Effect of SARS-CoV-2 Vaccination on Symptoms from Post-Acute Sequelae of COVID-19: Results from the Nationwide VAXILONG Study

Introduction: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC). Patients and methods: We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied. Results: 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents’ median age was 44 (IQR 25–75: 37–50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198–431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). Conclusion: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC.

Parental preferences for a mandatory vaccination scheme in England; a discrete choice experiment

Background: Mandatory vaccination has been mooted to combat falling childhood vaccine uptake rates in England. This study investigated parental preferences for a mandatory vaccination scheme. Methods: Discrete choice experiment. Six attributes were investigated: vaccine (MMR, 6-in-1), child age group (2 years and older, 5 years and older), incentive (130 GBP cash incentive for parent, 130 GBP voucher incentive for child, no incentive), penalty (450 GBP fine, parent not able to claim Child Benefits for an unvaccinated child, unvaccinated child not able to attend school or day care), ability to opt out (medical exemption only, medical and religious belief exemption), and compensation scheme (not offered, offered). Mixed effects conditional logit regression models were used to investigate parental preferences and relative importance of attributes. Findings: Participants were 1,001 parents of children aged 5 years and under (53% female, mean age=33.6 years, SD=7.1, 84% white British). Parental preferences were mostly based on incentives (slight preference for cash pay-out for the parent versus a voucher for the child) and penalties (preference for schemes that did not allow unvaccinated children to attend school or day care and those that withheld financial benefits for parents of unvaccinated children). Parents also preferred schemes that: offered a compensation scheme, mandated the 6-in-1 vaccine, mandated vaccination in children aged 2 years and older, and that offered only medical exemptions. Interpretation: Results can inform policymakers' decisions about how best to implement a mandatory childhood vaccination scheme in England. Funding: Data collection was funded by a British Academy/Leverhulme Small Research Grants (SRG1920\101118).

CHANGES IN THE BIOCHEMICAL PARAMETERS OF THE BLOOD OF DAIRY COWS WHEN USING THE VACCINE "KLOSTBOVAK-8" IN COMBINATION WITH THE IMMUNOMODULATOR "MIXOFERON"

The relevance of this topic is determined by the need in the conditions of agricultural enterprises to develop the most effective vaccination scheme against diseases caused by Clostridia. This article presents the results of a study, the purpose of which was to study the effect of the immunomodulator "Mixoferon" in conjunction with the use of the vaccine "Klostbovak-8" on the biochemical and immunological parameters of the blood.

Effect of SARS-CoV-2 vaccination on symptoms from post-acute COVID syndrome: results from the national VAXILONG survey

Introduction: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute COVID-19 syndrome (PACS). Patients and methods: We conducted a nationwide online survey among adult patients with PACS as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PACS symptoms, vaccine type and scheme and its effect on PACS symptoms were studied. Results: Six hundred and twenty surveys were completed and 567 satisfied the inclusion criteria and were analyzed. Respondents were 83.4% of women of median age 44 (IQR 25-75: 37-50). Initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 [198-431] days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported variation of symptoms following the injection, without difference based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. 170 PACS patients had not been vaccinated. The most common reasons for postponing SARS-CoV-2 vaccine were a fear of worsening PACS symptoms (55.9%) and the idea that vaccination was contraindicated because of PACS (15.6%). Conclusion: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PACS patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increase vaccine coverage in patients with PACS.

mRNA vaccines effectiveness against COVID-19 hospitalizations and deaths in older adults: a cohort study based on data-linkage of national health registries in Portugal

Background: We used electronic health registries to estimate the mRNA vaccine effectiveness (VE) against COVID-19 hospitalizations and deaths in older adults. Methods: We established a cohort of individuals aged 65 and more years, resident in Portugal mainland through data linkage of eight national health registries. For each outcome, VE was computed as one minus the confounder-adjusted hazard ratio, estimated by time-dependent Cox regression. Results: VE against COVID-19 hospitalization ≥14 days after the second dose was 94% (95%CI 88 to 97) for age-group 65-79 years old (yo) and 82% (95%CI 72 to 89) for ≥80 yo. VE against COVID-19 related deaths ≥ 14 days after second dose was 96% (95%CI 92 to 98) for age-group 65-79 yo and 81% (95%CI 74 to 87), for ≥80 yo individuals. No evidence of VE waning was observed after 98 days of second dose uptake. Conclusions: mRNA vaccine effectiveness was high for the prevention of hospitalizations and deaths in age-group 65-79 yo and ≥80 yo with a complete vaccination scheme, even after 98 days of second dose uptake.

Heterologous immunisation with vector vaccine as prime followed by mRNA vaccine as boost leads to humoral immune response against SARS-CoV-2, which is comparable to that according to a homologous mRNA vaccination scheme

Background: The humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (BioNTech, BNT162b2; Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2). Methods: Sera from 59 vaccinees were tested for SARS-CoV-2 immunoglobulin G (IgG) and virus-neutralising antibodies (VNA) with four IgG assays, a surrogate neutralisation test (sVNT) and a Vero cell-based neutralisation test (cVNT) before and after heterologous (n=31 and 42) or homologous booster vaccination (AZD1222/AZD1222, n=8/9; BNT162b2/BNT162b2, n=8/8). The strength of IgG binding to separate SARS-CoV-2 antigens was measured as avidity. Results: After the first vaccination, prevalence of IgGs antibodies directed against (trimeric) SARS-CoV-2 spike (S)- protein and its receptor-binding domain (RBD) varied from 55-95 % (AZD1222) to 100% (BNT162b2), depending on the vaccine used and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100 percent seroconversion and appearance of highly avid IgG as well as VNA against a SARS-CoV-2 variant of concern (alpha; B.1.1.7) used as antigen in the cVNT. The results of the sVNT basically agree with those of our in-house cVNT, but the sVNT seems to overestimate non- and weakly virus-neutralizing titres. The mean IgG and VNA titres were higher after heterologous vaccination compared to the homologous AZD1222 scheme. Conclusions: The heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespectively of the chosen immunisation regime, highly avid IgG antibodies can be detected just two weeks after the second vaccine dose indicating the development of a robust humoral immunity.

Heterologous prime-boost vaccination with ChAdOx1 nCoV-19 and BNT162b2 mRNA

Administration of a first dose of the COVID-19 vaccine ChAdOx1 nCoV-19 (Vaxzevria®, AstraZeneca) is associated with a certain risk for vaccine-induced immune thrombotic thrombocytopenia. Therefore, several countries have recommended replacing the second dose of ChAdOx1 nCoV-19 with an mRNA-based vaccine as a precautionary measure, although data on safety and efficacy of such heterologous prime-boost regimen are sparse. Therefore, vaccinees, who had received a heterologous vaccination using ChAdOx1 nCoV-19 as prime and BNT162b2 (Comirnaty®, BioNTech-Pfizer) mRNA as boost vaccination were offered SARS-CoV-2 antibody testing to quantify their vaccine-induced neutralizing antibody response. The results were compared to cohorts of healthcare workers or volunteers, who received homologous BNT162b2 or homologous ChAdOx1 nCoV-19 vaccination regimens, respectively. A striking increase of vaccine-induced SARS-CoV-2 neutralizing antibody activity was observed in 229 vaccinees that received a BNT162b2 boost 9 to 12 weeks after ChAdOx1 nCoV-19 prime. In our cohort comprising over 480 individuals, the heterologous vaccination scheme induced significantly higher neutralizing antibody titers than homologous ChAdOx1 nCoV-19 and even than homologous BNT162b2 vaccination. This proves that a single dose of a COVID-19 mRNA vaccine after ChAdOx1 nCoV-19 prime vaccination is sufficient to achieve high neutralizing antibody levels predicting immune protection from SARS-CoV-2 infection, and may even increase vaccine efficacy offering an alternative in a setting of vaccine shortage.

Will the Large-scale Vaccination Succeed in Containing the COVID-19 Epidemic and How Soon?

The availability of vaccines provides a promising solution to containing the COVID-19 pandemic. Here, we develop an epidemiological model to quantitatively analyze and predict the epidemic dynamics of COVID-19 under vaccination. The model is applied to the daily released numbers of confirmed cases of Israel and United States of America to explore and predict the trend under vaccination based on their current epidemic status and intervention measures. For Israel, of which 53.83% of the population was fully vaccinated, under the current intensity of NPIs and vaccination scheme, the pandemic is predicted to end between May 14, 2021 to May 16, 2021 depending on an immunity duration between 180 days and 365 days; Assuming no NPIs after March 24, 2021, the pandemic will ends later, between July 4, 2021 to August 26, 2021. For USA, if we assume the current vaccination rate (0.268% per day) and intensity of NPIs, the pandemic will end between February 3, 2022 and August 17, 2029 depending on an immunity duration between 180 days and 365 days. However, assuming an immunity duration of 180 days and with no NPIs, the pandemic will not end, and instead reach an equilibrium state with a proportion of the population remaining actively infected. Overall the daily vaccination rate should be chosen according to the vaccine efficacy and the immunity duration to achieve herd immunity. In some situations, vaccination alone cannot stop the pandemic, and NPIs are necessary both to supplement vaccination and accelerate the end of the pandemic. Considering that vaccine efficacy and duration of immunity may be reduced for new mutant strains, it is necessary to remain cautiously optimistic about the prospect of the pandemic under vaccination.