Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic of coronavirus disease 2019 (COVID-19) that has led to more than 3 million deaths worldwide. Safe and effective vaccines are now available, including the mRNA-1273 prototype vaccine, which encodes for the Wuhan SARS-CoV-2 Spike protein stabilized in the prefusion conformation by 2 proline substitutions. This vaccine showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. Recently, SARS-CoV-2 variants have emerged, some of which have shown decreased susceptibility to neutralization by vaccine-induced antibody, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. In addition, recent evidence of waning antibody levels after infection or vaccination point to the need for periodic boosting of immunity. Here we present the preliminary evaluation of a clinical study on the use of the prototype mRNA-1273 or modified COVID-19 mRNA vaccines, designed to target emerging SARS-CoV-2 variants as booster vaccines in participants previously vaccinated approximately 6 months earlier with two doses of the prototype vaccine, mRNA-1273. The modified vaccines include a monovalent mRNA-1273.351 encoding for the S protein found in the B.1.351 variant and multivalent mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. As single 50 μg booster vaccinations, both mRNA-1273 and mRNA-1273.351 had acceptable safety profiles and were immunogenic. Antibody neutralization titers against B.1.351 and P.1 variants measured by SARS-CoV-2 pseudovirus neutralization (PsVN) assays before the booster vaccinations, approximately 6 to 8 months after the primary series, were low or below the assay limit of quantification, although GMTs versus the wild-type strain remained above levels likely to be protective. Two weeks after the booster vaccinations, titers against the wild-type original strain, B.1.351, and P.1 variants increased to levels similar to or higher than peak titers after the primary series vaccinations. Although both mRNA-1273 and mRNA-1273.351 boosted neutralization of the wild-type original strain, and B.1.351 and P.1 variants, mRNA-1273.351 appeared to be more effective at increasing neutralization of the B.1.351 virus versus a boost with mRNA-1273. The vaccine trial is ongoing and boosting of clinical trial participants with the multivalent mRNA-1273.211 is currently being evaluated.
Assembly and publication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome in January 2020 enabled the immediate development of tests to detect the new virus. This began the largest global testing programme in history, in which hundreds of millions of individuals have been tested to date. The unprecedented scale of testing has driven innovation in the strategies, technologies and concepts that govern testing in public health. This Review describes the changing role of testing during the COVID-19 pandemic, including the use of genomic surveillance to track SARS-CoV-2 transmission around the world, the use of contact tracing to contain disease outbreaks and testing for the presence of the virus circulating in the environment. Despite these efforts, widespread community transmission has become entrenched in many countries and has required the testing of populations to identify and isolate infected individuals, many of whom are asymptomatic. The diagnostic and epidemiological principles that underpin such population-scale testing are also considered, as are the high-throughput and point-of-care technologies that make testing feasible on a massive scale.
Authors: Christopher R. Berry, Anthony Fowler, Tamara Glazer, Samantha Handel-Meyer, Alec MacMillen
Date Added: May 4, 2021
Authors: Christopher R. Berry, Anthony Fowler, Tamara Glazer, Samantha Handel-Meyer, Alec MacMillen
We estimate the effects of shelter-in-place (SIP) orders during the first wave of the COVID-19 pandemic. We do not find detectable effects of these policies on disease spread or deaths. We find small but measurable effects on mobility that dissipate over time. And we find small, delayed effects on unemployment. We conduct additional analyses that separately assess the effects of expanding versus withdrawing SIP orders and test whether there are spillover effects in other states. Our results are consistent with prior studies showing that SIP orders have accounted for a relatively small share of the mobility trends and economic disruptions associated with the pandemic. We reanalyze two prior studies purporting to show that SIP orders caused large reductions in disease prevalence, and show that those results are not reliable. Our results do not imply that social distancing behavior by individuals, as distinct from SIP policy, is ineffective.
Background COVID‐19 vaccines can offer a route out of the pandemic, yet initial research suggests that many are unwilling to be vaccinated. A rise in the spread of misinformation is thought to have played a significant role in vaccine hesitancy. To maximize uptake, it is important to understand why misinformation has been able to take hold at this time and why it may pose a more significant problem within certain contexts. Objective To understand people's COVID‐19 beliefs, their interactions with (mis)information during COVID‐19 and attitudes towards a COVID‐19 vaccine. Design and Participants Bradford, UK, was chosen as the study site to provide evidence to local decision makers. In‐depth phone interviews were carried out with 20 people from different ethnic groups and areas of Bradford during Autumn 2020. Reflexive thematic analysis was conducted. Results Participants discussed a wide range of COVID‐19 misinformation they had encountered, resulting in confusion, distress and mistrust. Vaccine hesitancy could be attributed to three prominent factors: safety concerns, negative stories and personal knowledge. The more confused, distressed and mistrusting participants felt about their social worlds during the pandemic, the less positive they were about a vaccine. Conclusions COVID‐19 vaccine hesitancy needs to be understood in the context of the relationship between the spread of misinformation and associated emotional reactions. Vaccine programmes should provide a focused, localized and empathetic response to counter misinformation. Patient or Public Contribution A rapid community and stakeholder engagement process was undertaken to identify COVID‐19 priority topics important to Bradford citizens and decision makers.
In this paper, we focus on the camelid nanobodies as a revolutionary therapy that can guide efforts to discover new drugs for Coronavirus disease (COVID-19). The small size property makes nanobodies capable of penetrating efficiently into tissues and recognizing cryptic antigens. Strong antigen affinity and stability in the gastrointestinal tract allow them to be used via oral administration. In fact, the use of nanobodies as inhalant can be directly delivered to the target organ, conferring high pulmonary drug concentrations and low systemic drug concentrations and minimal systemic side effects. For that, nanobodies are referred as a class of next-generation antibodies. Nanobodies permit the construction of multivalent formats that may achieve ultra-high neutralization potency and then may prevent mutational escape and can neutralize a wide range of SARS-CoV-2 variants. Due to their distinctive characteristics, nanobodies can be of great use in the development of promising treatment or preventive strategies against SARS-CoV-2 infection. In this review, the state-of-the-art of camel nanobodies design strategies against the virus including SARS-CoV-2 are critically summarized. The application of general nanotechnology was also discussed to mitigate and control emerging SARS-CoV-2 infection.
Epidemiological studies revealed that the elderly and those with co-morbidities are most susceptible to COVID-19. To understand how genetics affects the risk of COVID-19, we conducted a multi-instrument Mendelian randomization analysis and found that the genetic variation that supports a longer life is significantly associated with the lower risk of COVID-19 infection. The odds ratio is 0.31 (95% CI: 0.18 to 0.52; P = 9.7× 10−6) per additional 10 years of life, and 0.53 (95% CI: 0.43 to 0.65; P = 2.3 × 10−9) per unit higher log odds of surviving to the 90th percentile. On the other hand, there was no association between COVID-19 susceptibility and healthspan (the lifespan free of the top seven age-related morbidities). We further applied aging clock models and detected an association between biological age acceleration and future incidence and severity of COVID-19 infection for all subjects as well as for individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. Finally, a bivariate genomic scan for age-related COVID-19 infection identified a key contribution of the Notch signaling pathway. Our analysis suggests that Notch2 expression is associated with a higher risk of COVID-19 infection, providing a druggable target. More generally, interventions that reduce biological age have the opportunity to reduce the risk of COVID-19.
Background The duration of humoral and T and cell response after the infection of SARS-CoV-2 remains unclear. Methods We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in COVID-19 patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. Results We enrolled 59 COVID-19 patients, including 38 moderate, 16 mild, and five asymptomatic patients; 31 (52.5%) were men, and 28 (47.5%) were women. The median age was 41 (interquartile range [IQR]: 30–55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable IgG antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor binding domain and surrogate virus-neutralizing antibodies. SARS-CoV-2-specific IgG + memory B cell and IFN-γ secreting T cell responses were detectable in over 70% of patients. Conclusions SARS-CoV-2-specific immune memory response persists in most patients nearly one year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.
Background: Treatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality. Findings: Between 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1.00; 95% confidence interval [CI] 0.93 to 1.07; p=0.93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66% vs. 67%; rate ratio 0.98; 95% CI 0.94-1.03, p=0.50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28% vs. 29%; rate ratio 0.99; 95% CI 0.93-1.05, p=0.79). Interpretation: Among patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 18ring late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades.