scholarly journals SARS-CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients

Author(s):  
Vimvara Vacharathit ◽  
Pakorn Aiewsakun ◽  
Suwimon Manopwisedjaroen ◽  
Chanya Srisaowakarn ◽  
Thanida Laopanupong ◽  
...  

Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine- and infection- induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decisionmakers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 742
Author(s):  
José Javier Morales-Núñez ◽  
José Francisco Muñoz-Valle ◽  
Carlos Meza-López ◽  
Lin-Fa Wang ◽  
Andrea Carolina Machado Sulbarán ◽  
...  

The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).


2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Maysoon Dahab ◽  
Kevin van Zandvoort ◽  
Stefan Flasche ◽  
Abdihamid Warsame ◽  
Ruwan Ratnayake ◽  
...  

Abstract COVID-19 prevention strategies in resource limited settings, modelled on the earlier response in high income countries, have thus far focused on draconian containment strategies, which impose movement restrictions on a wide scale. These restrictions are unlikely to prevent cases from surging well beyond existing hospitalisation capacity; not withstanding their likely severe social and economic costs in the long term. We suggest that in low-income countries, time limited movement restrictions should be considered primarily as an opportunity to develop sustainable and resource appropriate mitigation strategies. These mitigation strategies, if focused on reducing COVID-19 transmission through a triad of prevention activities, have the potential to mitigate bed demand and mortality by a considerable extent. This triade is based on a combination of high-uptake of community led shielding of high-risk individuals, self-isolation of mild to moderately symptomatic cases, and moderate physical distancing in the community. We outline a set of principles for communities to consider how to support the protection of the most vulnerable, by shielding them from infection within and outside their homes. We further suggest three potential shielding options, with their likely applicability to different settings, for communities to consider and that would enable them to provide access to transmission-shielded arrangements for the highest risk community members. Importantly, any shielding strategy would need to be predicated on sound, locally informed behavioural science and monitored for effectiveness and evaluating its potential under realistic modelling assumptions. Perhaps, most importantly, it is essential that these strategies not be perceived as oppressive measures and be community led in their design and implementation. This is in order that they can be sustained for an extended period of time, until COVID-19 can be controlled or vaccine and treatment options become available.


2021 ◽  
Author(s):  
Chotiwat Seephetdee ◽  
Nattawut Buasri ◽  
Kanit Bhukhai ◽  
Kitima Srisanga ◽  
Suwimon Manopwisedjaroen ◽  
...  

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistically friendly are critically needed for global equity, especially for middle to low income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported with the use of the receptor binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, so called "HexaPro", has been shown for its physical property to possess two RBD in the "up" conformation, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminium hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. In addition, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.


2021 ◽  
Author(s):  
Matilda Emgård ◽  
Rose Mwangi ◽  
Celina Mayo ◽  
Ester Mshana ◽  
Gertrud Nkini ◽  
...  

Abstract BackgroundAntibiotic resistance is a threat to global child health. Primary healthcare workers play a key role in antibiotic stewardship in the community, but few studies in low-income countries have described their experiences of initiating antibiotic treatment in children. Thus, the present study aimed to describe primary healthcare workers’ experiences of antibiotic prescription for children under five years of age and their conceptions of antibiotic resistance in Northern Tanzania.MethodsA qualitative study involving individual in-depth interviews with 20 prescribing primary healthcare workers in Moshi urban and rural districts, Northern Tanzania, was performed in 2019. Interviews were transcribed verbatim, translated from Kiswahili into English and analysed according to the phenomenographic approach.FindingsFour conceptual themes emerged during the analysis; conceptions in relation to the prescriber, the mother and child, other healthcare actors and in relation to outcome. The healthcare workers relied mainly on clinical examination and medical history provided by the mother to determine the need for antibiotics. Confidence in giving advice concerning non-antibiotic treatment varied among the participants and expectations of antibiotic treatment were perceived to be common among the mothers. Antibiotic resistance was mainly perceived as a problem for the individual patient who was misusing the antibiotics.ConclusionsTo increase rational antibiotic prescription, an awareness needs to be raised among Tanzanian primary healthcare workers of the threat of antibiotic resistance, not only to a few individuals, but to public health. Guidelines on childhood illnesses should be updated with advice concerning symptomatic treatment when antibiotics are not necessary, to support rational prescribing practices and promote trust in the clinician and mother relationship.


2020 ◽  
Author(s):  
Abhinay Gontu ◽  
Sreenidhi Srinivasan ◽  
Eric Salazar ◽  
Meera Surendran Nair ◽  
Ruth H. Nissly ◽  
...  

ABSTRACTThe optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determined in vitro live-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers ≥160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score.One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nikolaos Kapitsinis

Abstract Background Government responses to the pandemic varied in terms of timing, duration, and stringency, seeking to protect healthcare systems, whose pre-pandemic state varied significantly. Therefore, the severity of Covid-19 and, thus, excess mortality have been unequal across counties. This paper explores the geography of excess mortality and its underlying factors in 2020, highlighting the effects of health policies pre-pandemic and strategies devised by governments to cope with Covid-19. Methods Excess mortality is estimated for 79 high, medium and low-income countries. The factors of excess mortality are examined employing median quantile regression analysis. Results Health privatization, healthcare underfunding, and late implementation of containment and mitigation strategies were powerful drivers of excess mortality. By contrast, the results suggest a negative association of excess mortality with health expenditure, number of doctors and hospital beds, share of population covered by health insurance and test and trace capacity. Conclusions The evidence highlights the importance of sufficiently funded healthcare systems with universal access and strong primary healthcare in the battle against the pandemic. An early response to Covid-19, including borders’ controls and a strong test and trace capacity, could improve epidemiological surveillance and minimize excess mortality, with stringent and lengthy lockdowns not providing a significant benefit.


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 498
Author(s):  
Chotiwat Seephetdee ◽  
Nattawut Buasri ◽  
Kanit Bhukhai ◽  
Kitima Srisanga ◽  
Suwimon Manopwisedjaroen ◽  
...  

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistic-friendly are critically needed for global equity, especially for middle- to low-income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported using the receptor-binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, named HexaPro, has been shown to possess two RBD in the “up” conformation, due to its physical property, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for the SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminum hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. Also, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.


2021 ◽  
Vol 7 ◽  
Author(s):  
Yazan Nedal Alhalaseh ◽  
Hatem A. Elshabrawy ◽  
Madiha Erashdi ◽  
Mohammed Shahait ◽  
Abdulrahman Mohammad Abu-Humdan ◽  
...  

The shortage of healthcare providers is well-documented in low-income countries (LIC) prior to COVID-19, due to various causes including the migration to developed countries, scarcity of supplies, poor healthcare infrastructure, limited ICU facilities, and lack of access to guidelines and protocols. One of the important hitches in LIC is the insufficient testing capacity that precluded accurate assessment of disease burden and subsequently resource allocations. Trying to adhere to the principles of bioethics including respect to others, beneficence, and justice should be applied on the ground in the particular setting of the LIC. Solutions should be tailored to the tangible needs and possibility of implementation in real life in the face of the “already” limited resources by making use of simple, yet plausible, measures. Implementing guidelines and frameworks that were set to work in the better-resourced nations is a call for futility. The adoption of novel solutions to overcome the unique challenges in the LIC is exigent. These include the use of automated screening algorithms and virtual video clinics. Moreover, integrating electronic intensive care unit (e-ICU) software may allow for remote monitoring of multiple patients simultaneously. Telemedicine could help in getting consultations worldwide. It can also enhance healthcare workers' knowledge and introduce new skills through teleconferences, e-workshops, and free webinars. Healthcare workers can be remotely trained to enhance their skills. Agencies, such as the WHO, should develop comprehensive programs to tackle different health issues in LIC in collaboration with major institutions and experts around the world.


2021 ◽  
Author(s):  
Daniel Junker ◽  
Alex Dulovic ◽  
Matthias Becker ◽  
Teresa R Wagner ◽  
Philipp D Kaiser ◽  
...  

As global vaccination campaigns against SARS-CoV-2 proceed, there is emerging interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. To assess neutralizing capacity, we developed a bead-based multiplex ACE2 RBD competition assay as a large scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and RBD, this assay detects the presence of Nabs against SARS-CoV2 in serum. Using this multiplex approach allows the simultaneous analysis of Nabs against all SARS-CoV-2 variants of concern and variants of interest in a single well. Following validation, we analyzed 325 serum samples from 186 COVID-19 patients of varying severity. Neutralization capacity was reduced for all variants examined compared to wild-type, especially for those displaying the E484K mutation. The neutralizing immune response itself, while highly individualistic, positively correlates with IgG levels. Neutralization capacity also correlated with disease severity up to WHO grade 7, after which it reduced.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255807
Author(s):  
Haydee Miranda-Ortiz ◽  
Edith A. Fernández-Figueroa ◽  
Erika B. Ruíz-García ◽  
Anallely Muñoz-Rivas ◽  
Alejandra Méndez-Pérez ◽  
...  

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.


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