scholarly journals Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders

Author(s):  
Douglas F. Lake ◽  
Alexa J. Roeder ◽  
Maria J. Gonzalez-Moa ◽  
Megan Koehler ◽  
Erin Kaleta ◽  
...  

ABSTRACTObjectiveTo determine if poor responders to COVID-19 RNA vaccines (<50% neutralisation) after two doses would remain poor responders, or if a third dose could elicit high levels of NAbs.DesignClinical follow-up studySettingAcademic and medical institutions in USAParticipants269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines.Main Outcome MeasuresNAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose.ResultsIn 269 study participants, percent neutralisation ranged from 0% to 99% 2-4 weeks after a second vaccine dose. The majority of vaccine recipients (154/269, 57%) demonstrated NAb levels at ≥75% 2-4 weeks after their second dose. Our study also revealed that 25% of vaccine recipients did not neutralise above 50% (Median neutralisation = 21%, titers <1:80) within a month after their second dose. We called these individuals “vaccine poor responders” (VPRs). Twenty-three VPRs ranging in age from 31 to 79 (10 males, 13 females, average age = 62.5) independently obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, poor responders showed an average 20-fold increase in NAb levels (range 46%-99%).ConclusionsThe results suggest that poor responders are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose–independent of mRNA vaccine manufacturer. Previous reports indicate that NAb levels decline much more rapidly than clinical protection from hospitalisation and disease, but that does not account for vaccine recipients who never generated high levels of NAbs after two doses. It is possible that poor responders are a source of breakthrough infections. Although it is not known what levels of NAbs protect from infection or disease, many vaccine recipients in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, asymptomatic viral replication, and potential transmission.

2021 ◽  
Author(s):  
Douglas Lake ◽  
Alexa Roeder ◽  
Maria Gonzalez-Moa ◽  
Megan Koehler ◽  
Erin Kaleta ◽  
...  

Abstract Background While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of RNA vaccine recipients did not neutralize >50%. We termed this group “vaccine poor responders” (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs. Methods 269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines were evaluated. NAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose. Results Analysis of vaccine recipients revealed that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs showed an average 20-fold increase in NAb levels (range: 46%-99%). Conclusions The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission.


2021 ◽  
Author(s):  
Kevin K. Arien ◽  
Leo Heyndrickx ◽  
Johan Michiels ◽  
Katleen Vereecken ◽  
Kurt Van Lent ◽  
...  

We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in healthy individuals pre-infected or not with SARS-CoV-2 and immunized with three doses of the BNT162b2 vaccine. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.


2021 ◽  
Vol 8 ◽  
Author(s):  
André Weigert ◽  
Marie-Louise Bergman ◽  
Lígia A. Gonçalves ◽  
Iolanda Godinho ◽  
Nádia Duarte ◽  
...  

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in &gt;30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p &lt; 2.2 × 10−16).Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.


Author(s):  
Göran Friman

Objective: To describe the distribution of risk, diagnosis and pharmacological treatments for diabetes and hypertension after seven years among patients provided with opportunistic medical screening in a dental setting. Material and Methods: The initial screening’s 170 participants were asked to take part in a seven-year follow-up study. Data were collected through self-reported information in a written health declaration. Outcome measures: • Number of study participants who had passed away • Prescription of antidiabetics or antihypertensives • Changes in weight and height to calculate body mass index (BMI) Results: The follow-up study consisted of 151 participants. Twenty had passed away. The risk needs for medicating with antihypertensive drugs after seven years for those not receiving pharmacological treatment at the initial screening was 3.7 times greater (p=0.025 CI 1.2-11.3) for participants with a diastolic blood pressure (BP) ≥ 90 mm Hg (85 for diabetics) than for the others. The risk was 3.9 times greater (p=0.020 CI 1.2-12.6) for those with a systolic BP of 140-159 mm Hg and 54.2 times greater (p<0.0001 CI 9.8-300.3) for those with a systolic BP ≥ 160 mm Hg than for those with a systolic BP 140 mm Hg. There were no changes in BMI. Conclusion: At least one in ten cases of incorrect medication or undiagnosed hypertension may be identifiable through opportunistic medical screening


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 813
Author(s):  
Michele Manganelli ◽  
Ilaria Grossi ◽  
Manuela Ferracin ◽  
Paola Guerriero ◽  
Massimo Negrini ◽  
...  

Human hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver and the third cause of cancer-related deaths. The multikinase inhibitor sorafenib is a systemic drug for unresectable HCC. The identification of molecular biomarkers for the early diagnosis of HCC and responsiveness to treatment are needed. In this work, we performed an exploratory study to investigate the longitudinal levels of cell-free long ncRNA GAS5 and microRNAs miR-126-3p and -23b-3p in a cohort of 7 patients during the period of treatment with sorafenib. We used qPCR to measure the amounts of GAS5 and miR-126-3p and droplet digital PCR (ddPCR) to measure the levels of miR-23b-3p. Patients treated with sorafenib displayed variable levels of GAS5, miR-126-3p and miR-23b-3p at different time-points of follow-up. miR-23b-3p was further measured by ddPCR in 37 healthy individuals and 25 untreated HCC patients. The amount of miR-23b-3p in the plasma of untreated HCC patients was significantly downregulated if compared to healthy individuals. The ROC curve analysis underlined its diagnostic relevance. In conclusion, our results highlight a potential clinical significance of circulating miR-23b-3p and an exploratory observation on the longitudinal plasmatic levels of GAS5, miR-126-3p and miR-23b-3p during sorafenib treatment.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Maria Elena Flacco ◽  
Graziella Soldato ◽  
Cecilia Acuti Martellucci ◽  
Roberto Carota ◽  
Rossano Di Luzio ◽  
...  

This retrospective cohort study compared the rates of virologically-confirmed SARS-CoV-2 infections, symptomatic or lethal COVID-19 among the residents of the Italian province of Pescara who received one or two doses of COVID-19 vaccines, versus the unvaccinated. The official data of the National Health System were used, and a total of 69,539 vaccinated adults were compared with 175,687 unvaccinated. Among the subjects who received at least one vaccine dose, 85 infections (0.12%), 18 severe and 3 lethal COVID-19 cases were recorded after an average follow-up of 38 days. Among the unvaccinated, the numbers were 6948 (4.00%), 933 (0.53%) and 241 (0.14%), respectively. The serious adverse event reports—yet unconfirmed—were 24 out of 102,394 administered doses. In a Cox model, adjusting for age, gender, and selected comorbidities, the effectiveness of either BNT162b2, ChAdOx1 nCoV-19 or mRNA-1273 vaccines was higher than 95% in preventing infections (mostly due to B.1.1.7 variant), symptomatic or lethal COVID-19. No differences were observed across genders, and among the 691 subjects who received the second dose of vaccine later than the recommended date. Although preliminary, these findings support current immunization policies and may help reducing vaccine hesitancy.


2021 ◽  
pp. 136787792110035
Author(s):  
Mari Lehto ◽  
Susanna Paasonen

This article investigates the affective power of social media by analysing everyday encounters with parenting content among mothers. Drawing on data composed of diaries of social media use and follow-up interviews with six women, we ask how our study participants make sense of their experiences of parenting content and the affective intensities connected to it. Despite the negativity involved in reading and participating in parenting discussions, the participants find themselves wanting to maintain the very connections that irritate them, or even evoke a sense of failure, as these also yield pleasure, joy and recognition. We suggest that the ambiguities addressed in our research data speak of something broader than the specific experiences of the women in question. We argue that they point to the necessity of focusing on, and working through affective ambiguity in social media research in order to gain fuller understanding the complex appeal of platforms and exchanges.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chi Zhang ◽  
Li Li ◽  
Shiping Cheng ◽  
Debajyoti Chowdhury ◽  
Yong Tan ◽  
...  

Abstract Background Hypertension (HTN) patients who have phlegm-dampness syndrome (PDS) tend to be obese and have worse outcomes. However, the association of body weight (BW) changes and mechanisms underlying the pathophysiology of HTN-PDS are not well elucidated. This study aims to identify the longitudinal observations associated with the circulating markers discriminating BW changes of individuals with HTN-PDS. Methods An integrative approach relying on metabolomics and proteomics was applied to serum samples from HTN-PDS patients in a prospective cohort to identify the plausible mechanistic pathways underpinning HTN-PDS pathophysiology. Study participants were determined to have experienced a weight change if they showed a 5%–15% increase/reduction in BW at the end of the follow-up period. The joint pathway analysis and network analysis were performed using Ingenuity Pathway Analysis (IPA®) on the serum samples obtained from the participants over the period. Results The study involved 22 HTN-PDS patients who were overweight initially and were able to lose enough weight and 24 HTN-PDS individuals who developed overweight from normal BMI during a one-year follow-up. Our analysis suggested three types of phosphatidylcholine (PC) were altered. PC (22:2(13Z,16Z)/24:1(15Z)) and LysoPC (16:1(9Z)) were decreased in Queryweight gain samples, whereas the levels of PC (14:0/16:0) were increased in weight loss samples. The metabolomic analysis suggested 24 metabolites associated with HTN-PDS. Of them, 13 were up-regulated and 11 were down-regulated. The two-dimensional difference gel electrophoresis (2D DIGE) identified 45 phosphorylated proteins got altered in the HTN-PDS patients, wherein 23 were up-regulated and 22 were down-regulated. Integrated proteomic and metabolomics analyse acknowledged biomarkers PC, Complement C3, C4a/C4b, A2M and SERPINF1 as strong predictors for BW changes in HTN-PDS patients. Conclusion The combined serum proteomic and metabolomic profiling reveals a link between BW change and the complement system activity, altered phosphatidylcholine metabolism in HTN-PDS patients. Future studies with larger cohorts are required to strengthen and validate these findings.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 770-770
Author(s):  
Bonnielin Swenor ◽  
Aleksandra Mihailovic ◽  
Pradeep Ramulu

Abstract The home environment and features of the home have been identified as important risk factors for falls, and may pose particular risk for older adults with visual impairments given difficulty with hazard perception. We used data from 245 participants in the Falls in Glaucoma Study [mean age: 71 years, mean follow-up: 31 months] with homes graded using our previously validated Home Environment Assessment for the Visually Impaired (HEAVI), which quantifies the number of in-home fall-related hazards and found that neither the number of hazards nor the percentage of hazardous items were associated falls/year. However, each 10-fold increase in lighting was associated with a 35% lower rate of falls/year (RR=0.65, 95%CI=0.46 to 0.92) and there was a 50% reduction in falls/year when lighting was at or above 30 footcandles (minimum lighting level recommended by the Engineering Society of North America) compared to lighting &lt;30 footcandles (RR=0.50, 95%CI=0.26 to 0.96).


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jaana Keto ◽  
Sonja Hahtola ◽  
Miika Linna ◽  
Liisa Väkevä

Abstract Background Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting. Methods In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998–2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland. Results The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998–2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up. Conclusions The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998–2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.


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