Post-acute sequelae after SARS-CoV-2 infection by viral variant and vaccination status: a multicenter cross-sectional study.

BACKGROUND: Disentangling the effects of SARS-CoV-2 variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS: We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in North-Eastern Switzerland. HCW were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCW without positive swab and with negative serology served as controls. The sum of eighteen self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyse the association of mean symptom number with viral variant and vaccination status. RESULTS: Among 2'912 participants (median age 44 years, 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number 1.12, p<0.001; median time since infection 18.3 months), after Alpha/Delta infection (0.67 symptoms, p<0.001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms, p=0.005; 3.1 months) compared to uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals, compared to 0.71 with 1-2 vaccinations (p=0.028) and 0.49 with ≥3 prior vaccinations (p=0.30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS: Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCW. Vaccination prior to Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.

Challenges and Recent Advancements in COVID-19 Vaccines.

Vaccination is the most effective method for the prevention of COVID-19 caused by SARS-CoV-2, which is still a global epidemic. However, the evolution of SARS-CoV-2 is so rapid that various variants, including the Alpha, Beta, Gamma, Delta, and Omicron variants, have emerged, lowering the protection rate of vaccines and even resulting in breakthrough infections. Additionally, some rare but severe adverse reactions induced by COVID-19 vaccines may raise safety concerns and hinder vaccine promotion; however, clinical studies have shown that the benefits of vaccination outweigh the risks caused by adverse reactions. Current vaccines approved with emergency use authorization (EUA) were originally adaptive for adults only, and infants, children, and adolescents are not included. New-generation vaccines are needed to overcome the challenges of limited adaptive age population, breakthrough infection (mainly due to virus variant emergencies), and critical adverse reactions. Fortunately, some advances in COVID-19 vaccines have been obtained regarding enlarged adaptive populations for clinical applications, such as the Pfizer/BioNTech vaccine and the Moderna vaccine. In this article, we provide a review on the challenges and recent advancements in COVID-19 vaccines. The development of next-generation COVID-19 vaccines should lay emphasis on the expansion of adaptive age populations in all individuals, the induction of immune responses to viral variants, the avoidance or alleviation of rare but potentially critical adverse reactions, and the discovery of subunit vaccines with adjuvants encapsulated in nanoparticles.

Interference reduction isothermal nucleic acid amplification strategy for COVID-19 variant detection.

Common reference methods for COVID-19 variant diagnosis include viral sequencing and PCR-based methods. However, sequencing is tedious, expensive, and time-consuming, while PCR-based methods have high risk of insensitive detection in variant-prone regions and are susceptible to potential background signal interference in biological samples. Here, we report a loop-mediated interference reduction isothermal nucleic acid amplification (LM-IR-INA) strategy for highly sensitive single-base mutation detection in viral variants. This strategy exploits the advantages of nicking endonuclease-mediated isothermal amplification, luminescent iridium(III) probes, and time-resolved emission spectroscopy (TRES). Using the LM-IR-INA strategy, we established a luminescence platform for diagnosing COVID-19 D796Y single-base substitution detection with a detection limit of 2.01 × 105 copies/µL in a linear range of 6.01 × 105 to 3.76 × 108 copies/µL and an excellent specificity with a variant/wild-type ratio of significantly less than 0.0625%. The developed TRES-based method was also successfully applied to detect D796Y single-base substitution sequence in complicated biological samples, including throat and blood, and was a superior to steady-state technique. LM-IR-INA was also demonstrated for detecting the single-base substitution D614G as well as the multiple-base mutation H69/V70del without mutual interference, indicating that this approach has the potential to be used as a universal viral variant detection strategy.

Masks, ventilation and exposure time: A web-based calculator of indoor COVID-19 infection risk

Two and half years into the COVID-19 pandemic, there is quite a lot of confusion over public health guidance necessary in order to reduce disease infection risks, from room air ventilation, the use of air cleaners, and type of mask and whether or not to wear a mask. This paper describes the development of a novel web-based calculator for use by the public to assess COVID-19 infection risks between a source and receiver in a typical room. The aim is to inform the disease infection risk in response to varying exposure times, mask-wearing, and viral variant in circulation. The calculator is based on the state-of-the-art research evidence, i.e., a room air ventilation model, mask infiltration efficiencies, room cleaner efficiencies, the quanta emission rates of various viral variants of COVID-19, and the modified Wells Riley equations. The results show that exposure times are critical in determining transmission risk. Masks are important and can reduce infection risk especially over shorter exposure times and for lower source emission quantum. N95 respirators are by far the most effective, especially for Omicron, and the results indicate that N95 respirators are necessary for the more infectious variants. Increasing fresh air ventilation rates from 2ac/h to 6ac/h can have a considerable impact in reducing transmission risk in a well-mixed space. Going from 6 ac/h to 12ac/h is less effective especially at lower exposure times. Venues can be classified in terms of risk, and appropriate high ventilation rates might be recommended for high-risk, speaking loudly and singing, such as classrooms and theatres. However, for low risk, quiet and speaking softly venues, such as offices and libraries, higher ventilation rates may not be required;instead, mechanical ventilation systems in combination with air cleaners can effectively remove small fraction size aerosol particles. The web-based calculator provides an easy-to-use and valuable tool for use in estimating infection risk.

Vaccination Rates and the Emergence of Viral Variants: An Evolutionary Strategies-Inspired Model

The emergence of variants of concern (VOC) has produced challenges in bringing the ongoing COVID-19 pandemic under control, and has created obstacles in the ultimate transition to endemicity;indeed, the omicron variant of SARS-CoV-2, the virus that causes COVID-19, caused a wave of unprecedented levels of infection throughout the globe. Although the available COVID-19 vaccines offer significant protection from infection, hospitalization, and death, challenges in vaccine availability globally have limited the efficacy of mass inoculation in controlling viral spread. The present study utilizes an evolutionary strategies (ES)-inspired model to examine the effect of vaccination upon the emergence of viral variants. The kinetics of the evolution of an idealized RNA virus are modelled in the details of the mutation of an ES population, and the emergence of variants is formulated as an optimization problem. A binary fitness function is optimized such that it achieves a maximum upon the condition that a single viral genome exhibits the requisite number of mutations such that it may be considered a variant of concern. Results demonstrate that vaccination is extremely effective in delaying the emergence of viral variants, and that vaccination rates are highly correlated with delayed variant emergence (R= 0.8399) and requisite viral genetic diversity for consideration as a variant of concern (R=0.8583). Time to emergence of a variant of concern for 0%, 25%, 50%, and 80% vaccination rates of the population are 17.46\pm 1.61 generations, 20.51\pm 2.12 generations, 33.67\pm 5.18 generations, and 226.12\pm 114.41 generations, respectively. It is shown that the delay in emergence of a variant of concern with higher vaccination rates may be attributable to a decrease in the number of infections, thus requiring a higher degree of genetic diversity in the viral genome. © 2022 IEEE.

SARS-CoV-2 variants and vulnerability at the global level.

Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have evolved. Viral variants may evolve with harmful susceptibility to the immunity established with the existing COVID-19 vaccination. These variants are more transmissible, induce relatively extreme illness, have evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and are more susceptible to re-infection. The Centers for Disease Control and Prevention (CDC) has categorized SARS-CoV-2 mutations as variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC). At the moment, four VOC and many variants of interest have been defined and require constant observation. This review article summarizes various variants of SARS-CoV-2 surfaced with special emphasis on VOCs that are spreading across the world, as well as several viral mutational impacts and how these modifications alter the properties of the virus.

Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains.

Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood. Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity. Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection. Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric. Funding: This work was supported by the Francis Crick Institute and the Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg.