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Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

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Abstract

Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

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... Другой отличительной аминокислотной заменой, общей для субвариантов ВА.4 и ВА.5, является замена L452R, впервые выявленная у варианта «дельта». Данная замена также облегчает связывание с рецептором ACE2 10 . ...
... //www.sciencesetavenir.fr/sante/variant-ba-5-apres-le-portugal-les-autres-pays-europeens-vont-connaitre-leursixieme-vague_16368610 Rambaut A., Loman N., Pybus O., et al. ...
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Morbidity surveys in certain regions during the COVID-19 pandemic have established that the infection spreads in a wave-like manner characterised with peaks and troughs in incidence. According to the analysis of COVID-19 epidemic development in Russia, surges in COVID-19 infections are mainly driven by seasonal factors, insufficient herd immunity, and emerging SARS-CoV-2 variants with increased transmissibility. The aim of the study was to analyse environmental, biological and social factors contributing to new rises in COVID-19 cases in Russia. The study covers the global epidemiological situation as of mid-2022 and the role of environmental, biological, and social factors in the spread of COVID-19 in the Russian Federation. The results suggest that new highly contagious SARS-CoV-2 variants and seasonality are the principal factors driving new rises in morbidity. The authors assume that the sixth and the seventh COVID-19 waves in Russia will be in line with the best case scenario, which predicts the spread of a SARS-CoV-2 variant with increased transmissibility and reduced virulence.
... 80 An increase in threats of progression or development of symptomatic disease were also observed, even after complete dose of BNT162b2. 81 P681R mutation, may be crucial in causing the severe diseases by Delta variant. Based on an in vitro study involving B.1.617.2-infected ...
... 94 Ad26.COV2.S which implements the application of non-replicating viral vectors for the vaccination was also proven to be effective against some of the SARS-CoV-2 variants (Table 4). 95 Gazit et al. 81 suggested that complete vaccinations with BNT162b2 were exposed to a higher risk of breakthrough infections by B. (Table 5). 97 On the other hand, 2.61% out of 1, 497 vaccinated healthcare workers at Sheba Medical Centre, Israel, were confirmed with vaccine breakthrough infection, in which a huge proportion of the cases were female (64%) at an average age of 42 years old. ...
Article
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Since the first detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus remains a public health concern. Several public health measures have been implemented in an effort to curb the infections. However, the effectiveness of these strategies was threatened with the emergence of numerous SARS-CoV-2 variants in all parts of the globe, due to the persistent mutations as part of the viral evolution. Mutations that usually occur in its spike glycoprotein, allow SARS-CoV-2 to possess advantageous characteristics for its survivability and persistence. This has led to poor performance of diagnostic kits which have caused non-specific and insensitive detection of these variants, resulting in undetermined infection. The variants also have caused the increased severity of COVID-19, involving hospitalisation rates, ICU admissions, and deaths. Many have reported the vaccine-breakthrough infections and reduced effectiveness of vaccination, which is supposed to provide an effective degree of protection against COVID-19 infections. Due to these issues, this review summarises the impacts related to SARS-CoV-2 variants emergence towards the performance of diagnostic kits, transmissibility of the virus, severity of disease, and effectiveness of COVID-19 vaccines.
... This analysis led the authors to conclude that natural immunity in the convalescent subjects was superior in terms of protection than vaccination in the naïve individuals. Similar results have been reported in a retrospective observational study, where SARS-CoV-2-naïve vaccinees displayed higher risk for breakthrough infection than the previously infected individuals [6]. It is therefore quite reasonable to conclude that natural immunity may offer equal or greater protection against SARS-CoV-2 infection compared to vaccination [7]. ...
... Careful analysis of memory B-cell immunity elicited by natural infection and/or various vaccination/boosting regimens is an area of active ongoing research [4][5][6][7]. This is particularly important for lower-income countries and places where SARS-CoV-2 vaccination is no longer mandatory, properly controlled, or available, as immunity induced by the natural exposure to SARS-CoV-2 will likely remain the only factor limiting the spread of infection in such areas of the world. ...
Article
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Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions.
... 11 Emerging evidence suggests that vaccination with ChAdOx1 nCoV-19 (AstraZeneca), Ad26.COV2.S (Janssen), BNT162b2 (tozinameran; Pfizer-BioNtech), or mRNA-1273 (elasomeran; Moderna) confers additional protection against symptomatic reinfection among individuals with previous SARS-CoV-2 infection. [12][13][14][15][16][17][18] However, only one study has assessed protection against severe outcomes in previously infected individuals, with just 75 hospital admissions and two deaths. 18 Moreover, data for inactivated vaccines, which account for almost half of all doses given globally, are still needed. ...
... 33 The results of this analysis are consistent with studies reporting that individuals with previous SARS-CoV-2 infection who received ChAdOx1 nCoV-19 and BNT162b2 had a lower risk of symptomatic COVID-19 than those who were previously infected and unvaccinated. 12,13,15,16 Direct comparison with vaccine effectiveness estimates from these studies is challenged by differences in design, with most studies reporting risk in comparison with individuals who were unvaccinated and without a previous SARS-CoV-2 infection. However, inferred protection from those studies ranged from 40% to 94%, consistent with the magnitude of protection against symptomatic infection found for ChAdOx1 nCoV-19 (56·0%) and BNT162b2 (64·8%) in this study. ...
Article
Background COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. Methods Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. Findings Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1–42·6) for CoronaVac, 56·0% (51·4–60·2) for ChAdOx1 nCoV-19, 44·0% (31·5–54·2) for Ad26.COV2.S, and 64·8% (54·9–72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3–85·8) for CoronaVac, 89·9% (83·5–93·8) for ChAdOx1 nCoV-19, 57·7% (−2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3–97·7) for BNT162b2. Interpretation All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. Funding Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.
... We also need to recognize and duly consider the natural immunity acquired following a SARS-CoV-2 infection when establishing public health policies (Koch, 1939;Panda & Ding, 2015;Aung et al., 2016;Gazit et al., 2021;Pugh et al., 2022). There is mounting evidence that repeated https://doi.org/10.56098/ijvtpr.v3i1.65 COVID-19 injections may actually reduce the effectiveness of natural immunity against SARS-CoV-2 (Goldman et al., 2021;Bardosh et al., 2022;Guetzkow, 2022;Kampf, 2022). ...
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Case reports involving two academic researchers suggest that adverse events (AEs) to COVID-19 messenger RNA (mRNA) vaccination are largely underreported due to numerous clinical, systemic, political and media factors. The lack of proper analysis and consideration of the reported AEs also suggests that these injections are not as safe as widely purported. The resulting biased risk-benefit assessment may only produce misinformed public health recommendations and misguided political decisions, thereby exposing the population to an underestimated risk, in possible violation of the precautionary principle and of the right to a free and informed consent. The possible mechanisms underlying AEs to COVID-19 vaccination raise serious concerns regarding the new vaccine application of the mRNA technology that need to be addressed before expanding it to other infectious diseases. The legal considerations of AE underreporting are also discussed, and recommendations are formulated. AEs to mRNA injections are a reality and need to be better assessed than heretofore, diagnosed and reported to public health authorities for follow-up investigation in order to inform policy decisions and updates to physician guidelines in an objective, scientifically based, independent, and transparent manner.
... In line with other studies, we found that, in the predelta period, vaccine-induced and infection-induced protection were comparable for both mRNA vaccines, and vaccination following infection provided incremental protection against COVID-19 [41][42][43]. In the delta period, however, a history of infection was found to be more protective against re-infections compared to vaccination without prior infection, similar to evidence found in Israel and India [44,45], but in contrast to evidence from the US [46]. In our study, the relatively short average time since previous infection (4 months) could be the reason for higher protection among those with prior infection [43,47]. ...
Article
Background: It is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups. Methods: We conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time. Results: VE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12-15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex and race/ethnicity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the 2-dose mRNA-1273 vaccine (82% [95% CI: 80%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after 1-dose of the Ad26.COV2.S vaccine was the lowest compared to other vaccines (19% [95% CI: 15%, 23%]) in the delta period. Conclusions: VE against infection after two doses of the mRNA vaccines was high initially, but significantly reduced against the delta variant for both FDA-approved vaccines.
... However, as shown in Table 3, the best fit to the Aug. 2021 peak cases observed in Florida in our simulations is provided by the model characterized by a moderately-long (2.5 years) duration of immunity, indirectly supporting the above findings from empirical studies that the overall population-level immunity (from both vaccinations and natural infections) generated to SARS-CoV-2 is likely to wane but at a rate that may not cause too rapid a decline in the achieved immunity. There is also growing evidence, in this connection, that the effectiveness (and duration) of immunity from vaccinations may differ from that induced by natural infections [51]. Such differences, if true, could indeed be driving the present post-vaccination resurgence in cases observed for US states that have achieved the highest vaccination rates relative to those that are yet to attain such levels, such as Vermont (https://www.nytimes.com/interactive/2021/us/vermont-covid-cases.html). ...
Article
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The advent and distribution of vaccines against SARS-CoV-2 in late 2020 was thought to represent an effective means to control the ongoing COVID-19 pandemic. This optimistic expectation was dashed by the omicron waves that emerged over the winter of 2021/2020 even in countries that had managed to vaccinate a large fraction of their populations, raising questions about whether it is possible to use scientific knowledge along with predictive models to anticipate changes and design management measures for the pandemic. Here, we used an extended SEIR model for SARS-CoV-2 transmission sequentially calibrated to data on cases and interventions implemented in Florida until Sept. 24 th 2021, and coupled to scenarios of plausible changes in key drivers of viral transmission, to evaluate the capacity of such a tool for exploring the future of the pandemic in the state. We show that while the introduction of vaccinations could have led to the permanent, albeit drawn-out, ending of the pandemic if immunity acts over the long-term, additional futures marked by complicated repeat waves of infection become possible if this immunity wanes over time. We demonstrate that the most recent omicron wave could have been predicted by this hybrid system, but only if timely information on the timing of variant emergence and its epidemiological features were made available. Simulations for the introduction of a new variant exhibiting higher transmissibility than omicron indicated that while this will result in repeat waves, forecasted peaks are unlikely to reach that observed for the omicron wave owing to levels of immunity established over time in the population. These results highlight that while limitations of models calibrated to past data for precisely forecasting the futures of epidemics must be recognized, insightful predictions of pandemic futures are still possible if uncertainties about changes in key drivers are captured appropriately through plausible scenarios.
... Nuestro estudio evaluó la respuesta a ELISA desarrollado con antígeno de la variante Lambda, que fue la predominante durante la segunda ola. Se encontró presencia de reactividad, aunque en personas inmunizadas tuvo un IR más bajo de aquellos producidos con el virus original (B) (21) . Las variantes de la COVID-19 están reportando cada vez más mutaciones y cambios en su estructura con respecto al virus salvaje de Wuhan (22) , pues las variantes Delta y Ómicron presentan más mutaciones solo en la proteína espiga, ello explica en gran parte la evasión de la inmunidad previa obtenida por vacunas o infección previa (23) . ...
Article
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Objetivos. Evaluar la respuesta de preparados IgG por ELISA utilizando rígidos Wuhan y Lambda en trabajadores de la salud con y sin antecedentes de infección por SARS-CoV-2 antes de la inmunización con la primera y segunda dosis de la vacuna Sinopharm (BBIBP-CorV). Materiales y métodos.Se realizó un estudio analítico en trabajadores sanitarios mayores de 18 años. Se incluyeron 51 participantes con antecedentes y 100 participantes sin antecedentes de infección por SARS-CoV-2, que recibieron dos dosis de la vacuna Sinopharm. Los obtenidos IgG se evaluaron 21 días después de la primera dosis, 21 días después de la segunda dosis y 3 meses después de la segunda dosis mediante ELISA interno utilizando el endurecimiento completo de la variante de Wuhan (B.1.1) y la variante lambda ( C-37) del virus SARS-CoV-2. Resultados.Ambos grupos mostraron un gran aumento en el porcentaje de personas con resultados después de la segunda dosis, sin embargo, este porcentaje llegó a los 3 meses después de la segunda dosis. La diferencia entre el índice de estudios medidos por ELISA con variante de Wuhan versus ELISA con variante lambda fue significativa (p<0.001). Conclusiones. Hay un aumento significativo en la presencia de estudios tipo IgG después de 15 días de la segunda dosis de vacunación BBIBP-CorV en participantes sin infección previa y una disminución después de 3 meses de la segunda dosis en la proporción de índices de reactividad de estudios IgG en ELISA con la variante de diagnóstico como con ELISA con la variante lambda.
... Israel Gazit et al. (2021) reported on a study of 2.5 million people in Israel where the state has enacted, arguably, the world's most enforced COVID-19 mandates for lockdowns and injections. They found that SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. ...
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Are the promoters of the COVID-19 injections leading, pushing, and even forcing the people of the world to play a global game of Russian Roulette? The actuarial statistics and clinical facts are revealing harmful and deadly consequences on a global scale. For the sake of those still able to choose whether to spin the cylinder and pull the trigger one more time, I am conducting a guided tour. I will show why there are exponentially many more ways for the experimental injections to cause disease and death than health and well-being. Briefly put, valid transcription of mRNA from our own DNA leads to well-formed proteins that work as designed for cytoplasm, organelles, cells, tissues, and functional organ systems of the body. By contrast, the foreign (xeno) nucleic acid sequences, the mXNAs, in the “modified mRNA” in the COVID-19 injectables are more likely to harm the body’s systems than to benefit them. The relevant research shows why the mXNAs are incompetent to communicate effectively with the complex native context in vivo — the human biosignaling systems that are not mechanical but are articulated in multiple layers, interconnected, and for practical purposes, infinitely varied systems of information processing. Survival and longevity depend on valid communications among nuclear and mitochondrial DNA, their RNAs, and the protein language systems specified before a person’s birth. When these complex biosignaling systems fail, disorders and diseases follow. In catastrophic failures, death occurs. The story is not simple and the tour I am conducting is challenging with more than a few twists, turns, and digressions. However, I believe, persons experimented on — almost all of them unknowingly, some with partial knowledge who were unwilling recipients — account for more than half the world population. The stakes are high, even life or death, so I think many of the recipients of one or more injections will take the guided tour.
... Similarly, a study done by Callegaro et al. 17 in Italy reported that vaccines elicits a very strong immune response in seropositive individuals with antibody titer almost 10 fold higher to those without past SARS-CoV-2 infection. A retrospective observational study in Israel was done by Gazit et al. 18 which mentioned that natural immunity provided stronger and longer lasting protection against infection, symptomatic disease and hospitalization caused by Delta variant of SARS-CoV-2 19 . Suggested that the presence of anti-spike or antinucleocapsid IgG were associated with the less chance of SARS-CoV-2 re-infection in the next 6 months. ...
Article
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Introduction: A novel coronavirus (2019-nCoV or SARS-CoV-2) emerged at the end of 2019 in Wuhan, Hubei province, China named as COVID-19. IgM, the first antibody produced by the body, is generated gradually 1 week after symptom onset and declines by 4 weeks after the COVID infection. In this background, the antibody response was observed in vaccinated (by Oxford-AstraZeneca) doctors of SSMC(Sir Salimullah Medical College) with or without previous COVID-19 infection. Methodology: This cross-sectional analytical study was conducted in the Department of Biochemistry and Molecular Biology at SSMC and BSMMU. A total of 70 doctors of SSMC aged 25-59 years were enrolled according to inclusion criteria. Among them 35 vaccinated doctors were previously infected by SARS-CoV-2 regarded as group A and another vaccinated 35 doctors were non-infected regarded as group B. Collected data was analyzed by Statistical Package for Social Science 26 (SPSS 26). The data were expressed as frequency and percentage, mean ± SD for normally distributed data or median (inter-quartile rage) for data not normally distributed. Mann-Whitney test was done to compare IgG status between vaccinated SARS-CoV-2 infected and non-infected individuals. Result: There was significantly higher level of antibodies (serum IgG level) present in fully vaccinated doctors with previous SARS-CoV-2 infection than in only vaccinated doctors without prior infection. Update Dent. Coll. j: 2022; 12(2): 19-23
... This should be further investigated, as the response has been described to be variable in vaccinated individuals and vaccines may not be equally effective against new SARS-CoV-2 variants [8]. The study published by Gazit S et al. showed that unvaccinated individuals had around a 13-fold increased risk to be infected with Delta variant than people with a past infection [33]. On the contrary, other studies have shown that vaccinated individuals had similar responses to convalescent ones, producing a cellular response at the same level as the humoral, even at an earlier stage. ...
Article
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The measurement of specific T-cell responses can be a useful tool for COVID-19 diagnostics and clinical management. In this study, we evaluated the IFN-γ T-cell response against the main SARS-CoV-2 antigens (spike, nucleocapsid and membrane) in acute and convalescent individuals classified according to severity, and in vaccinated and unvaccinated controls. IgG against spike and nucleocapsid were also measured. Spike antigen triggered the highest number of T-cell responses. Acute patients showed a low percentage of positive responses when compared to convalescent (71.6% vs. 91.7%, respectively), but increased during hospitalization and with severity. Some convalescent patients showed an IFN-γ T-cell response more than 200 days after diagnosis. Only half of the vaccinated individuals displayed an IFN-γ T-cell response after the second dose. IgG response was found in a higher percentage of individuals compared to IFN-γ T-cell responses, and moderate correlations between both responses were seen. However, in some acute COVID-19 patients specific T-cell response was detected, but not IgG production. We found that the chances of an IFN-γ T-cell response against SARS-CoV-2 is low during acute phase, but may increase over time, and that only half of the vaccinated individuals had an IFN-γ T-cell response after the second dose.
... This is comforting because neutralization titers decrease over time [28] and protective immunity acquired from past SARS-CoV-2 infection is not guaranteed due to the variable immune responses generated. However, another found that people who have protection from previous infection alone have a 13-fold reduced chance of re-infection than those who received both doses of the Pfizer-BioNTech (BNT162b2) mRNA vaccine [29]. ...
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BACKGROUND OF THE STUDY: The implementation of the vaccine on a large scale has almost reached all provinces in Indonesia. East Kalimantan, one of the provinces affected by COVID-19, has also implemented a vaccine program. Seroprevalence surveys are essential to describe the success of vaccine program based on antibody titre test. AIM OF THE STUDY: This study aims to determine the anti-SARS-CoV-2 antibody titre value based on the type of vaccine received by the academic community in Samarinda, one of the cities most affected by COVID-19 in East Kalimantan. METHODOLOGY: The study was population-based. The study sampled 100 people from the community. Participants must be in good health, aged 16-60, with a positive COVID-19 test, no comorbid illnesses or other chronic problems, no blood transfusions, and most importantly, have received the least initial dosage of immunization. The data will be analyzed using SPSS 26 and STATA 16. A normality test and Tobit regression test to determine the antibody distribution in each vaccine type. RESULTS: The results showed that Moderna COVID-19 Vaccine provided a significant (p=0.001) increase in antibody prediction of 1090 U/ml (95% CI: 764-1416), while Pfizer provided a significant (p=0.000) rise of 766 U/ml (95% CI: 307-1226). CONCLUSION: According to the results of a seroprevalence survey conducted among the academic community in East Kalimantan, receivers of inactivated vaccinations outnumbered those of mRNA and vector-based vaccines. It can be determined that booster immunizations for students and academic staff are required to guard against COVID-19 infection. As boosters, both Moderna's COVID-19 Vaccine and Pfizer's COVID-19 Vaccine are strongly recommended.
... Immune waning is assumed to occur with half-life times that depend on the immunity source. Vaccine-induced immunity is assumed to wane with half-life times equal to 6 months and 3 months for primary shots and boosters, respectively 13 . Hence, immunity derived from booster vaccination provides strong but short lived protection 14 . ...
... Another study showed the relative risk to be five times in the recovered compared to those who were vaccinated (Bozio et al., 2021). It had been suggested that there is a difference in the immune response in these two groups with infection-induced immunity producing a lower antibody level, but longer memory cells and vice versa for vaccination-induced immunity (Cho et al., 2021, Gazit et al., 2021. We observed no deaths amongst vaccinated reinfections, however this observed rate showed an upper 97.% Cl of 2.7 deaths per 1000. ...
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Objectives . SARS-CoV-2 vaccination has shown reduced infection severity; however, the reinfection frequency amongst unvaccinated, partially vaccinated and fully vaccinated remains unclear. This study aims to elucidate the rates and associated factors for such occurrences. Methods . This retrospective epidemiological report included 1362 COVID-19 reinfection cases in Bahrain between April 2020 and July 2021. We analysed differences in disease severity and reinfection characteristics between various vaccination statuses; fully vaccinated, interrupted vaccination, one vaccination dose, post-reinfection vaccination and unvaccinated. Results . Reinfection cases increased from zero cases per month in April – June 2020 to a sharp peak of 579 reinfection cases in May 2021. Males constituted a significantly larger proportion of reinfections (60.3%, p<0.0001). Reinfection episodes were highest amongst the 30-39 years of age (29.7%). The least reinfection episodes occurred at 3-6 months after the first infection (20.6%) and most occurred ≥9 months after initial infection (46.4%). Most individuals were asymptomatic during both episodes (35.7%), Reinfection disease severity was mild, with vaccinated patients less likely to have symptomatic reinfection (OR 0·71, p=0·004). Only 6.6% reinfection cases required hospitalization. One death was recorded, corresponding to unvaccinated group. Conclusion . Vaccine-induced immunity and prior infection with or without vaccination were effective in reducing reinfection disease severity.
... Several observational studies profiling millions of humans support that hybrid immunity (one or more doses of vaccines and infection) is superior to two or even three doses of vaccines in preventing severe infection/hospitalization with emerging variants [56][57][58] . The superiority of hybrid immunity has been documented when the primary infection was with the Delta VOC, and now, more recently, with the Omicron VOC [59][60][61][62] . Mechanistic studies have uncovered important observations about the quality/quantity of the immune responses that explain the superiority of hybrid immunity over vaccine-induced immunity: (1) potent antibody responses with increased coverage that can neutralize multiple variants 63,64 , (2) the ability to elicit superior Fc-dependent functions 65 , and (3) unique subsets of T cells with the secretion of IFNγ and IL10 66 . ...
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Immunization programs against SARS-CoV-2 with commercial intramuscular (IM) vaccines prevent disease but not infections. The continued evolution of variants of concern (VOC) like Delta and Omicron has increased infections even in countries with high vaccination coverage. This is due to commercial vaccines being unable to prevent viral infection in the upper airways and exclusively targeting the spike (S) protein that is subject to continuous evolution facilitating immune escape. Here we report a multi-antigen, intranasal vaccine, NanoSTING-NS that yields sterilizing immunity and leads to the rapid and complete elimination of viral loads in both the lungs and the nostrils upon viral challenge with SARS-CoV-2 VOC. We formulated vaccines with the S and nucleocapsid (N) proteins individually to demonstrate that immune responses against S are sufficient to prevent disease whereas combination immune responses against both proteins prevents viral replication in the nasal compartment. Studies with the highly infectious Omicron VOC showed that even in vaccine-naïve animals, a single dose of NanoSTING-NS significantly reduced transmission. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to preventing transmission and ending the pandemic, and (2) an explanation for why hybrid immunity in humans is superior to vaccine-mediated immunity by current IM vaccines.
... Thus, only 11.4% of the Kyrgyz population is protected from COVID-19 to some extent [6]. A certain contribution to protection is also made by post-infectious immunity that develops as a result of transmitted COVID-19 [9][10][11]. Thus, the real seroprevalence level of the population consists of postinfectious and post-vaccination components of seropositivity. ...
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In the fight against coronavirus infection, control of the immune response is of decisive importance, an important component of which is the seroprevalence of antibodies to SARS-CoV-2. Immunity to SARS-CoV-2 is formed either naturally or artificially through vaccination. The purpose of this study was to assess the seroprevalence of antibodies to SARS-CoV-2 in the population of Kyrgyzstan. A cross-sectional randomized study of seroprevalence was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the Association of Preventive Medicine (Kyrgyzstan) and the St. Petersburg Pasteur Institute (Russia) approved the study. Volunteers (9471) were recruited, representing 0.15% (95% CI 0.14–0.15) of the total population, randomized by age and region. Plasma antibodies (Abs) to the nucleocapsid antigen (Nag) were determined. In vaccinated individuals, Abs to the SARS-CoV-2 receptor-binding domain antigen (RBDag) were determined. Differences were considered statistically significant at p < 0.05. The SARS-CoV-2 Nag Ab seroprevalence was 48.7% (95% CI 47.7–49.7), with a maximum in the 60–69 age group [59.2% (95% CI 56.6–61.7)] and a minimum in group 1–17 years old [32.7% (95 CI: 29.4–36.1)]. The highest proportion of seropositive individuals was in the Naryn region [53.3% (95% CI 49.8–56.8)]. The lowest share was in Osh City [38.1% (95% CI 32.6–43.9)]. The maximum SARS-CoV-2 Nag seropositivity was found in the health-care sector [57.1% (95% CI 55.4–58.8)]; the minimum was seen among artists [38.6% (95% CI 26.0–52.4)]. Asymptomatic SARS-CoV-2 Nag seropositivity was 77.1% (95% CI 75.6–78.5). Vaccination with Sputnik V or Sinopharm produced comparable Ab seroprevalence. SARS-CoV-2 Nag seropositivity in the Kyrgyz population was 48.75% (95% CI 47.7–49.7), with the mass vaccination campaign undoubtedly benefitting the overall situation.
... Studies have established that natural immunity is 13 to 26 times more robust than vaccine-induced immunity. [11] Another resource-intensive, costly, and futile activity during the pandemic was the emphasis on testing, contact tracing, and isolation throughout the course of the pandemic. These measures are important in the early phase of the pandemic before community transmission has set in, after which they are futile. ...
... Initial studies reported that previously infected patients had the highest antibody titers and neutralizing activity against the S protein [46,47] by boosting the quantity, quality, and breadth of the humoral response [48]. Moreover, natural infection was associated with longer and stronger protection against reinfections and hospitalization [49], this hypothesis was later supported by Dhumal et al. [50] and Abu-Raddad et al. [51], in which a low probability of reinfection during the second waves of infection after vaccine application and natural infection was reported. This information could be a guiding factor in the design of more effective vaccination schemes for the future. ...
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The BNT162b2 Pfizer/BioNTech vaccine was the first emergency approved vaccine during the COVID-19 pandemic. The aim of this systematic review was to examine the variations in the humoral immune response induced by the administration of the BNT162b2 vaccine in patients with previous SARS-CoV-2 infection, the elderly, and those with comorbidities and immunosuppression states. Additionally, we analyzed the effect of generated neutralizing antibodies against the new variants of concern of SARS-CoV-2. Pubmed, Science Direct, Mendeley, and WorldWide Science were searched between 1 January 2020 and October 2021 using the keywords “BNT162b2”, “serology”, “comorbidity”, “immunosuppression”, and “variants of concern”dA total of 20 peer-reviewed publications were selected. The analysis showed that those individuals with previous infections have a considerably higher antibody response after the administration of BNT162b2 vaccine in contrast with seronegative individuals. With regard to variation in immune responses, elderly individuals, patients with cancer, or patients who had undergone a kidney transplant, dialysis, or who were pregnant had a lower antibody response in comparison to healthy individuals. Finally, antibodies developed against the S protein produced by the BNT162b2 vaccine, possessed lower neutralizing activity against the alpha, beta, gamma, and delta variants of SARS-CoV-2. In conclusion, patients with immunodeficiencies and comorbidities have a lesser antibody response, about which further studies need to be performed in order to analyze the effectiveness and duration of the humoral immunity associated with vaccination in these specific populations.
... Children very rarely develop serious or long COVID-19 and might be better off acquiring immunity by natural infections. The value of repeated vaccination is also questionable for healthy young and middle-aged adults, especially as natural infections induce stronger and more sustained protection against further infections than mRNA vaccines (7). Vaccines are, however, vital for the elderly and vulnerable, as brutally illustrated by the much higher recent death rate in Hong Kong (with low vaccination rates of care home residents) than South Korea (with its elderly extensively vaccinated). ...
... We found that the response to vaccination is different among subjects vaccinated after infection or when naïve: while a marked increase in S-targeting antibodies is observed in all individuals, antibodies induced by vaccination are higher in previously infected subjects. In vaccinated previously infected subjects, a single dose of vaccine is shown to boost a strong neutralisation response, as confirmed in other studies [18,41]. This suggests that a single dose of vaccine in previously infected individuals induces a robust immune response in support of the vaccination strategy implemented in Germany, France, Italy, and Israel among other countries. ...
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Background: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. Methods: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). Results: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. Conclusions: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population.
... While some studies report rapid decline in SARS-CoV-2 specific neutralizing IgM and IgG levels (Xiang et al., 2021), other studies reported the long-lasting immunological memory against SARS-CoV-2 (Jung et al., 2021;Keeton et al., 2022;Tarke et al., 2022). Previous studies also suggested that natural infection induces a broader spectrum of protection against multiple variants (Dan et al., 2021;Gazit et al., 2021). In South Korea and Singapore, both of which had successful quarantines, the highly transmissible Delta variant spread during low-level quarantines despite high vaccination rates. ...
Article
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South Korea adopted stringent preventive measures against Coronavirus virus disease 2019, resulting in three small and one large outbreaks until January 15, 2022. The fatality rate was 2.5-fold higher during peak transmission periods than in base periods. As new variants of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are continuously emerging, the need for understanding their epidemic potential remains necessary. In South Korea, the epidemiologic data obtained from mass diagnostic testing enabled investigation of the true number of infected cases, exact incidence, and fatality numbers. Analysis found a similarity between estimated infection rates and confirmed cases. This suggested that the number of confirmed cases had an influence on the fatality rate as a quantitative parameter. The fatality rate decreased even as infection with SARS-CoV-2 variants rose. In comparative analysis, the confirmed cases in young people (ages 20–29) increased prior to every outbreak peak and marked the tipping point in infection spread. These results indicate that a high level of SARS-CoV-2 infection in young population drives peak incidence and mortality across all age groups.
... Although adverse effects after the booster dose are generally considered rare [28], they should not be taken lightly and unnecessary vaccination of individuals with already highly stimulated immunity is not likely to improve their immunity against SARS-CoV-2. For this reason, the matter of individual approach to the booster dose in such individuals should be further discussed [29][30][31]. ...
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Background and aims: Elderly nursing home residents are especially prone to a severe course of SARS-CoV-2 infection. In this study, we aimed to investigate the complex immune response after vaccination depending on the convalescence status and vaccine. Methods: Sampling took place in September-October 2021. IgG antibodies against spike protein and nucleocapsid protein, the titer of virus neutralization antibodies against delta and (on a subset of patients) omicron, and cellular immunity (interferon-gamma release assay) were tested in nursing home residents vaccinated with Pfizer, Moderna (both 30-31 weeks after the completion of vaccination), or AstraZeneca (23 weeks) vaccines. The prevalence with 95% confidence intervals (CI) was evaluated in Stata version 17. Results: 95.2% (95% CI: 92.5-97.1%) of the 375 participants had positive results of anti-S IgG, 92.8% (95% CI: 89.7-95.2%) were positive in virus neutralization assay against delta, and 89.0% (95% CI: 84.5-92.5%) in the interferon-gamma-releasing assay detecting cellular immunity. Results of the virus neutralization assay against omicron correlated with those against delta but the neutralization capacity was reduced by about half. As expected, the worst results were found for the AstraZeneca vaccine, although the vaccination-to-test period was the shortest for this vaccine. All immune parameters were significantly higher in convalescent residents than in naive residents after vaccination. No case of COVID-19 occurred during the vaccination-to-test period. Conclusions: A high immune response, especially among vaccinated convalescents (i.e., residents with hybrid immunity), was found in elderly nursing home residents 5-7 months after vaccination against SARS-CoV-2. In view of this, it appears that such residents are much better protected from COVID-19 than those who are only vaccinated and the matter of individual approach to the booster dose in such individuals should be further discussed.
... A significant benefit of determining cellular response specificity is also winning the race against emerging notorious strains such as B. (116)(117)(118)(119)(120). Kojima and Klausner reviewed published biological studies (including the recent period of predominantly delta variant spread) and found significant results, which documented that previous infection provides remarkable immunity with a shallow reinfection incidence rate and hospitalization frequency (121). An Israeli population epidemiological analysis has concluded that SARS-CoV-2-naïve vaccinated people had a 13.06 times increased risk of breakthrough infection (an infection that occurs in fully vaccinated people) with the B.1.617.2 variant compared to those who were COVID-19 convalescents (122). Moreover, Primorac et al. found that out of 200 study participants, only 1 individual who recovered from COVID-19 (0.5%) was reinfected, while 6 participants (3%) were affected by breakthrough SARS-CoV-2 infection after receiving the vaccine (67). ...
Article
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Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and translate it to the population of the whole world in record time. Following the infection with the viral antigen, adaptive immune responses are activated mainly by viral particle encounters with the antigen-presenting cells or B cell receptors, which induce further biological interactions to defend the host against the virus. After the infection has been warded off, the immunological memory is developed. The SARS-CoV cellular immunity has been shown to persist even 17 years after the infection, despite the undetectable humoral component. Similar has been demonstrated for the SARS-CoV-2 T cell memory in a shorter period by assessing interferon-gamma levels when heparinized blood is stimulated with the virus-specific peptides. T cells also play an irreplaceable part in a humoral immune reaction as the backbone of a cellular immune response. They both provide the signals for B cell activation and the maturation, competence, and memory of the humoral response. B cell production of IgA was shown to be of significant influence in mediating mucosal immunity as the first part of the defense mechanism and in the development of nasal vaccines. Here, we interpret the recent SARS-CoV-2 available research, which encompasses the significance and the current understanding of adaptive immune activity, and compare it among naive, exposed, and vaccinated blood donors. Our recent data showed that those who recovered from COVID-19 and those who are vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Additionally, we analyze the humoral responses in immunocompromised patients and memory mediated by cellular immunity and the impact of clonality in the SARS-CoV-2 pandemic regarding breakthrough infections and variants of concern, both B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.
... 22 Other studies have shown that natural immunity due to previous infection might be more effective against the new variants than vaccine-induced immunity, but that such protection can be enhanced by additional vaccination. [23][24][25][26] Our data, which show that natural immunity due to previous exposure to SARS-CoV-2 provided 83·2% protection against any COVID-19 reinfection, provides further support for these observations. Moreover this immunity was sufficient to prevent any severe cases of COVID-19, especially COVID-19-associatedhospitalisations, which will be important for national health resources to have the capacity to deal with future waves of infection. ...
Article
Background We previously reported the efficacy of the adjuvanted-protein COVID-19 vaccine candidate S-Trimer (SCB-2019) in adults who showed no evidence of previous exposure to SARS-CoV-2. In this study, we aimed to investigate the extent of protection afforded by previous exposure to SARS-CoV-2 on subsequent COVID-19 infection, as well as the efficacy, safety, and reactogenicity of SCB-2019 in participants who were enrolled in the Study evaluating Protective-Efficacy and safety of Clover's Trimeric Recombinant protein-based and Adjuvanted COVID-19 vaccine (SPECTRA) trial who had already been exposed to SARS-CoV-2 before vaccination. Methods In a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial (SPECTRA) done at 31 sites in five countries, participants were randomly assigned 1:1 using the Cenduit Interactive Response Technology system (IQVIA, Durham, NC, USA), with a block size of six, to receive two doses of either SCB-2019 or placebo 21 days apart. The primary outcomes of the SPECTRA trial were vaccine efficacy, measured by real-time PCR (rtPCR)-confirmed COVID-19 of any severity, with onset from 14 days after the second vaccine dose, as well as the safety and solicited local and systemic adverse events in the phase 2 subset. Here, we present secondary analyses to calculate the protective efficacy due to previous exposure to SARS-CoV-2 against reinfection with COVID-19 according to severity in SPECTRA participants who had evidence of exposure to SARS-CoV-2 at baseline, including efficacy against identified viral variants, as well as efficacy of SCB-2019 vaccination in this population. Findings We enrolled 30 174 participants between March 24, 2021, and Aug 10, 2021. In the 14 670 participants who were randomly assigned to receive placebo, there were 418 (2·8%) confirmed cases of COVID-19; 65 (0·9%) of 7339 SARS-CoV-2-exposed participants, and 353 (4·8%) of 7331 SARS-CoV-2-naive participants (attack rates of 5·5 cases per 100 person-years for SARS-CoV-2-exposed participants and 32·4 cases per 100 person-years for SARS-CoV-2-naive participants). Protective efficacy due to previous exposure to SARS-CoV-2 was 83·2% (95% CI 78·0–87·3) against any COVID-19, 92·5% (82·9–97·3) against moderate-to-severe COVID-19, and 100% (59·3–100) against severe COVID-19; no SARS-CoV-2-exposed participants had hospitalisation associated with COVID-19. Protective efficacy against variants were 100% for alpha (B.1.1.7) and lambda (C.37) variants, 88·6% (14·9–99·7) for B.1.623, 93·6% (80·1–98·7) for gamma (P.1), and 92·4% (81·2–97·6) for mu (B.1.621) variants, and lowest against beta (B.1.351; 72·2% [33·1–89·9]) and delta (B.1.617.2; 77·2% [61·3–87·2]) variants. In addition, one dose of SCB-2019 had 49·9% (1·5–75·6) efficacy against any symptomatic COVID-19, and two doses had 64·2% (26·5–83·8) efficacy. SCB-2019 was well tolerated in SARS-CoV-2-exposed participants, but was associated with higher rates of injection site pain (89 [33·8%] of 263 participants) than placebo (16 [6·7%] of 239 participants). Rates of solicited systemic adverse events, severe adverse events, and serious adverse events were similar between vaccine and placebo groups, and with rates in SARS-CoV-2-naive vaccine recipients. Interpretation Previous exposure to SARS-CoV-2 decreased the risk and severity of subsequent COVID-19 infection, even against newly emerging variants. Protection is further enhanced by one or two doses of SCB-2019. Funding Clover Biopharmaceuticals, The Coalition for Epidemic Preparedness Innovations (CEPI).
... Surprisingly, our outreach campaign revealed that many HCWs refused the vaccine due to their prior exposure, believing erroneously that prior exposure is just as effective at eliciting a humoral immune response as vaccination. Our data indicates that even in participants previously exposed to SARS-CoV-2, mRNA vaccination induces a significant increase in humoral immunity, and vaccination produces higher levels of SARS-CoV-2 antibodies compared to prior exposure, corroborating other studies that have found previously infected but unvaccinated individuals to be at a higher risk for contracting severe disease compared to vaccinated individuals (27,28). We hypothesized that different subgroups of HCWs would have varying SARS-CoV-2 antibody levels following vaccination, with older individuals having decreasing antibody levels at later time points as observed in prior studies (10,29,30). ...
Article
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Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2.
... There is evidence of waning naturally derived immunity, suggesting that an individual might become more broadly susceptible to reinfection sometime after exposure. 70 This empirical analysis of past COVID-19 infections ends at the point where the omicron (B.1.1.529) wave was first detected in Gauteng province in South Africa. ...
Article
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Background Timely, accurate, and comprehensive estimates of SARS-CoV-2 daily infection rates, cumulative infections, the proportion of the population that has been infected at least once, and the effective reproductive number (Reffective) are essential for understanding the determinants of past infection, current transmission patterns, and a population's susceptibility to future infection with the same variant. Although several studies have estimated cumulative SARS-CoV-2 infections in select locations at specific points in time, all of these analyses have relied on biased data inputs that were not adequately corrected for. In this study, we aimed to provide a novel approach to estimating past SARS-CoV-2 daily infections, cumulative infections, and the proportion of the population infected, for 190 countries and territories from the start of the pandemic to Nov 14, 2021. This approach combines data from reported cases, reported deaths, excess deaths attributable to COVID-19, hospitalisations, and seroprevalence surveys to produce more robust estimates that minimise constituent biases. Methods We produced a comprehensive set of global and location-specific estimates of daily and cumulative SARS-CoV-2 infections through Nov 14, 2021, using data largely from Johns Hopkins University (Baltimore, MD, USA) and national databases for reported cases, hospital admissions, and reported deaths, as well as seroprevalence surveys identified through previous reviews, SeroTracker, and governmental organisations. We corrected these data for known biases such as lags in reporting, accounted for under-reporting of deaths by use of a statistical model of the proportion of excess mortality attributable to SARS-CoV-2, and adjusted seroprevalence surveys for waning antibody sensitivity, vaccinations, and reinfection from SARS-CoV-2 escape variants. We then created an empirical database of infection–detection ratios (IDRs), infection–hospitalisation ratios (IHRs), and infection–fatality ratios (IFRs). To estimate a complete time series for each location, we developed statistical models to predict the IDR, IHR, and IFR by location and day, testing a set of predictors justified through published systematic reviews. Next, we combined three series of estimates of daily infections (cases divided by IDR, hospitalisations divided by IHR, and deaths divided by IFR), into a more robust estimate of daily infections. We then used daily infections to estimate cumulative infections and the cumulative proportion of the population with one or more infections, and we then calculated posterior estimates of cumulative IDR, IHR, and IFR using cumulative infections and the corrected data on reported cases, hospitalisations, and deaths. Finally, we converted daily infections into a historical time series of Reffective by location and day based on assumptions of duration from infection to infectiousness and time an individual spent being infectious. For each of these quantities, we estimated a distribution based on an ensemble framework that captured uncertainty in data sources, model design, and parameter assumptions. Findings Global daily SARS-CoV-2 infections fluctuated between 3 million and 17 million new infections per day between April, 2020, and October, 2021, peaking in mid-April, 2021, primarily as a result of surges in India. Between the start of the pandemic and Nov 14, 2021, there were an estimated 3·80 billion (95% uncertainty interval 3·44–4·08) total SARS-CoV-2 infections and reinfections combined, and an estimated 3·39 billion (3·08–3·63) individuals, or 43·9% (39·9–46·9) of the global population, had been infected one or more times. 1·34 billion (1·20–1·49) of these infections occurred in south Asia, the highest among the seven super-regions, although the sub-Saharan Africa super-region had the highest infection rate (79·3 per 100 population [69·0–86·4]). The high-income super-region had the fewest infections (239 million [226–252]), and southeast Asia, east Asia, and Oceania had the lowest infection rate (13·0 per 100 population [8·4–17·7]). The cumulative proportion of the population ever infected varied greatly between countries and territories, with rates higher than 70% in 40 countries and lower than 20% in 39 countries. There was no discernible relationship between Reffective and total immunity, and even at total immunity levels of 80%, we observed no indication of an abrupt drop in Reffective, indicating that there is not a clear herd immunity threshold observed in the data. Interpretation COVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation. Our statistical approach to estimating SARS-CoV-2 infection allows estimates to be updated and disseminated rapidly on the basis of newly available data, which has and will be crucially important for timely COVID-19 research, science, and policy responses. Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.
... 19 Additionally, the absolute risk reduction associated with hybrid immunity in the present study was small, indicating that to prevent one SARS-CoV-2 reinfection among those with natural immunity, 767 individuals would need to be vaccinated with two doses. Similar results were reported in an Israeli preprint study including 14 029 matched pairs, 31 in which one additional dose of vaccine in those with natural immunity was associated with seven fewer cases of symptomatic reinfection, suggesting that about 2000 individuals needed to be vaccinated to prevent one reinfection. If these associations are causal, the overall clinical relevance of these effects appears uncertain. ...
Article
Background Real-world evidence supporting vaccination against COVID-19 in individuals who have recovered from a previous SARS-CoV-2 infection is sparse. We aimed to investigate the long-term protection from a previous infection (natural immunity) and whether natural immunity plus vaccination (hybrid immunity) was associated with additional protection. Methods In this retrospective cohort study, we formed three cohorts using Swedish nationwide registers managed by the Public Health Agency of Sweden, the National Board of Health and Welfare, and Statistics Sweden. Cohort 1 included unvaccinated individuals with natural immunity matched pairwise on birth year and sex to unvaccinated individuals without natural immunity at baseline. Cohort 2 and cohort 3 included individuals vaccinated with one dose (one-dose hybrid immunity) or two doses (two-dose hybrid immunity) of a COVID-19 vaccine, respectively, after a previous infection, matched pairwise on birth year and sex to individuals with natural immunity at baseline. Outcomes of this study were documented SARS-CoV-2 infection from March 20, 2020, until Oct 4, 2021, and inpatient hospitalisation with COVID-19 as main diagnosis from March 30, 2020, until Sept 5, 2021. Findings Cohort 1 was comprised of 2 039 106 individuals, cohort 2 962 318 individuals, and cohort 2 and 3 567 810 individuals. During a mean follow-up of 164 days (SD 100), 34 090 individuals with natural immunity in cohort 1 were registered as having had a SARS-CoV-2 reinfection compared with 99 168 infections in non-immune individuals; the numbers of hospitalisations were 3195 and 1976, respectively. After the first 3 months, natural immunity was associated with a 95% lower risk of SARS-CoV-2 infection (adjusted hazard ratio [aHR] 0·05 [95% CI 0·05–0·05] p<0·001) and an 87% (0·13 [0·11–0·16]; p<0·001) lower risk of COVID-19 hospitalisation for up to 20 months of follow-up. During a mean follow-up of 52 days (SD 38) in cohort 2, 639 individuals with one-dose hybrid immunity were registered with a SARS-CoV-2 reinfection, compared with 1662 individuals with natural immunity (numbers of hospitalisations were eight and 113, respectively). One-dose hybrid immunity was associated with a 58% lower risk of SARS-CoV-2 reinfection (aHR 0·42 [95% CI 0·38–0·47]; p<0·001) than natural immunity up to the first 2 months, with evidence of attenuation thereafter up to 9 months (p<0·001) of follow-up. During a mean follow-up of 66 days (SD 53) in cohort 3, 438 individuals with two-dose hybrid immunity were registered as having had a SARS-CoV-2 reinfection, compared with 808 individuals with natural immunity (numbers of hospitalisations were six and 40, respectively). Two-dose hybrid immunity was associated with a 66% lower risk of SARS-CoV-2 reinfection (aHR 0·34 [95% CI 0·31–0·39]; p<0·001) than natural immunity, with no significant attenuation up to 9 months (p=0·07). To prevent one reinfection in the natural immunity cohort during follow-up, 767 individuals needed to be vaccinated with two doses. Both one-dose (HR adjusted for age and baseline date 0·06 [95% CI 0·03–0·12]; p<0·001) and two-dose (HR adjusted for age and baseline date 0·10 [0·04–0·22]; p<0·001) hybrid immunity were associated with a lower risk of COVID-19 hospitalisation than natural immunity. Interpretation The risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals who have survived and recovered from a previous infection remained low for up to 20 months. Vaccination seemed to further decrease the risk of both outcomes for up to 9 months, although the differences in absolute numbers, especially in hospitalisations, were small. These findings suggest that if passports are used for societal restrictions, they should acknowledge either a previous infection or vaccination as proof of immunity, as opposed to vaccination only. Funding None.
... One particular study discovered that people who received the BioNTech-Pfizer vaccination but had never tested positive for COVID were 13 times more likely to contract the Delta form than those who had been infected but had not been vaccinated. Despite the fact that it has not yet been peer reviewed, that study is now the largest comparison of immunity gained from previous COVID-19 infection to vaccine-induced immunity, with over 30,000 patients having participated in the survey [86]. ...
Article
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The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with no signs of abatement in sight. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of this pandemic and has claimed over 5 million lives, is still mutating, resulting in numerous variants. One of the newest variants is Omicron, which shows an increase in its transmissibility, but also reportedly reduces hospitalization rates and shows milder symptoms, such as in those who have been vaccinated. As a result, many believe that Omicron provides a natural vaccination, which is the first step toward ending the COVID-19 pandemic. Based on published research and scientific evidence, we review and discuss how the end of this pandemic is predicted to occur as a result of Omicron variants being surpassed in the community. In light of the findings of our research, we believe that it is most likely true that the Omicron variant is a natural way of vaccinating the masses and slowing the spread of this deadly pandemic. While the mutation that causes the Omicron variant is encouraging, subsequent mutations do not guarantee that the disease it causes will be less severe. As the virus continues to evolve, humans must constantly adapt by increasing their immunity through vaccination.
... Foremost, the scientific evidence must be considered. Specific to SARS-CoV-2, some results suggest that vaccine-induced immunity is more effective, 3 other results suggest that natural immunity is more effective, 4 and some findings estimate both options as roughly equal. 5 All evidence appears to support that prior immunity helps reduce frequency of severe outcomes and prevents future infections. ...
... A c c e p t e d M a n u s c r i p t However, increasing data indicate that immunity declines over time after both natural infection [1] and vaccination [2]. In a recently published study, natural immunity was shown to confer longer-lasting and stronger protection against infection and symptomatic disease than immunity induced by two doses of the BioNTech/Pfizer mRNA BNT162b2 vaccine [3]. ...
Article
We compared the ability of SARS-CoV2 Spike-specific antibodies to induce natural killer (NK) cell-mediated antibody dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 COVID-19 patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than three months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination.
... Der Vergleich zu Geimpften fällt ebenfalls günstiger aus: Personen nach einer Zweifachimpfung hatten im Vergleich zu denen, die eine Infektion überstanden hatten, ein um den Faktor 13,6 erhöhtes Risiko, eine Durchbruchsinfektion zu erleiden -in dem untersuchten Fall war es wieder die Delta-Variante. Geimpften drohte bei einer Infektion überdies eher eine Hospitalisierung als Genesenen (12). ...
Article
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Vaccination effects to protect against COVID-19 vanish the sooner, the more often people are boostered - a well known effect from influenca vaccination strategies. On the contrary - infection offers a longer lasting protection effect, which can be shown for COVID-19 infections too. Here is summerized, that the immune reactions following COVID-19 could be - as many experts argue now - a valuable tool to gain stable herd immunity. So those recovered from COVID-19 might be a very important group in societies to install broad immunity on the long run.
... The IAR was relatively high and vaccination rates were relatively low comparing to other developed countries [21]. Gazit et al. [44] concluded that compared with two doses of BNT162b2 vaccine induced immunity, infection induced immunity had a longer duration and stronger protective effect on symptomatic diseases caused by delta variant. Although it was not a study of the P.1 variant, one would expect similar effects. ...
Article
Backgrounds Brazil has suffered two waves of Coronavirus Disease 2019 (COVID-19). The second wave, coinciding with the spread of the Gamma variant, was more severe than the first wave. Studies have not yet reached a conclusion on some issues including the extent of reinfection, the infection fatality rate (IFR), the infection attack rate (IAR) and the effects of the vaccination campaign in Brazil, though it was reported that confirmed reinfection was at a low level. Methods We modify the classical Susceptible-Exposed-Infectious-Recovered (SEIR) model with additional class for severe cases, vaccination and time-varying transmission rates. We fit the model to the severe acute respiratory infection (SARI) deaths, which is a proxy of the COVID-19 deaths, in 20 Brazilian cities with the large number of death tolls. We evaluate the vaccination effect by a contrast of "with" vaccination actual scenario and "without" vaccination in a counterfactual scenario. We evaluate the model performance when the reinfection is absent in the model. Results In the 20 Brazilian cities, the model simulated death matched the reported deaths reasonably well. The effect of the vaccination varies across cities. The estimated median IFR is around 1.2%. Conclusion Overall, through this modeling exercise, we conclude that the effects of vaccination campaigns vary across cites and the reinfection is not crucial for the second wave. The relatively high IFR could be due to the breakdown of medical system in many cities.
... In what follows, we will focus on vaccination, but similar considerations can be applied to natural infection. Of note, natural immunity confers at least similar (16) or longer-lasting and stronger protection against infection (17). Binding and neutralising antibodies are clearly associated with protection against infection (18,19). ...
Article
We provide an overview of how mathematical approaches unravel some key aspects of host-pathogen interactions. In the context of SARS-CoV-2, we discuss how these models have been useful to better characterise viral kinetics and its impact on infectiousness and disease progression, and how they can be used to predict the effects of pharmacological interventions.
Chapter
Critics of mRNA vaccines often share stories of people who got injured “from the jabs.” According to such reports, many have even died. Yet, public health (PH) officials and decision bodies keep asserting that these vaccines are safe. To those who have experienced adverse events (AEs), or who have close friends or family members who got injured or even passed post-vaccination, this seems incomprehensible. After all, it should be easy to prove that someone died or become severely injured from a medical intervention, one might think.
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Background COVID-19 has severely affected the elderly who are expected to display decreased immune responses due to immunosenescence. Methods This study retrospectively assesses neutralizing antibodies (NAb) productions up to 12 months(M) after infection in Long-term care patients. We used Roche diagnostics immunoassay to quantify anti-Spike(S) antibodies and a competitive immunoassay from Yhlo as a surrogate test for NAb. Results We included 91 patients, mean age 86 years. There was no significant variation of anti-S titers over time. There was a significant decrease of NAb titers between M3 and M6 but no further significant change up to M12. Overall, 75/91 (82%) and 52/91 (57%) patients had at least once anti-S titers >75 U/mL and NAb titers >50 AU/mL, respectively, corresponding to a significant neutralizing activity in vitro. All 68 patients studied at M12 had detectable anti-S antibodies and 60 (88%) had detectable NAb; 60/68 (88%) and 29/68 (42.6%) still had anti-S titers >75 U/mL and NAb titers >50 AU/mL. Higher NAb titers were correlated with severe infection, higher levels of CRP and lower lymphocyte counts. No patient developed reinfection. Conclusion Elderly people can display robust and persistent humoral response after SARS-CoV-2 infection, with NAb lasts up to 12 months.
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Compartmental models that dynamically divide the host population in categories such as susceptible, infected and immune constitute the mainstream of epidemiological modelling. Effectively such models treat infection and immunity as binary variables. We constructed an individual based stochastic model that considers immunity as a continuous variable and incorporates factors that bring about small changes in immunity. The small immunity effects (SIE) comprise cross immunity by other infections, small increments in immunity by sub clinical exposures and slow decay in the absence of repeated exposure. The model makes qualitatively different epidemiological predictions including repeated waves without the need for new variants, dwarf peaks (peak and decline of a wave much before reaching herd immunity threshold), symmetry in the upward and downward slopes of a wave, endemic state, new surges after variable and unpredictable gaps, new surge after vaccinating majority of population. In effect the SIE model raises alternative possible causes of the universally observed dwarf and symmetric peaks and repeated surges, observed particularly well during the Covid-19 pandemic. We also suggest testable predictions to differentiate between the alternative causes for repeated waves. The model further shows complex interactions of different interventions that can be synergistic as well as antagonistic. The model suggests that interventions that are beneficial in the short run can also be hazardous in the long run.
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Introduction: A precise estimate of the frequency and severity of SARS-CoV-2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta-analysis to evaluate the risk of reinfection and COVID-19 following primary infection. Methods: We searched MedLine, Scopus and preprint repositories for cohort studies evaluating the onset of new infections among baseline SARS-CoV-2-positive subjects. Random-effect meta-analyses of proportions were stratified by gender, exposure risk, vaccination status, viral strain, time between episodes, and reinfection definition. Results: Ninety-one studies, enrolling 15,034,624 subjects, were included. Overall, 158,478 reinfections were recorded, corresponding to a pooled rate of 0.97% (95% CI: 0.71%-1.27%), with no substantial differences by definition criteria, exposure risk or gender. Reinfection rates were still 0.66% after ≥12 months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3 months of Omicron wave, the reinfection rates reached 3.31%. Overall rates of severe/lethal COVID-19 were very low (2-7 per 10,000 subjects according to definition criteria), and were not affected by strain predominance. Conclusions: A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and healthcare needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low. The risk-benefit profile of multiple vaccine doses for this subset of population needs to be carefully evaluated.
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Infection with SARS‐CoV‐2, the etiology of the ongoing COVID‐19 pandemic, has resulted in over 450 million cases with more than 6 million deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from long‐lived plasma cells (LLPC) are the mainstay of most effective vaccines. However, ending the pandemic has been hampered by the lack of long‐lived immunity after infection or vaccination. Although immunizations offer protection from severe disease and hospitalization, breakthrough infections still occur, most likely due to new mutant viruses and the overall decline of neutralizing antibodies after 6 months. Here, we review the current knowledge of B cells, from extrafollicular to memory populations, with a focus on distinct plasma cell subsets, such as early‐minted blood antibody‐secreting cells and the bone marrow LLPC, and how these humoral compartments contribute to protection after SARS‐CoV‐2 infection and immunization.
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Background Both SARS-CoV-2 infection and COVID-19 vaccination contribute to population-level immunity against SARS-CoV-2. This study estimates the immunological exposure and effective protection against future SARS-CoV-2 infection in each US state and county over 2020-2021, and how this changed with the introduction of the Omicron variant. Methods We used a Bayesian model to synthesize estimates of daily SARS-CoV-2 infections, vaccination data and estimates of the relative rates of vaccination conditional on infection status to estimate the fraction of the population with (i) immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received one or more doses of a COVID-19 vaccine), (ii) effective protection against infection, and (iii) effective protection against severe disease, for each US state and county from January 1, 2020, to December 1, 2021. Results The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of December 1, 2021, was 88.2% (95% Credible Interval (CrI): 83.6%-93.5%). Accounting for waning and immune escape, effective protection against the Omicron variant on December 1, 2021, was 21.8% (95%CrI: 20.7%-23.4%) nationally and ranged between 14.4% (95%CrI: 13.2%-15.8%, West Virginia) to 26.4% (95%CrI: 25.3%-27.8%, Colorado). Effective protection against severe disease from Omicron was 61.2% (95%CrI: 59.1%-64.0%) nationally and ranged between 53.0% (95%CrI: 47.3%-60.0%, Vermont) and 65.8% (95%CrI: 64.9%-66.7%, Colorado). Conclusions While over four-fifths of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on December 1, 2021, only a fifth of the population was estimated to have effective protection against infection with the immune-evading Omicron variant.
Thesis
Les coronavirus sont des virus ARN enveloppés qui infectent les mammifères et les oiseaux. Chez l’homme, quatre coronavirus causent des maladies bénignes comme des rhumes et rhinites, HCoV-OC43, HCoV-229E, HCoV-NL63 et HCoV-HKU1. Au cours des deux dernières décennies, trois nouveaux coronavirus hautement pathogènes ont été identifiés, le SARS-CoV (« Severe Acute Respiratory Syndrome ») en 2003, le MERS-CoV (« Midle East Respiratory Syndrome ») en 2012 et récemment le SARS-CoV-2 en décembre 2019. La pandémie mondiale du COVID-19 a mis en évidence le manque d’antiviraux ciblant les coronavirus. Bien que de nombreux vaccins efficaces soient développés pour contrer la pandémie de COVID-19 due au SARS-CoV-2, il n’y a toujours aucun antiviral spécifique commercialisé contre ce virus et les traitements actuels consistent à traiter uniquement les symptômes.L’équipe du Dr Karin SERON du laboratoire de Virologie Moléculaire et Cellulaire du Centre d’Infection et d’Immunité de Lille s’est spécialisée dans l’identification d’antiviraux d’origine naturelle. En effet les plantes sont une source importante de molécules thérapeutiques et de nombreuses plantes sont encore utilisées aujourd’hui en médecine traditionnelle. L’objectif de ma thèse a été d’utiliser les connaissances et techniques développées par le laboratoire pour identifier des antiviraux naturels contre les coronavirus humains hautement pathogènes et de comprendre leurs mécanismes d’action. Mon premier projet a été réalisé en collaboration avec le groupe de Dr Simon Bordage du laboratoire de Pharmacognosie de la Faculté de Pharmacie de Lille dirigé par le Pr Sevser Sahpaz. Suite au criblage d’extraits de plantes, utilisées en médecine traditionnelle ivoirienne, contre le coronavirus HCoV-229E, nous avons sélectionné l’extrait de Mallotus oppositifollius qui était le plus actif. Après un fractionnement bioguidé, le principe actif a été isolé et identifié. Il s’agit du phéophorbide a (Pba). Le Pba inhibe HCoV-229E mais aussi les coronavirus hautement pathogènes MERS-CoV et SARS-CoV-2 (IC50 = 0,18 μM) ainsi que d’autres virus enveloppés par un mécanisme de photo-inactivation dynamique. Nous avons montré que le Pba cible la membrane virale et inhibe l’étape de fusion. Le Pba est le premier antiviral naturel possédant une activité virucide photo-dépendante décrite contre le SARS-CoV-2. Cette molécule pourrait potentiellement être utilisée en thérapie clinique ou comme désinfectant de surface. Mon deuxième projet porte sur une anthocyanidine, la delphinidine, déjà décrite par notre laboratoire comme antiviral contre le virus de l’hépatite C. Nous avons montré que la delphinidine inhibe de façon dose-dépendante l’entrée des coronavirus HCoV-229E, MERS-CoV et SARS-CoV-2 dans les cellules (IC50 = 16-20 μM). Nos résultats montrent que la delphinidine cible les sites de glycosylation de la protéine de surface S. Grâce à une collaboration avec le laboratoire de Chimie Bio-organique et Médicinale de Strasbourg, dirigé le Dr Mourad Elhabiri, nous avons criblé des dérivés de la delphinidine afin d’identifier des molécules plus actives. Nous avons ainsi identifié un composé actif contre le HCoV-229E à une concentration très faible (IC50 = 0,06 μM) mais qui semble avoir un mécanisme d’action différent de la delphinidine. En effet, il est actif à l’étape de réplication.En conclusion, au cours de ma thèse j’ai pu identifier de nouveaux antiviraux naturels contre les coronavirus humains et notamment le SARS-CoV-2 ayant des mécanismes d’action inédits. Ces travaux pourront servir de base à l’obtention de molécules pouvant être utilisées, dans l’avenir, pour le traitement des maladies à coronavirus.
Article
Relevance. Employees of a TB facility are a high-risk group for the incidence of COVID-19 due to their involvement in the detection and treatment of a new coronavirus infection, so vaccination of staff should play a significant role in their protection against a new coronavirus infection. Aim. Analyze the incidence of COVID-19 in employees of a large TB medical organization in a big city before and after mass immunization with anti-coronavirus vaccines. Materials & Methods. An analysis was made of the incidence of a new coronavirus infection COVID-19 among employees of the Moscow Research and Clinical Center for Tuberculosis Control during April 1, 2020–September 30, 2021, considering two periods of nine months in 2020 (2771 employees) and 2021 (2845 employees) and taking into account the data on the implementation of the first and second vaccinations carried out during the study period. Calculation of the average weekly and annual incidence per 1000 employees was carried out taking into account the different time spent by employees "at risk of getting sick". The incidence rate was calculated both for the entire study period as a whole and for weeks of high risk of COVID-19 incidence in the population of Moscow with an indicator of 500 or more per 100,000 population. Results. A comparative analysis of the incidence of COVID-19, registered from April 1, 2020 to October 1, 2021, was carried out among the average number of 2808 employees of the leading anti-TB institution in Moscow, taking into account vaccination. During the period under review, a total of 35.5% of employees in the institution fell ill and the annual incidence of staff was 177.4 per 1000 employees. 5.7% [95% CI 4.4–7.4%] of previously ill employees had a recurrence of the disease. Being unvaccinated until September 2020 and limitedly vaccinated until July 2021, the staff of the Center was massively immunized from July to August 2021 – up to 86.0% of the institution's staff by the end of the observation period. Based on the calculation of the weekly number of disease cases and of not yet ill persons among fully vaccinated, vaccinated with one drug, not vaccinated and previously ill, the incidence in these groups was compared, taking into account the time at risk of disease before a new case of COVID-19 was registered. For periods of high monthly incidence of the city's population (above 500 per 100 thousand), the annual notification rate of the unvaccinated was 2.8 times higher than that of the fully vaccinated (408.2 and 144.0 per 1000 people, RR = 2.8 [95% CI: 2.0–4.0]). The notification rate among those vaccinated with only one component of the two-component vaccine was 1.5 times higher than among those who were not vaccinated (271.5 and 409.2 per 1000 people. RR = 1.5 [95% CI: 1.04–2.2]). The probability of getting sick in fully vaccinated people was significantly higher than in those who previous infected with SARS-CoV-2 (144.0 and 78.0 per 1000 people, RR = 1.9 [95% CI: 1.1–3.1]). Conclusions. The obvious effectiveness of vaccination has been confirmed, including among the personnel of medical organizations directly involved in the fight against a new coronavirus infection.
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Importance Omicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. Objective To estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. Design Test-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. Setting Population-based, province of Quebec, Canada Participants Community-dwelling ≥12-year-olds tested for SARS-CoV-2. Exposures Prior laboratory-confirmed infection with/without mRNA vaccination. Outcomes Laboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results Without vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses. Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively). Conclusions and relevance Prior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.
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All South American countries from the Southern cone (Argentina, Brazil, Chile, Paraguay and Uruguay) experienced severe COVID-19 epidemic waves during early 2021 driven by the expansion of variants Gamma and Lambda, however, there was an improvement in different epidemic indicators since June 2021. To investigate the impact of national vaccination programs and natural infection on viral transmission in those South American countries, we analyzed the coupling between population mobility and the viral effective reproduction number Rt\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R_t$$\end{document}. Our analyses reveal that population mobility was highly correlated with viral Rt\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R_t$$\end{document} from January to May 2021 in all countries analyzed; but a clear decoupling occurred since May–June 2021, when the rate of viral spread started to be lower than expected from the levels of social interactions. These findings support that populations from the South American Southern cone probably achieved the conditional herd immunity threshold to contain the spread of regional SARS-CoV-2 variants circulating at that time.
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Доверие граждан старых демократий политикам, бюрократам и экспертам сослужило им плохую службу в ходе пандемии COVID-19. Поверив, что принудительные карантины (локдауны) и принуждение к вакцинации, никогда ранее не доказывавшие своей успешности, выбраны как наи- меньшее зло, и они, и их дети будут долго оплачивать счета непродуманной политики. Речь не идёт о нерациональном принятии решений политиками и бюрократами. Они принимают решения, руко- водствуясь своими интересами, а не интересами общества, в той мере, в какой общество им это позво- ляет. Поскольку личные права, свободы и частная собственность стали первопричиной и современ- ного экономического роста, и развития современной науки и медицины, призывы поступиться этими правами и свободами размывают основы некогда свободных, а потому богатых старых демократий. Да и моральная основа таких призывов вызывает большие сомнения.
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With the COVID-19 pandemic ongoing, accurate assessment of population immunity and the effectiveness of booster and enhancer vaccine doses is critical. We compare COVID-19-related hospitalization incidence rates in 2,412,755 individuals across four exposure levels: non-recent vaccine immunity (two BNT162b2 COVID-19 vaccine doses five or more months prior), boosted vaccine immunity (three BNT162b2 doses), infection-induced immunity (previous COVID-19 without a subsequent BNT162b2 dose), and enhanced infection-induced immunity (previous COVID-19 with a subsequent BNT162b2 dose). Rates, adjusted for potential demographic, clinical and health-seeking-behavior confounders, were assessed from July-November 2021 when the Delta variant was predominant. Compared with non-recent vaccine immunity, COVID-19-related hospitalization incidence rates were reduced by 89% (87–91%) for boosted vaccine immunity, 66% (50–77%) for infection-induced immunity and 75% (61–83%) for enhanced infection-induced immunity. We demonstrate that infection-induced immunity (enhanced or not) provides more protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less protection than booster vaccination. Additionally, our results suggest that vaccinating individuals with infection-induced immunity further enhances their protection. The relative degree of immunity to SARS-CoV-2 provided by combinations of natural infection, vaccination, and booster doses is unknown. Here, the authors show that infection-induced immunity provides more protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less than booster vaccination.
Article
World is still struggling with widespread dissemination and many unanswered questions about Coronavirus disease-19(COVID-19). Global efforts introduced several candidate vaccines against causing COVID-19, mostly requires require 2 doses of injections and some with about 90-95% efficacy. All strategies against the spread of infection are placed on breaking the chain of virus transmission though protective public health measures and mass vaccination, as yet. The current situation emphasis on the global need for carefully designed policies to maximize vaccine access and uptake. The risk compensation theory states that a drop in perceived risk caused by access to prevention measures may lead to an increase in risky behaviors. The current pandemic has faced people to the sense of risk compensation and behavior change in response to a perceived risk level. Risk compensation phenomenon may significantly defeat the benefits of COVID-19 vaccination, especially if the vaccine is not very effective in real life or in high-risk populations. Acknowledging and be conscious of Peltzman risk compensation has crucial importance in counteracting and neutralizing the false complacency of community also lend more weight to public health efforts. The public health messages and practices should be clearly expressed, straightforward, reliable and applicable. It is important that as efforts made to encourage mass vaccination of population other NPIs needs to be re-established and implemented to ensuring strike the balance of learning to live with COVID-19 in parallel with daily activities and job tasks.
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SARS-CoV-2 revisits a children’s fairy tale, the Emperor’s New Clothes. The swindler- salesmen are Biden, Fauci, et al. The magical clothes are their deliberate “pandemic of fear,” and the duped emperor is the American public. Extensive evidence is presented here of a great scam. The data details the true and low health risks of SARS-CoV-2; viral biology of natural immunity and the immune response from experimental mRNA gene therapy; side effects of the “jab;” and the draconian consequences of federal mandates. Differences between official pronouncements and scientific data are highlighted. The goal of the SARS-CoV-2 Big Con or scam is the nullification of the U.S. Bill of Rights in order to restore tyranny over the American public. We the People can fight for freedom with ballots and dollars.
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Introduction: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results: As of 25 September 2021, 245 of 1703 patients (14.3%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients were hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19-affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.
Article
We followed 106,349 primary care patients for 22,385,309 person-days across 21 calendar months. There were 69 breakthrough COVID-19 hospitalizations: 65/102,613(0.06%) among fully vaccinated, 3/11,047(0.03%) among those previously infected, and 1/7,313(0.01%) among those with both statuses. This data gives primary care providers real-world context regarding breakthrough COVID-19 hospitalization risk.
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Background: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. Results: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).
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SARS-CoV-2 Delta (B.1.617.2) variant of concern (VOC) and other VOCs are spreading in Europe. Micro-neutralisation assays with sera obtained after Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in 36 healthcare workers (31 female) demonstrated significant fold change reduction in neutralising titres compared with the original virus: Gamma (P.1) 2.3, Beta (B.1.351) 10.4, Delta 2.1 and 2.6. The reduction of the Alpha (B.1.1.7) variant was not significant. Despite being lower, remaining neutralisation capacity conferred by Comirnaty against Delta and other VOCs is probably protective.
Article
The present study describes a computerized registry of cardiovascular disease patients in a large health maintenance organization in Israel. The registry is aimed to be used by health professionals to identify cardiovascular disease patients and to follow the courses of their illnesses and risk factors. In 1998, the registry was initiated using advanced information technology that integrated personal computerized community and hospital records, data from laboratory tests, dispensed medications, physiological signals, radiological images, and reports from investigations and procedures. Between 1998 and 2007, the number of patients with cardiovascular diseases that were identified by the registry has increased from 34,144 to 80,339. During this period, the age-adjusted prevalence rates have risen from 3.7% to 5.1% and from 1.9% to 2.6%, among men and women, respectively. The percentage of ischemic heart disease patients who reached target LDL was doubled, from 21% in 2000 to 50% in 2006. The average stay in hospital declined from 11.7 to 8.6 days. Primary myocardial infarction rates declined 33% and 54% in men aged 54-65 and women aged 65-74 years, respectively. The present study provides, for the first time in Israel, data on selected quality of care and clinical outcomes using a large, population-based registry of cardiovascular disease patients. It demonstrates a significant improvement in the adherence with LDL tests and achieving target LDL levels and a subsequent decline in incidence of myocardial infarction within ten years since its establishment.