative attitude towards most adverse drug effects did not correlate with personal experience. Drug-related affective flattening should be evaluated routinely, since experiencing it may predict negative attitude towards drugs, potentially leading to poor compliance and relapse.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mohamed A. Ghanem

Abstract Background Interrupted cyclic treatment with a low oral dose of prednisolone combined with stepladder analgesics would reduce the pain scores in cancer patients with reported less side effects. Following ethical approval, 39 cancer patients were randomized to receive prednisolone 10 mg every other day or every 4th day for 4 successive weeks followed with tapering prednisolone by 2.5 mg every 4 days over 2 weeks after each interval, primary outcome visual analog score (VAS), and other secondary outcomes such as (A) patient demographics; (B) pain scores; brief pain inventory score (BPI), pain severity score (PSS), pain interference score (PIS), analgesia level score, pain level score (PLS), and pain management index (PMI)); and (C) patient safety (adverse effects) with interrupted cyclic treatment with low-dose prednisolone. Results Compared with baseline values, patients had statistically significant lower VAS and PSS pain scores at 14 and 28 days after starting the 2 days cyclic treatment with prednisolone. Patients had comparative VAS and PSS pain scores during the 4-day cyclic treatment with prednisolone. Compared with the 4-day cyclic treatment, patients in the 2-day cyclic treatment had significant statistically lower VAS pain scores at 28 days. Adverse effects showed no significant statistical differences during both study sequences. Conclusion Interrupted cyclic prednisolone 10 mg combined with stepladder analgesic regimen is effective and safe in terms on improved quality of analgesia for 28 days in cancer patients more when used every 2nd day than every 4th day with appetite improvement during both. Trial registration The study protocol was approved by the local Institutional Board Review Committee on 8-11-2019. The study was prospectively registered with the www.clinicaltrials.gov


2021 ◽  
Author(s):  
Kenji Maeda ◽  
Masayuki Amano ◽  
Yukari Uemura ◽  
Kiyoto Tsuchiya ◽  
Tomoko Matsushima ◽  
...  

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