SARS-CoV-2 と COVID-19 に関する備忘録 Vol.20――Long Covidを負った人のQOLは重度の癌や多発性硬化症患者と同程度まで低下、SARS-CoV-2コロナウイルスが免疫による選択圧が存在しなくても確率論ドライブで変異し続けている…etc.

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録


◆NZ must prepare for Long Covid implications, researcher warns【Radio New Zealand：Krystal Gibbens　2023年11月1日】

Interim results from New Zealand’s Long Covid Registry show support measures are lacking and people are going to work while unwell.

The study, conducted in collaboration with Long Covid Support Aotearoa and the University of Auckland, with funding from the Ministry of Health, is the first quantitative research of New Zealanders with Long Covid.

Research lead Dr Paula Lorgelly said one of the advantages of this study was that it looked at cases of Long Covid from more recent Covid variants.

The study looked at a range of health and wellbeing factors experienced by Long Covid sufferers.

Quality of life was measured using the globally renowned EQ-5D questionnaire. Lorgelly said the mean score for participants before Covid was 0.88, fairly standard for New Zealanders.

“Now with Long Covid, they’re reporting a mean score of 0.529. And that is similar to people who have severe cancer and severe MS,” she said.

The study also surveyed the symptoms that those with Long Covid were experiencing.

“Individuals are reporting mostly experiencing fatigue, quite a lot of fatigue in the population, a lot of brain fog, loss of concentration, and a fair amount of kind of sleep disturbance and sleep issues.”

About 45 percent of the sample said they had experienced a decline in their income and many were no longer able to manage a 40-hour working week. And 34 percent reported they had used up their sick leave, whereas 65 percent have had to take time off work and 50 percent reduce their work hours.

Seventy-two percent were going to work despite being unwell.

Lorgelly said the study showed it was a debilitating condition, and the results were fairly similar to studies overseas.

She said it had results from 868 individuals so far, but not all participants had completed all modules.

She said the study had been designed in modules so participants who were experiencing symptoms such as fatigue and brain fog could fill it in when they were able.

Wide-ranging implications to MSD, ACC

Lorgelly hoped the Ministry of Health would acknowledge that even with less severe waves of infection and a highly vaccinated population, it was a chronic condition and warranted the delivery of health services.

But it was not just the Ministry of Health she thought should take notice.

“[The Ministry of Business, Innovation and Employment] should be interested because it’s going to have a huge productivity effect. [The Ministry of Social Development] should be interested because of the impact on benefits, etc.”

Long Covid advocate Jenene Crossan said it could help transform policies for schemes such as Work and Income and ACC.

“There’s no consistency in how that’s working at the moment.”

Crossan said it also prompted conversation on what strategies were needed to ensure the individual as well as those such as family or employers were supported.

She was worried that a new government would treat Long Covid like a political football and people would not get the support they needed.

“I’d want to hear pretty quickly from whoever the new Minister of Health is that they are acknowledging that it exists, acknowledging that it’s something that needs to be considered and interested in looking at the research.

“The reality is, if this is the trajectory that we’re on, which it feels like we are, we’re going to end up with an enormous percentage of our population at some degree of suffering from Long Covid at any one time.”

 


◆Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution【bioRxiv　2023年11月2日】

Abstract

Measures to control the COVID-19 pandemic such as antiviral therapy and vaccination have been challenged by ongoing virus evolution under antiviral and immune pressures. Understanding viral evolutionary dynamics is crucial for responding to SARS-CoV-2, and preparing for the next pandemic, by informing prediction of virus adaptation, public health strategies, and design of broadly effective therapies. Whole-genome sequencing (WGS) of SARS-CoV-2 during the pandemic enabled fine-grained studies of virus evolution in the human population. Serial passaging in vitro offers a controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage.

Nine virus lineages, including four “variants of concern” and three former “variants under investigation” as designated by the World Health Organisation, were chosen to investigate intra- and inter-lineage evolution through long-term serial passaging in Vero E6 cells. Viruses were sampled over at least 33 passages (range 33-100) and analysed using WGS to examine evolutionary dynamics and identify key mutations with implications for virus fitness, transmissibility, and immune evasion. All passages continued to replicate in culture, despite regular accumulation of mutations. There was evidence of convergent acquisition of mutations both across passage lines and compared with contemporaneous SARS CoV-2 clinical sequences from population studies. Some of these convergent mutations are hypothesised to be important in proliferation of SARS-CoV-2 lineages, such as by evading host immune responses (e.g. S:A67V, S:H655Y). Given these mutations arose in vitro, in the absence of a multicellular host immune response, this suggests virus genome mutation resulted from stochastic events, rather than immune-driven mutation. There was a regular gain and loss of low-frequency variants during serial passaging, but some became fixed in subsequent multiple passages, suggesting either a benefit of the mutation in vitro, or at least a lack of deleterious effect. Our findings reveal valuable insights into the evolution of SARS-CoV-2 by quantitatively investigating evolutionary dynamics of the virus over the greatest number of serial passages to date. Knowledge of these evolutionary trends will be useful for public health and the development of antiviral and vaccine measures to reduce the effects of SARS CoV-2 infection on the human population.

Introduction

The COVID-19 pandemic saw whole-genome sequencing (WGS) embraced on an unprecedented scale, with nearly 100 countries worldwide possessing SARS-CoV-2 WGS capability and contributing to publicly available sequencing repositories. Consequently, the number of high quality full-genome sequences for SARS-CoV-2 (>14,000,000 as of July 2023) far exceeds that of any other pathogen. The availability of these sequencing data have allowed the population-scale evolution of SARS-CoV-2 to be characterised with fine-grained detail, facilitating real-time monitoring of the spread of SARS-CoV-2, identification of new viral lineages, and have provided crucial insights into virus evolution. For example, the rise and fall of different SARS-CoV-2 lineages has been charted, with attempts to link the presence of key mutations with lineage success in promulgation through the human population. This wealth of genomic data has been vital in guiding public health responses, vaccine design, and antiviral treatments.

Global sequencing efforts have revealed that SARS-CoV-2 has continued to accumulate mutations throughout its genome since first emerging globally in 2020. The rate of mutation accumulation within SARS-CoV-2 (∼1 × 10-6 to 2 × 10-6 mutations per nucleotide per replication cycle) is typical of betacoronaviruses, but below the rate typical in other RNA viruses that lack proofreading mechanisms. Charting the changes accruing in the SARS-CoV-2 genome in real time has allowed quantitative inference of evolutionary processes, such as the diversification of the virus into distinct phenotypes with different transmissibility, disease severity, and immune evasion properties. Retrospective consideration can divide the COVID-19 pandemic into several ‘eras’: the initial phase of the pandemic characterised by apparently limited evolution of the virus, the sudden emergence of the highly divergent virus lineages with altered phenotypes (variants of concern, VOCs), and periods of gradual evolution within VOC lineages. Determining the evolutionary forces responsible for each of these eras is key to understanding how the pandemic has progressed over time, how it will continue to progress as SARS-CoV-2 shifts towards being an endemic virus, and how future pandemics might unfold.

Analysis of the changes that have occurred in SARS-CoV-2 genomes from the global clinical population suggests the predominant driver of evolution in SARS-CoV-2 has been the accumulation of mutations resulting in increased transmissibility. Increased transmissibility is a multifaceted trait resulting from a given virus having an increased ability to survive within an infected individual, shed from an infected individual, establish within a new individual, or some combination of each of these abilities. These are all influenced by virus evading the host immune response. A range of ‘key mutations’ that are partially and additively responsible for each of these components of transmissibility have been identified. For example, several mutations in the Spike region have been linked to enhanced receptor binding, such as D614G, identified early in the pandemic, and N501Y, which was identified in several VOCs. These conclusions predominantly based on clinical observations, albeit with further laboratory-based exploration, are valuable for understanding how the pandemic has unfolded and will continue to unfold.

Whilst genomic data derived from routine genomic sequencing for clinical or surveillance purposes (henceforth referred to as the “clinical population” of SARS-CoV-2) has enhanced understanding the evolution of SARS-CoV-2, there are inherent limitations in relying solely on this information. The availability of WGS data is influenced by differential sequencing efforts between countries, especially when routine WGS is difficult to achieve in low- and middle-income countries, or when data sharing in online repositories is not consistent among jurisdictions. Additionally, the gain or loss of mutations in these populations is affected by multiple uncontrolled processes including natural selection, genetic drift, host immunity, and population dynamics. Understanding the relative impact of each process is difficult in such an uncontrolled environment. Consequently, it is challenging to understand the adaptation of SARS-CoV-2 to specific selective pressures, or to predict the potential evolutionary pathways, when relying solely on the clinical population.

Serial passaging in vitro provides complementary insights into the ongoing evolution of viruses. In these experiments, the virus is passaged through successive generations within a cell line, allowing study of virus evolution in a controlled setting, as mutations accumulate over time during the course of passaging. Most commonly, in vitro serial passaging is conducted to develop virus stocks and assess therapeutics, or to assess virus attenuation for vaccine development. Serial passaging can also be used to study the evolutionary trajectory of viruses over long term experiments, with strictly controlled time periods. These experiments can determine the speed at which a virus develops resistance to antiviral therapies, or to understand how the virus evolves over longer periods in the absence of selective constraints including immune pressure.

Few studies have investigated the evolutionary dynamics of SARS-CoV-2 over time in vitro. Based on limited passaging of ancestral lineages (<15 passages), it was reported that SARS-CoV-2 accumulates mutations readily in vitro, especially when passaged in Vero E6 cells, with an estimated in vitro spontaneous mutation rate of 1.3 × 10-6 ± 0.2 × 10-6 per-base per-infection cycle. There is evidence for the convergent acquisition of mutations among samples taken through serial passage, such as through accumulation of mutations associated with Vero E6-cultured samples, or associated with the global clinical population of SARS-CoV-2. However, these studies explicitly focusing on tracking the evolution of SARS-CoV-2 in vitro generally studied a relatively small number of passages (e.g. <10), over a short time, and relatively few SARS-CoV-2 lineages. The greatest number of lineages published to date is 15 passages with two lineages from early in the pandemic. Further in vitro serial passaging studies of SARS-CoV-2 are needed to: i) more closely approach the multiple passages occurring the human population, ii) assess sites of mutation fixation, iii) use this assessment to determine potential antiviral and vaccine resistance sites developing without antiviral or vaccine pressure, and iv) inform therapeutic and vaccine research. In this study, we compared the accumulation of mutations in vitro in 11 different passaged viruses, corresponding to nine unique Pango lineages, throughout long-term serial passaging (33-100 passages per passaged virus line). The evolutionary dynamics of these passage lines was determined by characterising the mutations that accumulated, both in terms of their number and potential functional consequences. Additionally, we assessed mutations for evidence of convergence across passage lines and/or with key mutations from the global clinical population of SARS-CoV-2.

 


◆Injury mechanism of COVID-19–induced cardiac complications【Cardiology Plus　2023年6月23日】

Abstract

Heart dysfunction is one of the most life-threatening organ dysfunctions caused by coronavirus disease 2019 (COVID-19). Myocardial or cardiovascular damage is the most common extrapulmonary organ complication in critically ill patients. Understanding the pathogenesis and pathological characteristics of myocardial and vascular injury is important for improving clinical diagnosis and treatment approach. Herein, the mechanism of direct damage caused by severe acute respiratory syndrome coronavirus 2 to the heart and secondary damage caused by virus-driven inflammation was reviewed. The pathological mechanism of ischemia and hypoxia due to microthrombosis and inflammatory injury as well as the injury mechanism of tissue inflammation and single myocardial cell necrosis triggered by the viral infection of pericytes or macrophages, hypoxia, and energy metabolism disorders were described. The latter can provide a novel diagnosis, treatment, and investigation strategy for heart dysfunctions caused by COVID-19 or the Omicron variant.

INTRODUCTION

There have been at least six million deaths led by the novel coronavirus disease 2019 (COVID-19) on a global scale. Heart complications are among the most severe manifestations in patients with COVID-19. As the incidence of myocarditis and cardiovascular diseases due to COVID-19 continuously increases, the effect of COVID-19 on heart tissues has garnered considerable attention. The cardiovascular system affected by COVID-19 has complications including myocardial injury, myocarditis, myocardial infarction, heart failure, arrhythmia, and venous thromboembolic events. In view of the essential role of heart disease symptoms in patients with COVID-19, it is essential to identify the cardiac injury mechanism of COVID-19. Previously, several mechanisms have been postulated to explain COVID-19–associated cardiac injury, including direct myocardial injury mediated via angiotensin converting enzyme 2 (ACE2), immune dysregulation mediated by cytokine storm, hypoxia from imbalance in oxygen supply, cardiotoxicity of antiviral drugs as well as demand mediated by ischemia. Descriptions regarding the pathological presentation of COVID-19 cardiac injury was predominantly obtained from autopsy-based literature. Cardiac abnormalities have been discovered in the gross pathology or histologic findings in approximately all of the cases. In these cases, the average age of the deceased was 69 years, and male cases account for more than half of all cases.

 


◆Association of SARS-CoV-2 Infection during Early Weeks of Gestation with Situs Inversus【The NEW ENGLAND JOURNAL of MEDICINE　2023年11月2日】

Situs inversus, including situs inversus totalis (with dextrocardia) and partial situs inversus (with levocardia), is a rare congenital condition in which visceral organization is inverted as compared with normal organ development. We noted a striking increase in the number of cases of fetal situs inversus that were diagnosed by means of ultrasonography at our hospital several months after the “zero-Covid” policies in China were lifted.

We determined the incidence of fetal situs inversus from January 2014 through July 2023 using clinical data from two obstetrical centers in different regions of China. During the first 7 months of 2023, the incidence of situs inversus (diagnosed by means of routine ultrasonography at a gestational age of approximately 20 to 24 weeks, with no change having been made in the diagnostic protocol or physician training) at these centers was over four times as high as the mean annual incidence from 2014 through 2022 (Figure 1 and Fig. S1 and Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org); the incidence peaked in April 2023 and remained elevated through June 2023. Overall, 56 cases of situs inversus were identified from January 2023 through July 2023 (52 cases of situs inversus totalis and 4 cases of partial situs inversus). The increase followed the surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections that occurred after the zero-Covid policies were discontinued; this surge, which ultimately was estimated to affect approximately 82% of the population in China, began in early December 2022, peaked around December 20, 2022, and ended in early February 2023. Although no conclusions can be made regarding causality, our observations suggest a possible relationship between SARS-CoV-2 infection and fetal situs inversus that warrants further study.

Congenital situs inversus has been linked to aberrant morphogen distribution and cilia dysfunction of the left–right organizer in visceral lateralization during the early weeks of gestation. Although vertical transmission of SARS-CoV-2 is debated, fetal infection early in gestation could hypothetically affect visceral lateralization; alternatively, SARS-CoV-2–mediated maternal inflammatory responses might indirectly affect left–right organizer function and impair visceral lateralization. Further analysis is necessary to verify that genetic abnormalities in primary ciliary dyskinesia–related genes that may not have been detected during prenatal genetic screening did not contribute to the incidence of these cases and to assess the potential contribution of environmental factors. It is notable that situs inversus diagnoses remained extremely rare despite the increase in incidence at our centers after the SARS-CoV-2 surge.

 


◆First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody【Science Advances　2023年10月12日】

Abstract

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell–trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

INTRODUCTION

Understanding the adaptive immune response to viral infections and subsequent immunological memory is critical for the development of vaccines and therapeutic options. Studying the immune response in humans has been conventionally focused on peripheral blood assays, particularly in longitudinal studies, due to complexity and invasive nature of tissue sampling approaches. However, most of the immune cells involved in the adaptive immune response and immunological memory reside and function in tissue, particularly in lymphoid organs such as the bone marrow, spleen, tonsils, and lymph nodes. CD8+ T cells are one of the key players in cell-mediated immune response against viral infections, and there has been a growing interest in studying the critical role of CD8+ T cell trafficking and preferential residence of CD8+ memory T cells in certain niches, such as the bone marrow, in immunological memory.

The recent pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emphasized the need to better understand the role of adaptive immunity in viral infections, and there has been particular interest in the role of T cell response to the coronavirus disease 2019 (COVID-19). Immunological memory to SARS-CoV-2 infection has been extensively characterized in the blood. In particular, SARS-CoV-2–specific CD8+ memory T cell response appears to persist for at least 8 months in the blood, with a declining trend observed between 1 and 8 months after infection. Furthermore, examination of SARS-CoV-2 seropositive organ donors has shown SARS-CoV-2–specific CD8+ T cell memory in the bone marrow, spleen, lung, and lymph nodes for up to 6 months after infection.

A noninvasive method capable of quantifying T cell density and trafficking rates in the tissue at a system level for the whole body could enable longitudinal studies in patients with viral infections and in the healthy populations, leading to better understanding of the adaptive immune response and immunological memory. The case for developing such a method for researching COVID-19 infection would include the acute and recovery phases, pre-existing immunity, asymptomatic response, and herd immunity. These could be extended to studies of susceptibility to COVID-19 in association with age, genetic factors, gender, children, and obesity. Being able to noninvasively study T cell involvement in peripheral effects, long COVID, vaccine efficacy, and therapeutic interventions would also suggest potentially fruitful areas for whole-body COVID-19 research.

As a proof of concept for staging such a transformative research strategy, a highly sensitive quantitative in vivo imaging methodology targeting human CD8+ cells is described, with a particular interest toward studying the immunobiology of CD8+ T cells as the major population of human CD8+ cells. For this, the recently developed imaging probe 89Zr-Df-Crefmirlimab, also known as 89Zr-Df-IAB22M2C, is used with positron emission tomography (PET). IAB22M2C is a biologically inert 80-kDa minibody with high affinity to human CD8 and has accelerated serum clearance compared to full-sized antibodies, making it particularly favorable for in vivo imaging. IAB22M2C conjugated to the chelator desferrioxamine (Df) and radiolabeled with Zirconium-89 (89Zr) has been successfully used in a number of preclinical and clinical trials with a focus on cancer immunotherapy applications. With a long radioactive half-life of 78.4 hours, 89Zr allows the tracer’s biodistribution to be followed for several days post-injection (p.i.). However, because of its long half-life, radiation dose concerns have prevented wider application of 89Zr-immunoPET in non–life-threatening disease and healthy populations. The advent of total-body PET scanners covering all or much of the body, which offer a radiation detection sensitivity increase of one to two orders of magnitude compared to conventional PET scanners, enables high signal-to-noise ratio imaging of 89Zr-based radiotracers at substantially lower injected doses in addition to capturing kinetics across all the organs and tissues of interest. This enables complete characterization of the pharmacokinetics of these immunological PET tracers across a wide range of applications. Total-body PET is currently the only available technology that allows noninvasive in vivo measurements of T cell distribution and kinetics inside all tissues in human subjects, with acceptable radiation dose burden. In this work, low (<20 MBq) doses of 89Zr-Df-Crefmirlimab tracer were used with the 194-cm-long uEXPLORER total-body PET scanner to study the biodistribution and kinetics of CD8+ cells in COVID-19 convalescent patients and in healthy controls.

 


◆Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity【Frontiers in Immunology　2023年10月10日】

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).

Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge.

Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts.

Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

Introduction

A significant proportion of patients develops long-lasting symptoms after coronavirus disease 2019 (COVID-19). Different terms have been used to describe this condition, such as long COVID, post-acute COVID-19 syndrome, post-acute sequelae of COVID-19, long-haulers, or post COVID-19 condition. In the current report, we will use the term long COVID, consistent with most literature and the most commonly used terminology amongst patients. Long COVID represents a broad spectrum of ─ often disabling ─ symptoms. Frequently reported symptoms of long COVID are fatigue, impaired fitness, dyspnea, and neuropsychiatric complaints. Numerous studies showed the presence of these symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with evidence of persistence even two years after the infection. As patients with long COVID differ substantially regarding symptoms, severity, and recovery profile, attempts have been made to discern different clinical phenotypes of long COVID without reaching consensus to date.

Disabling fatigue is one of the most prominent and debilitating symptoms of long COVID. Studies have reported that up to 41% to 60% of patients who had been hospitalized for COVID-19 still suffer from fatigue one year post-discharge, without evident improvement beyond 6 months and negatively impacting quality of life. Fatigue may coexist with other symptoms; studies showed that fatigue is associated with neuropsychiatric symptoms, such as depression, in patients one year after hospitalization for COVID-19. We have extensively analyzed the underlying immunopathogenic mechanisms of mood disorders in previous studies and similar mechanisms might (partially) underlie the prolonged fatigue in long COVID. This problem thus requires in-depth evaluation regarding its pathogenesis, facilitating future interventions.

The prolonged fatigue state after acute COVID-19 shows clinical similarities with other post-infectious fatigue syndromes, such as that after Coxiella burnetii (Q fever) and Epstein-Barr virus (infectious mononucleosis) infection, and also shows similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The latter is characterized by a range of debilitating symptoms, including fatigue, post-exertional malaise (a worsening of symptoms after minimal physical or mental exertion), sleep disturbances, and neurocognitive impairments. Ongoing immune activation, reflected by for instance increased serum cytokine levels and increased circulating CD8+ T-lymphocyte numbers, has been described in both post-infectious fatigue conditions and ME/CFS and is thought to play a role in the pathophysiology of these conditions. Given the clinical similarities with post-infectious fatigue syndromes and ME/CFS, a similar immune activation may be involved in long COVID.

To date, several studies have identified persistent inflammatory monocyte and T- and B-lymphocyte abnormalities among patients in the convalescent phase of COVID-19. Few studies assessed the association between specific symptoms of long COVID with immunological characteristics. However, a comprehensive and in-depth clinical and immunologic assessment focusing on fatigue, one of the most frequently reported symptom of long COVID, is lacking.

This study aimed to compare clinical and immune profiles of long COVID patients with and without fatigue, as well as with age- and sex-matched healthy individuals. We hypothesized that 1. long COVID patients have a distinct immune profile compared to healthy controls and 2. Long COVID with fatigue would exhibit a more severe and/or different clinical and immune profile than those without fatigue, and would show an immune profile comparable to patients with ME/CFS and mood disorders. We performed an immune assessment between 3-6 months after hospital discharge while clinical symptoms, evaluated with patient-reported outcome measures (PROMs), were longitudinally assessed for up to one-year post-discharge. We determined the expression of various sets of inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes. These assays were selected because we have previously shown that these assays revealed abnormalities in immune function in patients with various mental and somatic disorders and ME/CFS (unpublished data).

 


◆Exploring COVID-19 conspiracy theories: education, religiosity, trust in scientists, and political orientation in 26 European countries【NIH　2023年10月23日】

Abstract

The COVID-19 virus disseminated globally at an accelerated pace, culminating in a worldwide pandemic; it engendered a proliferation of spurious information and a plethora of misinformation and conspiracy theories (CTs). While many factors contributing to the propensity for embracing conspiracy ideation have been delineated, the foremost determinant influencing individuals’ proclivity towards CT endorsement appears to be their level of educational attainment. This research aimed to assess the moderating effect of religiosity, trust in scientists, and political orientation on the impact of education level on people’s belief in COVID-19-related CTs in Europe by considering both individual-level and country-level contextual covariates of CT. We analysed data from the newest European Social Survey (ESS10) round conducted between September 2020 and September 2022 in 26 countries. We found religiosity weakens, and trust in scientists strengthens the effect of education, while the impact of political orientation is not straightforward. The result also demonstrates a significant negative correlation between the aggregate country-level data of the respondents supporting CTs and the level of vaccination and cumulative excess deaths in Europe. We concluded with a recommendation that planning effective public health strategies and campaigns are insufficient when based solely on people’s education, as individuals’ beliefs moderate the effect of education.