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(searched for: doi:10.1038/s41591-021-01446-y)
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, , Danielle A. Wagner, Sarah O’ Connell, Sandeep R. Narpala, Dillon R. Flebbe, Shayne F. Andrew, Rachel L. Davis, Barbara Flynn, Timothy S. Johnston, et al.
Abstract:
Neutralizing antibody responses gradually wane against several variants of concern (VOC) after vaccination with the SARS-CoV-2 vaccine mRNA-1273. We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted ~6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.β, which encompasses the spike sequence of the B.1.351 beta (β) variant. Following boost, animals had increased neutralizing antibody responses across all VOC, which was sustained for at least 8 weeks post-boost. Nine weeks following boost, animals were challenged with the SARS-CoV-2 β variant. Viral replication was low to undetectable in bronchoalveolar lavages and significantly reduced in nasal swabs in all boosted animals suggesting booster vaccinations may be required to sustain immunity and protection.
, Marcel Ballin, Anna Nordström
Published: 18 October 2021
The Lancet Regional Health - Europe; https://doi.org/10.1016/j.lanepe.2021.100249

Abstract:
The effectiveness of heterologous prime-boost Coronavirus disease 2019 (Covid-19) vaccination is currently unknown.
Published: 18 October 2021
by MDPI
Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines and antiviral agents against SARS-CoV-2 was a dire need. To date, various platforms have been utilized for SARS-CoV-2 vaccine development, and over 200 vaccine candidates have been produced, many of which have obtained the United States Food and Drug Administration (FDA) approval for emergency use. Despite this successful development and licensure, concerns regarding the safety and efficacy of these vaccines have arisen, given the unprecedented speed of vaccine development and the newly emerging SARS-CoV-2 strains and variants. In this review, we summarize the different platforms used for Coronavirus Disease 2019 (COVID-19) vaccine development, discuss their strengths and limitations, and highlight the major safety concerns and potential risks associated with each vaccine type.
, Juan Yang, Xiaowei Deng, Cheng Peng, Xinhua Chen, Qianhui Wu, Hengcong Liu, Juanjuan Zhang, Wen Zheng, Junyi Zou, et al.
Published: 17 October 2021
Abstract:
SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 85% of individuals aged ⩾12 years have been vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while children aged 0–11 years are currently not eligible for vaccination (as of September 2021). The aim of this work is to assess whether the importation of Delta variant infections will shift the COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate the epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years (as of September 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could lead to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the currently eligible age groups. The symptomatic SARS-CoV-2 infections and hospitalisation are projected to shift towards children and young adolescents, with 13% of symptomatic infections and 30% of hospitalisations occurring in those aged 0–11 years. Extending the vaccination roll-out to include children aged 3–11 years is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively), but would have a low impact on protecting infants (aged 0–2 years). Our findings highlight the need to strengthen vaccination efforts by simultaneously extending the target population and elevating vaccine effectiveness. Author summary Older age groups have the highest risk of severe illness and fatality from SARS-CoV-2 infection. While the vaccination coverage in China is highly skewed towards older age groups. No study has quantified to what extent the spread of Delta variant infections and lack of vaccination in younger age groups will shift the COVID-19 burden towards younger age groups and how this will affect the return to normal. To this end, we developed an age-structured transmission model to mimic the epidemics triggered by imported Delta variant infections in China. In the context of the vaccination programme targeting individuals aged ≥12 years as of September 2021, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections would lead to substantial disease burden, which will shift towards the 0–11-year age group. Extending the vaccination to children aged 3–11 years, for whom the currently available vaccines have been licensed, is projected to dramatically decrease symptomatic infections and hospitalisations within this age group but would have a low impact in protecting infants aged 0–2 years. This study highlights the value of extending vaccination to children aged 3–11 years and protecting infants 0–2 years by vaccinating their contacts.
Caroline Fenton,
Published: 15 October 2021
Drugs & Therapy Perspectives pp 1-11; https://doi.org/10.1007/s40267-021-00869-4

The publisher has not yet granted permission to display this abstract.
, Emma Pritchard, , , David W. Eyre, , , , John I. Bell, John N. Newton, et al.
Published: 14 October 2021
Abstract:
The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2.
Raghid Bsat, , , , Mohammad R. Hasan, , , Adeel A. Butt, , , et al.
Published: 7 October 2021
Abstract:
Background The effective reproduction number, R t , is a tool to track and understand epidemic dynamics. This investigation of R t estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the epidemic until August 18, 2021. Methods Real-time “empirical” was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. R was also estimated using a transmission dynamics model . Uncertainty and sensitivity analyses were conducted. Agreements between different R t estimates were assessed by calculating correlation coefficients. Results captured the evolution of the epidemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the B.1.1.7 variant. The various estimation methods produced consistent and overall comparable estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in epidemic dynamics. estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. correlated strongly with and provided an average . Conclusions R t estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for R t estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings.
Duaa W. Al-Sadeq, Farah M. Shurrab, Ahmed Ismail, Fathima Humaira Amanullah, Swapna Thomas, Nader Aldewik, Hadi M. Yassine, Hanan F. Abdul Rahim, Laith Abu-Raddad,
Published: 7 October 2021
Abstract:
Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, were granted the US Food and Drug Administration Emergency Use Authorization for preventing COVID-19. However, little is known about the difference in antibody responses induced by the two mRNA vaccines in naïve and individuals with a previous history of infections (PI group). Therefore, we investigated the levels of anti-S-RBD total antibodies (IgM, IgA, and IgG), anti-S-RBD IgG, and anti-S-RBD IgA in these two groups 1-13 (median=6) weeks following administration of two doses of mRNA-1273 or BNT162b2 vaccines. Results showed that in naïve-vaccinated group, the mRNA-1327 vaccine induces significantly higher levels of S-RBD total antibodies (3.5-fold; p<0.001), S-RBD IgG (2-fold-p<0.01), and S-IgA (2.1-fold, p<0.001) than the BNT162b2 vaccine. In the PI-vaccinated group, both vaccines produce significantly higher S-RBD total antibodies level than those of the naïve-vaccinated group. The PI group produced a higher level of S-RBD IgG than the naïve-BNT162b2 (p=0.05) but not more than the naïve-mRNA-1273 (p=0.9) group. Interestingly, the PI-vaccinated group produced a comparable level of IgA ratio to the naïve-mRNA-1273 group but significantly higher than the naïve-BNT162b2 group (1.6-fold, p<0.001). Our results showed that the mRNA-1327 vaccine is more immunogenic and induces a greater antibody response than the BNT162b2 vaccine.
, Jeff M Slezak, Heidi Fischer, Vennis Hong, Bradley K Ackerson, Omesh N Ranasinghe, Timothy B Frankland, Oluwaseye A Ogun, JoAnn M Zamparo, Sharon Gray, et al.
Published: 4 October 2021
The Lancet, Volume 398, pp 1407-1416; https://doi.org/10.1016/s0140-6736(21)02183-8

The publisher has not yet granted permission to display this abstract.
, Lina S. Sy, Lei Qian, Bradley K. Ackerson, Yi Luo, Gina S. Lee, Yun Tian, Ana Florea, Michael Aragones, Julia E. Tubert, et al.
Published: 1 October 2021
Abstract:
Background Real-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE. Methods We conducted a test-negative case-control study at Kaiser Permanente Southern California. Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021. Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date. Outcomes included SARS-CoV-2 infection and hospitalization. Exposures were 2 doses or 1 dose of mRNA-1273 ≥14 days prior to specimen collection versus no COVID-19 vaccination. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, adjusting for confounders. VE was calculated as (1-odds ratio)x100%. Results The study included 8,153 cases and their matched controls. Two-dose VE (95% confidence interval) was 86.7% (84.3-88.7%) against Delta infection, 98.4% (96.9-99.1%) against Alpha, 90.4% (73.9-96.5%) against Mu, 96-98% against other identified variants, and 79.9% (76.9-82.5%) against unidentified variants. VE against Delta declined from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Conclusions Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants. However, VE against Delta moderately declined with increasing time since vaccination. Trial Registration Number Not applicable Funding Moderna Inc.
Rita E. Chen, Matthew J. Gorman, Daniel Y. Zhu, Juan Manuel Carreño, Dansu Yuan, Laura A. VanBlargan, Samantha Burdess, Douglas A. Lauffenburger, Wooseob Kim, Jackson S. Turner, et al.
Published: 29 September 2021
Abstract:
SUMMARY Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against emerging variants of concern in this population. Here, we assessed a cohort of 74 CID patients treated as monotherapy with chronic immunosuppressive drugs for functional antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with Pfizer mRNA BNT162b2 vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with TNF-α inhibitors, and this pattern appeared worse against the B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of the majority of CID patients fell below the presumed threshold correlate for antibody-mediated protection. Thus, further vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population.
, Le Gao, Qingxin Zhou, ,
Published: 26 September 2021
Abstract:
Background It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC. Methods Published and preprinted randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, or Delta) were searched until 31 August 2021. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1− estimate). Results Seven RCTs (51,169 participants), 10 cohort studies (14,385,909 participants) and 16 case-control studies (734,607 cases) were included. Eight COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, and BBIBP-CorV) were included in this analysis. Full vaccination was effective against Alpha, Beta/Gamma, and Delta variants, with VE of 88.3% (95% CI, 82.4–92.2), 70.7% (95% CI, 59.9–78.5), and 71.6% (95% CI, 64.1–77.4), respectively. But partial vaccination was less effective, with VE of 59.0% (95% CI, 51.3–65.5), 49.3% (95% CI, 33.0–61.6), and 52.6% (95% CI, 43.3–60.4), respectively. mRNA vaccines seemed to have higher VE against VOC over others, significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. non-mRNA vaccines). Conclusions Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta/Gamma and Delta variants. Partial vaccination has less VE against VOC. mRNA vaccines seem to have higher VE against Alpha, Beta/Gamma, and Delta variants over others.
Melissa M Higdon, , , , , Anurima Baidya, Anjalika A Nande, Parisa A ShamaeiZadeh, Karoline K Walter, Daniel R Feikin, et al.
Published: 25 September 2021
Abstract:
Billions of doses of COVID-19 vaccines have been administered around the world, dramatically reducing SARS-CoV-2 incidence in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines as of August 2021. We included efficacy data from Phase 3 clinical trials for 13 vaccines within the WHO Emergency Use Listing evaluation process and real-world effectiveness for 5 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include effects against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for both partial and complete vaccination, and against SARS-CoV-2 variants of concern. In addition, we review the epidemiological principles behind the design and interpretation of vaccine effects and explain important sources of heterogeneity between studies.
Akira Takagi,
Published: 22 September 2021
Abstract:
COVID-19 vaccines are currently being administrated worldwide and playing a critical role in controlling the pandemic. They have been designed to elicit neutralizing antibodies against Spike protein of the original SARS-CoV-2, and hence they are less effective against SARS-CoV-2 variants with mutated Spike than the original virus. It is possible that novel variants with abilities of enhanced transmissibility and/or immunoevasion will appear in the near future and perfectly escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8+ cytotoxic T lymphocytes (CTLs). Several lines of evidence suggest the contribution of CTLs on the viral control in COVID-19, and CTLs target a wide range of proteins involving comparatively conserved non-structural proteins. Here, we identified twenty-two HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a (pp1a) of SARS-CoV-2 using computational algorithms, HLA-A*24:02 transgenic mice and the peptide-encapsulated liposomes. We focused on pp1a and HLA-A*24:02 because pp1a is relatively conserved and HLA-A*24:02 is predominant in East Asians such as Japanese. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by a number of mutations in the Sequence Read Archive database of SARS-CoV-2 variants. The information of such conserved epitopes might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any SARS-CoV-2 variants by the induction of both anti-Spike neutralizing antibodies and CTLs specific for conserved epitopes. Importance COVID-19 vaccines have been designed to elicit neutralizing antibodies against the Spike protein of the original SARS-CoV-2, and hence they are less effective against variants. It is possible that novel variants will appear and escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8+ cytotoxic T lymphocytes (CTLs). Here, we identified twenty-two HLA-A*24:02-restricted CTL candidate epitopes derived from the non-structural polyprotein 1a (pp1a) of SARS-CoV-2. We focused on pp1a and HLA-A*24:02 because pp1a is conserved and HLA-A*24:02 is predominant in East Asians. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by mutations in the database of SARS-CoV-2 variants. The information might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any variants.
Published: 22 September 2021
by MDPI
Abstract:
Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID-19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.
Published: 19 September 2021
by MDPI
Abstract:
Mass vaccination against the COVID-19 pandemic is ongoing worldwide to achieve herd immunity among the general population. However, little is known about how the COVID-19 vaccination would affect mental health and preventive behaviors toward the COVID-19 pandemic. In this study, we conducted a cross-sectional survey to address this issue among 4244 individuals at several COVID-19 vaccination sites in Guangzhou, China. Using univariate analysis and multiple linear regression models, we found that major demographic characteristics, such as biological sex, age, education level, and family per capita income, are the dominant influencing factors associated with health beliefs, mental health, and preventive behaviors. After propensity score matching (PSM) treatment, we further assessed the changes in the scores of health belief, mental health, and preventive behaviors between the pre-vaccination group and the post-vaccination group. When compared to individuals in the pre-vaccination group, a moderate but statistically significant lower score was observed in the post-vaccination group (p = 0.010), implying possibly improved psychological conditions after COVID-19 vaccination. In addition, there was also a moderate but statistically higher score of preventive behaviors in the post-vaccination group than in the pre-vaccination group (p< 0.001), suggesting a higher probability to take preventive measures after COVID-19 vaccination. These findings have implications for implementing non-pharmaceutical interventions combined with mass vaccination to control the rebound of COVID-19 outbreaks.
Published: 16 September 2021
by MDPI
Abstract:
The coronavirus disease 2019 (COVID-19) pandemic severely impacts health, economy, and society worldwide. Antiviral drugs against SARS-CoV-2 are urgently needed to cope with this global crisis. It has been found that the biogenesis and release mechanisms of viruses share a common pathway with extracellular vesicles (EVs). We hypothesized that small molecule inhibitors of EV biogenesis/release could exert an anti-SARS-CoV-2 effect. Here, we screened 17 existing EV inhibitors and found that calpeptin, a cysteine proteinase inhibitor, exhibited the most potent anti-SARS-CoV-2 activity with no apparent cytotoxicity. Calpeptin demonstrated the dose-dependent inhibition against SARS-CoV-2 viral nucleoprotein expression in the infected cells with a half-maximal inhibitory concentration (IC50) of 1.44 µM in Vero-E6 and 26.92 µM in Calu-3 cells, respectively. Moreover, calpeptin inhibited the production of infectious virions with the lower IC50 of 0.6 µM in Vero E6 cells and 10.12 µM in Calu-3 cells. Interestingly, a combination of calpeptin and remdesivir, the FDA-approved antiviral drug against SARS-CoV-2 viral replication, significantly enhanced the anti-SARS-CoV-2 effects compared to monotherapy. This study discovered calpeptin as a promising candidate for anti-SARS-CoV-2 drug development. Further preclinical and clinical studies are warranted to elucidate the therapeutic efficacy of calpeptin and remdesivir combination in COVID-19.
, Celine R. Gounder
Published: 16 September 2021
Nature Immunology, Volume 22, pp 1201-1203; https://doi.org/10.1038/s41590-021-01033-w

The publisher has not yet granted permission to display this abstract.
, Mahesh K.R. Kalikiri, Faheem Mirza, Sathyavathi Sundararaju, Anju Sharma, Thabisile Xaba, , , Reham A. El-Kahlout, Kin Ming Tsui, et al.
International Journal of Infectious Diseases, Volume 112, pp 52-54; https://doi.org/10.1016/j.ijid.2021.09.006

Abstract:
Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable samples, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive samples collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar.
Published: 7 September 2021
Abstract:
SARS-CoV-2 breakthrough infections have been increasingly reported in fully vaccinated individuals. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2, defined as 14 days after the second dose, against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice between February 1, 2021 and August 22, 2021. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. The primary population included 652 individuals who had a positive symptomatic test after full vaccination with BNT162b2 (cases) and 5,946 individuals with at least one negative symptomatic test after full vaccination (controls). The adjusted odds of symptomatic infection were higher 120 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.21, 95% confidence interval [CI]: 1.33-7.74). Importantly, the odds of infection were still lower 150 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.3, 95% CI: 0.19-0.45), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of experiencing a non-COVID-19 hospitalization decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. Taken together, these data constitute an early signal for waning protection against symptomatic illness while also providing reassurance that BNT162b2 continues to protect against symptomatic SARS-CoV-2 infection several months after full vaccination. Continued surveillance of COVID-19 vaccine durability, particularly against severe disease, is critical to guide effective and equitable strategies to respond to the pandemic, including distribution of booster doses, development of new vaccines, and implementation of both pharmaceutical and nonpharmaceutical interventions.
Venice Servellita, Alicia Sotomayor-Gonzalez, Amelia S. Gliwa, Erika Torres, Noah Brazer, Alicia Zhou, Katherine T. Hernandez, Madeline Sankaran, Baolin Wang, Daniel Wong, et al.
Published: 25 August 2021
Abstract:
Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity only (N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 – 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results suggest that vaccine breakthrough infecions are overrepresnted by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.
, Emma Pritchard, , , David W. Eyre, Karina-Doris Vihta, , Jodie Hay, John I Bell, John N Newton, et al.
Published: 24 August 2021
Abstract:
The effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. We investigated the effectiveness of the vaccines in a large community-based survey of randomly selected households across the UK. We found that the effectiveness of BNT162b2 and ChAd0x1 against any infections (new PCR positives) and infections with symptoms or high viral burden is reduced with the Delta variant. A single dose of the mRNA-1273 vaccine had similar or greater effectiveness compared to a single dose of BNT162b2 or ChAdOx1. Effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity following second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positives but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher among those vaccinated following a prior infection and younger adults. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.
Hannah Chung, Siyi He, Sharifa Nasreen, Maria E Sundaram, Sarah A Buchan, Sarah E Wilson, Branson Chen, Andrew Calzavara, Deshayne B Fell, Peter C Austin, et al.
Published: 20 August 2021
by BMJ
Abstract:
Objective To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). Design Test negative design study. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. Interventions BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Main outcome measures Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. Results Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. Conclusions Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.
Elisabeth Mahase
Published: 19 August 2021
by BMJ
Abstract:
Eight notable variants of SARS-CoV-2 have been found since September 2020. Elisabeth Mahase reviews the line-up so far
Ryan S. McGee, Julian R. Homburger, Hannah E. Williams, ,
Published: 18 August 2021
Abstract:
During the initial stages of the COVID-19 pandemic, many workplaces and universities implemented institution-wide proactive testing programs of all individuals, ir-respective of symptoms. These measures have proven effective in mitigating outbreaks. As a greater fraction of the population becomes vaccinated, we need to understand what continued benefit, if any, proactive testing can contribute. Here, we address this problem with two distinct modeling approaches: a simple analytical model and a more simulation using the SEIRS+ platform. Both models indicate that proactive testing remains useful until a threshold level of vaccination is reached. This threshold depends on the transmissibility of the virus and the scope of other control measures in place. If a community is able to reach the threshold level of vaccination, testing can cease. Otherwise, continued testing will be an important component of disease control. Because it is usually difficult or impossible to precisely estimate key parameters such as the basic reproduction number for a specific workplace or other setting, our results are more useful for understanding general trends than for making precise quantitative predictions.
, , , , , Hebah A. Al Khatib, , Mohammad R. Hasan, , Sawsan AlMukdad, et al.
Published: 4 August 2021
Abstract:
Severity (acute-care hospitalization), criticality (ICU hospitalization), and fatality of SARS-CoV-2 Beta (B.1.351) variant was investigated through case-control studies applied to complete national cohorts of infection, disease, and death cases in Qatar. Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Findings highlight risks to healthcare systems, particularly to intensive care facilities and resources, with increased circulation of Beta.
Karin Bok, Sandra Sitar, Barney S. Graham,
Published: 2 August 2021
Immunity, Volume 54, pp 1636-1651; https://doi.org/10.1016/j.immuni.2021.07.017

Abstract:
Summary The development of effective vaccines to combat infectious diseases is a complex multi-year and multi-stakeholder process. To accelerate the development of vaccines for coronavirus disease 2019 (COVID-19), a novel pathogen emerging in late 2019 and spreading globally by early 2020, the United States government (USG) mounted an operation bridging public and private sector expertise and infrastructure. The success of the endeavor can be seen in the rapid advanced development of multiple vaccine candidates, with several demonstrating efficacy and now being administered around the globe. Here, we review the milestones enabling the USG-led effort, the methods utilized, and ensuing outcomes. We discuss the current status of COVID-19 vaccine development and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.
Published: 30 July 2021
Abstract:
SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigated differences in RT-qPCR Ct values across Qatar’s national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Through matched-cohort analyses of the randomly diagnosed infections, the mean Ct value was higher in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value was 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.8-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.4-4.6) cycles higher for reinfections in unvaccinated individuals. Assuming a linear relationship between viral load and infectiousness, these differences imply that breakthrough infections are at least 50% less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.
Published: 26 July 2021
Abstract:
Effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood. Here, we investigated whether persons vaccinated after a prior infection have better protection against future infection than those vaccinated without prior infection. Effect of prior infection was assessed in Qatar’s population, where the Alpha (B.1.1.7) and Beta (B.1.351) variants dominate incidence, using two national retrospective, matched-cohort studies, one for the BNT162b2 (Pfizer-BioNTech) vaccine, and one for the mRNA-1273 (Moderna) vaccine. Incidence rates of infection among BNT162b2-vaccinated persons, with and without prior infection, were estimated, respectively, at 1.66 (95% CI: 1.26-2.18) and 11.02 (95% CI: 9.90-12.26) per 10,000 person-weeks. The incidence rate ratio was 0.15 (95% CI: 0.11-0.20). Analogous incidence rates among mRNA-1273-vaccinated persons were estimated at 1.55 (95% CI: 0.86-2.80) and 1.83 (95% CI: 1.07-3.16) per 10,000 person-weeks. The incidence rate ratio was 0.85 (95% CI: 0.34-2.05). Prior infection enhanced protection of those BNT162b2-vaccinated, but not those mRNA-1273-vaccinated. These findings may have implications for dosing, interval between doses, and potential need for booster vaccination.
, Jan Michler, , , Patrick Taeschler, Miro E. Raeber, , Jakob Nilsson, ,
Published: 22 July 2021
Abstract:
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen1,2. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells3. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8+ T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting one year after acute infection re-express CD45RA and interleukin-7 receptor α (CD127), upregulate T cell factor-1 (TCF1), and maintain low CCR7, thus resembling CD45RA+ effector-memory T (TEMRA) cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clone contraction and disappearance. Collectively, we identify a transcriptional signature differentiating short-from long-lived memory CD8+ T cells following an acute virus infection in humans.
, Mahesh K. R. Kalikiri, Faheem Mirza, Sathyavathi Sundararaju, Anju Sharma, Stephan Lorenz, Hiam Chemaitelly, Reham A. El-Kahlout, Kin Ming Tsui, Hadi M. Yassine, et al.
Published: 22 July 2021
Abstract:
Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable samples, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive samples collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar.
, Hannah Chung, Siyi He, Kevin A. Brown, Jonathan B. Gubbay, Sarah A. Buchan, Deshayne B. Fell, Peter C. Austin, Kevin L. Schwartz, Maria E. Sundaram, et al.
Published: 3 July 2021
Abstract:
SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax), and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection ≥7 days after two doses was 89–92% against Alpha, 87% against Beta, 88% against Gamma, 82–89% against Beta/Gamma, and 87–95% against Delta across vaccine products. The corresponding estimates ≥14 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults (≥60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.
Hannah Chung, Siyi He, , Maria E. Sundaram, Sarah A. Buchan, Sarah E. Wilson, Branson Chen, Andrew Calzavara, Deshayne B. Fell, Peter C. Austin, et al.
Published: 28 May 2021
Abstract:
Objectives To estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design We applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants Community-dwelling adults aged ≥16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. Interventions Pfizer-BioNTech’s BNT162b2 or Moderna’s mRNA-1273 vaccine. Main outcome measures Laboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection. Results Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received ≥1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14–20 days after the first dose to 71% (95%CI, 63 to 78%) at 35–41 days. VE ≥7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE ≥14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14–20 days to 91% (95%CI, 73 to 97%) at ≥35 days, whereas VE ≥7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged ≥70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants. Conclusions Two doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.
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