Covid19-Sources

Exposure to the virus in utero may have affected children’s development, according to a UCLA study, adding to a list of health problems emerging in the wake of the global pandemic.

Elevated incidence of type 2 diabetes after COVID-19 is greater, and persists for longer, in people who were hospitalised with COVID-19 than in those who were not, and is markedly less apparent in people who have been vaccinated against COVID-19. Testing for type 2 diabetes after severe COVID-19 and the promotion of vaccination are important tools in addressing this public health problem.

Intra-host diversity is an intricate phenomenon related to immune evasion, antiviral resistance, and evolutionary leaps along transmission chains. SARS-CoV-2 intra-host variation has been well-evidenced from respiratory samples. However, data on systemic dissemination and diversification are relatively scarce and come from immunologically impaired patients. Here, the presence and variability of SARS-CoV-2 were assessed among 71 tissue samples obtained from multiple organs including lung, intestine, heart, kidney, and liver from 15 autopsies with positive swabs and no records of immunocompromise. The virus was detected in most organs in the majority of autopsies. All organs presented intra-host single nucleotide variants (iSNVs) with low, moderate, and high abundances. The iSNV abundances observed within different organs indicate that the virus can mutate at one host site and subsequently spread to other parts of the body. In agreement with previous data from respiratory samples, our lung samples presented no more than 10 iSNVs each. But interestingly, when analyzing different organs we were able to detect between 11 and 45 iSNVs per case. Our results indicate that SARS-CoV-2 can replicate, and evolve in a compartmentalized manner, in different body sites, which agrees with the "viral reservoir" theory. We elaborate on how compartmentalized evolution in multiple organs may contribute to SARS-CoV-2 evolving so rapidly despite the virus having a proofreading mechanism.

To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detect…

Persistent symptoms among some individuals who develop COVID-19 have led to the hypothesis that SARS-CoV-2 might, in some form or location, persist for long periods following acute infection.1,2 Studies on SARS-CoV-2 persistence to date, however, have been limited by small and non-representative study populations, short durations since acute infection, unclear documentation of vaccination and reinfection histories, and the absence of a true negative comparator group to assess assay specificity (appendix p 2). To address these limitations, we evaluated the presence of SARS-CoV-2 antigens in once-thawed plasma from a well characterised group of 171 adults (appendix pp 3, 9) at several timepoints in the 14 months following RNA-confirmed SARS-CoV-2 infection, most of whom were studied before vaccination or reinfection (so-called pandemic-era participants).3 To understand the specificity of our findings, we compared them to 250 adults (appendix pp 3, 9) whose plasma was collected before 2020, who, by definition, were not infected with SARS-CoV-2 (pre-pandemic era). We used the Simoa (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens (appendix p 4).4,5 Of 660 pandemic-era specimens tested, 61 (9·2%) specimens from 42 participants (25% of the group), had one or more detectable SARS-CoV-2 antigens (figure A). The most commonly detected antigen was spike (n=33, 5·0%), followed by S1 (n=15, 2·3%) and N (n=15, 2·3%). Compared with the pre-pandemic era participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among the pandemic-era participants at all three timepoints in the post-acute phase of infection (figure B–E). The absolute difference in SARS-CoV-2 plasma antigen prevalence was +10·6% (95% CI +5·0 to +16·2) at 3·0–6·0 months post-onset of COVID-19; +8·7% (+3·1 to +14·3) at 6·1–10·0 months; and +5·4% (+0·42 to +10·3) at 10·1–14·1 months (appendix p 11).

ownload PDF Cite Share Set Alert Get Rights Reprints Previous article Next article mRNA-based vaccines, as shown by licensed COVID-19 vaccines, are immunogenic and can offer protection from severe disease with high efficacy.1,2 With the recent approval of a novel mRNA-based vaccine against human respiratory syncytial virus (mRESVIA; Moderna, Cambridge, MA, USA) by the US Food and Drug Administration and European Medical Agency, it is clear that mRNA-based vaccines will remain part of the future vaccine landscape. A self-amplifying RNA-based vaccine targeting ancestral SARS-CoV-2 was immunogenic as both a priming and booster vaccine in phase 3 trials.3,4 In a direct comparison with an mRNA-based vaccine, ARCT-154 induced superior neutralising antibody concentrations to omicron BA.5,4 highlighting the potential of self-amplifying RNA-based vaccines to induce stronger and broader antibody responses. In a follow-up report, Oda and colleagues5 showed that neutralising antibodies persist for at least 6 months after booster vaccination with a self-amplifying RNA-based vaccine. Both features are especially relevant as new, antigenically distinct SARS-CoV-2 variants continue to emerge and vaccine updates are required. In The Lancet Infectious Diseases, Yusuke Okada and colleagues6 report the results of a phase 3 trial evaluating an updated bivalent self-amplifying mRNA-based vaccine (ARCT-2301), targeting both the ancestral SARS-CoV-2 and the omicron BA.4/5 variant. In this double-blind, randomised, controlled, phase 3 clinical trial, the immunogenicity of booster vaccination with ARCT-2301 was compared with that of an mRNA-based BA.4/5 bivalent vaccine in fully vaccinated adults (ie, at least three previous vaccinations with mRNA-based vaccines; a total of 930 participants aged 19–80 years). 28 days after the booster vaccination, ARCT-2301-boosted individuals had superior neutralising antibody concentrations against ancestral SARS-CoV-2 and omicron BA.4/5 and higher neutralising antibody concentrations against omicron XBB.1.5 compared with those boosted with the mRNA-based vaccine. Compared with conventional mRNA-based vaccines, self-amplifying mRNA-based vaccines have the advantage of being immunogenic when administered at a low dose. In this trial, ARCT-2301 was administered at a 5-μg RNA dose, whereas the mRNA-based vaccine was given at 30 μg. The strong induction of neutralising antibodies by ARCT-2301, despite this lower dose, was probably caused by prolonged antigen production.7 The possibility of using lower doses with self-amplifying mRNA-based vaccines, combined with high-throughput production platforms, could substantially contribute to pandemic preparedness by allowing wider and more equitable distribution. Despite the proven immunogenicity of self-amplifying mRNA-based vaccines in multiple phase 3 clinical trials, even at a low dose, some questions remain unanswered. Most importantly, the clinical relevance of slightly higher neutralising antibody concentrations after self-amplifying mRNA-based vaccination is unclear, and efficacy studies have yet to be done. Additionally, in contrast to the well characterised antibody response, the cellular immune response induced by self-amplifying mRNA-based vaccines has been minimally characterised. It is unclear if mRNA-based and self-amplifying mRNA-based vaccines are mechanistically different in the way that immune responses are induced, or if the observed differences are mainly due to a difference in dose and antigen persistence. Follow-up studies comparing mRNA-based and self-amplifying mRNA-based vaccines would benefit from more in-depth immunological characterisation. Due to emergence of antigenically distinct SARS-CoV-2 variants, WHO currently recommends the use of updated monovalent COVID-19 vaccine formulations that are based on the circulating variant. Monovalent vaccines are preferred over bivalent formulations to prevent boosting of the immune response to ancestral SARS-CoV-2 and direct the immune response to the circulating variant.8 However, Okada and colleagues6 evaluated a bivalent formulation, and describe neutralising antibody concentrations to three SARS-CoV-2 variants, limiting insight into the breadth of the antibody response induced by the ARCT-2301 booster. It is essential to evaluate whether updated monovalent self-amplifying mRNA-based vaccines are capable of inducing SARS-CoV-2-specific immune responses to antigenically distinct variants, and whether these vaccines can redirect B-cell responses to novel variants by overcoming immune imprinting. Global acceptance rates of mRNA-based vaccines have varied since their introduction during the COVID-19 pandemic but are generally lower than those of conventional vaccines.9 The addition of a self-amplifying component to the vaccine landscape might further reduce acceptance rates of these vaccine types. With multiple self-amplifying mRNA-based vaccines in development6,10 it will be crucial to study acceptance rates of such vaccines and factors affecting those rates to maximise their potential. The combined clinical trials3,4,6 done by Arcturus Therapeutics with self-amplifying mRNA-based constructs show that these vaccines are immunogenic and can outperform mRNA-based vaccines when measuring neutralising antibody concentrations. It remains to be determined whether this finding is due to differences in dose and antigen persistence, or underlying mechanistical differences. However, the possibility to administer these vaccines at a low dose, combined with their adaptability, makes self-amplifying mRNA-based vaccines an attractive platform for emergency use. Confirming that self-amplifying mRNA-based vaccines have clinical efficacy and understanding the public acceptance of vaccines that contain self-amplifying nucleic acids could be the last steps towards licensure and widespread use.

In adults who had previously received three doses of an mRNA COVID-19 vaccine, immune responses 28 days after an ARCT-154 booster dose were non-inferior to those observed after a BNT162b2 booster dose for the Wuhan-Hu-1 strain of SARS-CoV-2 and superior for the Omicron BA.4/5 variant. Increased immune responses at 28 days might provide increased likelihood of protection against these strains during this period and could also result in longer duration of protection. Further studies will assess the immunogenicity induced against more recent SARS-CoV-2 variants.

Boosting mRNA-immunised adults with ARCT-2301 induced superior immunogenicity compared with Comirnaty BA.4-5 against both Wuhan-Hu-1 and omicron BA.4/5 variant COVID-19, and elicited a higher response against omicron XBB.1.5. Both vaccines had similar tolerability profiles. Self-amplifying mRNA vaccines could provide a substantial contribution to pandemic preparedness and response, inducing robust immune responses with a lower dose of mRNA to allow wider and more equitable distribution.

ownload PDF Cite Share Set Alert Get Rights Reprints Previous article Next article Of the many effective vaccines developed to combat the COVID-19 pandemic, the most notable were novel mRNA vaccines. Despite their high efficacy against the original Wuhan-Hu-1 strain and early SARS-CoV-2 variants, mRNA vaccines elicit a relatively short duration of immunity, exacerbated by immune evasion by variants leading to lower efficacy;1 for example, mRNA vaccine effectiveness against omicron declined to below 20% within 6 months of vaccination.2 Additionally, new variants are continuing to emerge,3 so the ongoing risk of COVID-19 outbreaks due to persistent viral circulation necessitates ongoing development of new vaccines to prolong vaccine-induced immunity, ideally for at least 1 year to meet new annual immunisation recommendations.3 We recently reported that a booster dose of the novel mRNA vaccine, ARCT-154 (Arcturus Therapeutics Holdings, San Diego, CA, USA), a self-amplifying mRNA (saRNA) vaccine based on the SARS-CoV-2 D614G variant (B.1), induced superior immunogenicity than BNT162b2 (Comirnaty; Pfizer–BioNTech) in BNT162b2-primed adults 1 month after administration.4 Commenting on our Article, Herfst and de Vries5 noted that “whether this [improvement in RNA vaccine technology] leads to better and longer-lasting immunity warrants further investigation”. In response, we present available ARCT-154 and BNT162b2 immunogenicity data at 3-months and 6-months post-booster until data showing responses at 12 months becomes available. In our study, Japanese adults who had been primed with two doses of mRNA vaccine and a booster dose of BNT162b2 at least 3 months earlier were randomly assigned equally to receive a second booster of either ARCT-154 (n=420) or BNT162b2 (n=408).4 In this extension analysis, we progressively excluded any participant who displayed seropositivity on days 1, 29, 91, or 181 for SARS-CoV-2 N-protein, considered to be indicative of COVID-19 infection, leaving 332 in the ARCT-154 group and 313 participants in the BNT162b2 group eligible for inclusion at the 6-month timepoint (appendix). Both groups had similar geometric mean surrogate virus neutralising titres (GMT) at baseline (GMT ratios were 0·94 for both Wuhan-Hu-1 and Omicron BA.4/5 SARS-CoV-2 variants). 1 month post-booster, the ARCT-154 group had the previously reported superior immunogenicity against both strains (figure A); GMTs against Wuhan-Hu-1 in the ARCT-154 group was 5390 (95% CI 4899–5931, n=378) and in the BNT162b2 group was 3738 (3442–4060, n=367), with a GMT ratio of 1·44 (95% CI 1·27–1·64). 3 months post-booster GMTs were 5928 (5414–6491, n=369) in the ARCT-154 group and 2899 (2648–3175, n=356) in the BNT162b2 group, a higher GMT ratio of 2·04 (1·80–2·32). Day 91 titres were equal to or greater than day 29 titres in 205 of 369 (55·6% [95% CI 50·3–60·7]) ARCT-154 recipients, but in only 108 of 356 (30·3% [25·6–35·4]) BNT162b2 recipients. Due to different rates of antibody waning by day 181 GMTs were 4119 (95% CI 3723–4557, n=332) in the ARCT-154 group and 1861 (1667–2078, n=313) in the BNT162b2 group, maintaining a GMT ratio of 2·21 (1·91–2·57) between vaccine groups. GMTs against Wuhan-Hu-1 remained higher 180 days after ARCT-154 than GMTs observed 28 days after the BNT162b2 booster.

Der CHMP hat zum Jahresende noch einige Arzneimittel zur Zulassung empfohlen, darunter zwei, die COVID-19 angehen: So gab der Ausschuss grünes Licht für Zapomeran (Kostaive), einen sich selbst verstärkenden mRNA-Impfstoff. Zudem empfahl er, den monoklonalen Antikörper Sipavibart (Kavigale) zur Vorbeugung von symptomatischem COVID-19 bei immungeschwächten Personen ab 12 Jahren zuzulassen.

This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms …

Fra i programmi CCM nati nel periodo della pandemia, quello qui presentato analizza gli effetti a lungo termine del COVID-19. Tramite uno studio di coorte, viene definita la dimensione del fenomeno, viene steso un documento di riferimento e definito un sistema di sorveglianza ad hoc.

ABSTRACTIntroduction. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on physical fitness in previously healthy adults

Journal of Neurology - SARS-CoV-2 antibodies in the cerebrospinal fluid (CSF) of COVID-19 patients possibly reflect blood-cerebrospinal fluid barrier (BCB) disruption due to systemic inflammation....

A positive-sense single-stranded RNA virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused the coronavirus disease 2019 (COVID-19) pandemic that devastated the world. While this is a respiratory virus, one feature of the SARS-CoV-2 infection was recognized to cause pathogenesis of other organs. Because the membrane fusion protein of SARS-CoV-2, the spike protein, binds to its major host cell receptor angiotensin-converting enzyme 2 (ACE2) that regulates a critical mediator of cardiovascular diseases, angiotensin II, COVID-19 is largely associated with vascular pathologies. In fact, we have previous reported that postmortem lung tissues collected from patients who died of COVID-19 exhibited thickened pulmonary vascular walls and reduced vascular lumen. The present study extended these findings by further characterizing the pulmonary vasculature of COVID-19 patients using larger sample sizes and providing mechanistic information through histological observations. The examination of 56 autopsy lung samples showed thickened vascular walls of small pulmonary arteries after 14 days of disease compared to H1N1 influenza patients who died before COVID-19 pandemic started. Pulmonary vascular remodeling in COVID-19 patients was associated with hypertrophy of the smooth muscle layer, perivascular fibrosis, edema and lymphostasis, inflammatory infiltration, perivascular hemosiderosis and neoangiogenesis. We found a correlation between the duration of hospital stay and the thickness of the muscular layer of pulmonary arterial walls. These results further confirm that COVID-19 affects the pulmonary vasculature and warrants an evaluation of patients that survived COVID-19 for possible future development of pulmonary arterial hypertension. ### Competing Interest Statement The authors have declared no competing interest.

This study examined the associations between psychopathy dimensions (triarchic phenotypes and classical factors), empathy domains (cognitive and affective), ...

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control ...

Here’s the latest news from the pandemic.

Nature Reviews Microbiology - In this Review, Sigal et al. explore SARS-CoV-2 persistence mechanisms, the frequency of persistent infections, their role in accelerated evolution and their link to...

Molecular Neurobiology - It has been more than three years since COVID-19 impacted the lives of millions of people, many of whom suffer from long-term effects known as long-haulers. Notwithstanding...

Most countries worldwide have experienced excess mortality that coincides temporally with the COVID-19 mass vaccination campaigns. This has led to speculation on the potential long-term effects of the vaccines on mortality risk. Methods: The study was designed as a retrospective cohort study, and included all individuals aged ≥18 years living in Norway during January 1, 2021, through December 31, 2023. Individuals were categorized as either unvaccinated (received no doses), partially vaccinated (received one or two doses) or fully vaccinated (received three or more doses) from the date of vaccination and onwards. Age-stratified Poisson models were used to estimate incidence rate ratios of death (all causes) between vaccination groups, adjusting for sex, calendar time, county of residence and risk group status (nursing home resident or preexisting condition with increased risk of severe COVID-19). Results: The study included 4 645 910 individuals (49.8% women) with 132 963 deaths during follow- up. There was a higher proportion of individuals that were part of a risk group among fully vaccinated individuals compared to unvaccinated individuals in all age groups, and a lower unadjusted rate of death: 51.5 vs 73.6 per 100 000 person years (py) among individuals aged 18-44 years, 295.1 vs 405.3 per 100 000 py among 45-64 years, and 3620.2 vs 4783.8 per 100 000 py among 65 years or older. The adjusted IRR of death for the same age groups were 0.42 (95% CI 0.38-0.47), 0.39 (95% CI 0.37-0.41) and 0.42 (95% CI 0.41-0.43), respectively. The differences in rate of death between vaccination groups were larger among men and peaked during 2022. Conclusion: Vaccinated individuals had a lower rate of all-cause death during 2021-2023 in Norway.

To date, 770 million people worldwide have contracted COVID-19, with many reporting long-term “brain fog”. Concerningly, young adults are both overrep…

Coronavirus Disease 2019 causes significant morbidity, and different variants of concern (VOCs) can impact organ systems differently. We conducted a single-center retrospective cohort analysis comparing biomarkers and clinical outcomes in hospitalized patients infected with the wild-type or Alpha (wt/Alpha) VOC against patients infected with the Omicron VOC. We included 428 patients infected with the wt/Alpha VOC and 117 patients infected with the Omicron VOC. The Omicron cohort had higher maximal median high-sensitivity Troponin-T (hs-TnT) levels (wt/Alpha: 12.8 ng/L, IQR 6.6–29.5 vs. Omicron: 27.8 ng/L, IQR 13.7–54.0; p 0.001) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (wt/Alpha: 256 ng/L, IQR 74.5–913.5 vs. Omicron: 825 ng/L, IQR 168–2759; p 0.001) levels. This remained true for patients under 65 years of age and without pre-existing cardiovascular disease (hs-TnT (wt/Alpha: 6.1 ng/L, IQR 2.5–10.25 vs. Omicron: 8.6 ng/L, IQR 6.2–15.7; p = 0.007) and NT-proBNP (wt/Alpha: 63 ng/L, IQR 25–223.75 vs. Omicron: 158 ng/L, IQR 75.5–299.5; p = 0.006)). In-hospital mortality was similar between the two groups (wt/Alpha: 53 or 12.7% vs. Omicron: 9 or 7.7%; p = 0.132) and more patients infected with wt/Alpha VOC required intensive care admission (wt/Alpha: 93 or 22.2% vs. Omicron: 14 or 12%; p = 0.014). Increased cardiac biomarkers were correlated with a higher risk of mortality and ICU admission in both groups. Herein, we detected higher levels of cardiac biomarkers in hospitalized patients infected with the Omicron VOC when compared to wt/Alpha, being indicative of higher cardiac involvement. Although hs-TnT and NT-proBNP levels were higher in the Omicron cohort and both markers were linked to in hospital mortality in both groups, the mortality rates were similar.

Das Leitsymptom von Patienten mit schwerem Long Covid und ME/CFS ist die post-exertionelle Malaise, kurz PEM. Sportmediziner Christian Puta erforscht die Mechan

In August more than one hundred writers, musicians and artists converged on Longyearbyen, the world’s northernmost town, before setting sail around Svalbard, a group of islands in the Arctic circle.

As of November 2024, SARS-CoV-2 Omicron JN.1 subvariants, such as KP.2 (JN.1.11.1.2), KP.3 (JN.1.11.1.3), KP.3.1.1 (JN.1.11.1.3.1.1), and XEC — a recombinant lineage between KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3) — have been circulating in several countries. To control the infection with SARS-CoV-2 Omicron JN.1 subvariants, JN.1 monovalent mRNA vaccines have been developed. Some previous reports showed that the JN.1 monovalent mRNA vaccine of Pfizer/BioNTech (US/Germany) increased antiviral humoral immunity against JN.1 subvariants and XEC. However, the efficacy of other available JN.1 monovalent mRNA vaccines (e.g., Daiichi-Sankyo, Japan) remains unassessed. To validate the antiviral efficacy induced by JN.1 mRNA vaccines, sera were collected from individuals vaccinated with Pfizer/BioNTech JN.1 mRNA vaccine (N=15) or Daiichi-Sankyo JN.1 mRNA vaccine (N=19) before and 3-4 weeks after vaccination. We then performed a neutralization assay using these sera and pseudoviruses. Both Pfizer/BioNTech JN.1 vaccine (2.4-to 8.0-fold, P=0.0001) and Daiichi-Sankyo JN.1 vaccine (2.3-to 13-fold, P=0.0001) boosted antiviral humoral immunity against all variants tested with statistical significance. While the Pfizer/BioNTech mRNA vaccine encodes the full-length JN.1 spike (S), the Daiichi-Sankyo mRNA vaccine encodes the receptor-binding domain of JN.1 S. Our data suggest that the receptor-binding domain of JN.1 S can effectively induce antiviral humoral immunity against JN.1 subvariants and XEC comparable to the full-length JN.1 S. However, it should be considered that the sizes of our cohorts are relatively small (20 donors per cohort), and donor characteristics, such as age, sex, underlying disease status, and previous SARS-CoV-2 infection, may critically affect the experimental results. Future investigations with larger cohorts will address this concern. When compared to vaccination with JN.1 mRNA vaccines, our previous investigations showed that the natural infection of JN.1 and KP.3.3 elicited poorer antiviral humoral immunity against JN.1 and its subvariants. Our results suggest that the JN.1 mRNA vaccination more robustly induces antiviral humoral immunity against recent JN.1 subvariants than the natural infection of JN.1 subvariants regardless of manufacturer. Moreover, as we reported last year, the humoral immunity induced by XBB.1.5 monovalent mRNA vaccine against XBB.1.5 was weaker than that against ancestral B.1.1. However, in the case of JN.1 monovalent mRNA vaccine, here we showed that the 50% neutralization titer against XBB.1.5 is greater than that against ancestral B.1.1. These observations imply that immune imprinting has shifted from that biased toward pre-Omicron to that biased toward Omicron, depending on the time and/or number of immune stimuli (e.g., infection and/or vaccination).

The SARS-CoV-2 JN.1 (BA.2.86.1.1) variant, arising from BA.2.86.1 with spike protein (S) substitution S:L455S, outcompeted the previously predominant XBB lineages by the beginning of 2024.1 Subsequently, JN.1 subvariants including KP.2 (JN.1.11.1.2) and KP.3 (JN.1.11.1.3), which acquired additional S substitutions (eg, S:R346T, S:F456L, and S:Q493E), have emerged concurrently (appendix pp 19–20).2,3 As of October 2024, KP.3.1.1 (JN.1.11.1.3.1.1), which acquired S:31del, outcompeted other JN.1 subvariants including KP.2 and KP.3, and is the most predominant SARS-CoV-2 variant in the world.4 Thereafter, XEC, a recombinant lineage of KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3), was first identified in Germany on Aug 7, 2024. XEC acquired two S substitutions, S:T22N and S:F59S, compared with KP.3 through recombination, with a breakpoint at genomic position 21 738–22 599 (appendix pp 19–20). We estimated the relative effective reproduction number (Re) of XEC using a Bayesian multinomial logistic model5 based on genome surveillance data from the USA, UK, France, Canada, and Germany, where this variant has spread as of August 2024 (appendix pp 19–20). In the USA, the Re of XEC is 1·13-fold higher than that of KP.3.1.1 (appendix pp 19–20). Additionally, the other countries under investigation herein showed higher Re for XEC compared with other variants. These results suggest that XEC has the potential to outcompete the other major SARS-CoV-2 lineages, including KP.3.1.1.4 Here, we assessed the virological properties of XEC using lentivirus-based pseudoviruses and HOS-ACE2/TMPRSS2 cells. Pseudovirus infection assay showed that the infectivity of KP.3.1.1 and XEC was statistically significantly higher than that of KP.3 (p0·001; appendix pp 19–20). Although S:T22N did not affect the infectivity of the pseudovirus based on KP.3, S:F59S statistically significantly increased it (p0·001; appendix pp 19–20). Neutralisation assay was performed using three types of human sera: convalescent sera after breakthrough infection (BTI) with XBB.1.5 or KP.3.3, and convalescent sera after JN.1 infection. In all serum groups, XEC showed immune resistance when compared with KP.3, with statistically significant differences (p0·02; appendix pp 19–20). In the cases of XBB.1.5 BTI sera and JN.1 infection sera, the 50% neutralisation titres (NT50) of XEC and KP.3.1.1 were comparable (appendix pp 19–20). However, in the case of KP.3.3 BTI sera, although the NT50 of KP.3 and KP.3.1.1 were comparable, the NT50 of XEC was significantly lower (p=0·01; 1·3-fold) than that of KP.3.1.1 (appendix pp 19–20). Moreover, both S:T22N (1·5-fold) and S:F59S (1·6-fold) significantly increased the resistance to KP.3.3 BTI sera (appendix p 19–20). Altogether, here we showed that XEC exhibited higher pseudovirus infectivity and higher immune evasion than KP.3. Particularly, XEC exhibited more robust immune resistance to KP.3.3 BTI sera than KP.3.1.1. Our data suggest that the higher Re of XEC than KP.3.1.1 is attributed to this property and XEC will be a predominant SARS-CoV-2 variant in the world in the near future.

Assays were performed with pseudoviruses harboring the S proteins of B.1.1, XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, HK.3, and BA.2.86. The following two sera were used: (A) vaccinated sera from fully vaccinated individuals who had not been infected (no infection before XBB.1.5 vaccination; 9 donors), (B) vaccinated sera from fully vaccinated individuals who had been infected with XBB subvariants after June, 2023 (XBB infection before XBB.1.5 vaccination; 10 donors). Sera were collected before vaccination (“Pre”) and 3–4 weeks after XBB.1.5 monovalent vaccination (“Post”). Assays for each serum sample were performed in triplicate to determine the 50% neutralisation titre (NT50). Each dot represents the NT50 value for each donor, and the NT50 values for the same donor before and after vaccination are connected by a line. Numbers in parentheses below the graphs indicate the geometric mean of the NT50 value. The horizontal dashed line indicates the detection limit (40-fold dilution). In (A), the number of the serum donors with the NT50 values below the detection limit is shown in the figure (below the horizontal dashed line). In (B), the numbers below the horizontal dashed line indicate the fold change of the NT50 value of the prevaccination of the XBB-infected cohort samples (B) compared with that of the infection-naive cohort samples (A). Statistically significant differences between prevaccination and postvaccination were determined by two-sided Wilcoxon signed-rank tests and are shown in red parentheses. The fold change of the reciprocal NT50 was calculated between prevaccination and postvaccination and is shown in red. Background information on the vaccinated donors is summarised in appendix p 5. The NT50 values of XBB.1.5 vaccine sera without infection (A) and XBB infection (B) are summarised in appendix p 6 and p 7.

Neurodegenerative diseases, particularly Alzheimer’s disease and other dementias as well as Parkinson’s disease, are emerging as profoundly significant challenges and burdens to global health, a trend highlighted by the most recent Global Burden of Disease (GBD) 2021 studies. This growing impact is closely linked to the demographic shift toward an aging population and the potential long-term repercussions of the COVID-19 pandemic, both of which have intensified the prevalence and severity of these conditions. In this review, we explore several critical aspects of this complex issue, including the increasing global burden of neurodegenerative diseases, unmet medical and social needs within current care systems, the unique and amplified challenges posed by the COVID-19 pandemic, and potential strategies for enhancing healthcare policy and practice. We underscore the urgent need for cohesive, multidisciplinary approaches across medical, research, and policy domains to effectively address the increasing burden of neurodegenerative diseases, thereby improving the quality of life for patients and their caregivers.