SARS-CoV-2 と COVID-19 に関する備忘録 Vol.12――4週間に2回などと頻繁に再感染する感染症がCovid-19以外にある？…etc.

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録


◆The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research【Cambridge University Press　2023年10月13日】

Abstract

Objective:

We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) among fully vaccinated individuals.

Design:

Systematic literature review/meta-analysis.

Methods:

We searched PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to June 2, 2023, for studies evaluating the COVID-19 vaccine effectiveness (VE) against post-COVID conditions among fully vaccinated individuals who received two doses of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present four or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% confidence interval) for post-COVID conditions between fully vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% x (1-DOR).

Results:

Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR for post-COVID conditions among fully vaccinated individuals was 0.680 (95% CI: 0.523–0.885) with an estimated VE of 32.0% (11.5%–47.7%). Vaccine effectiveness was 36.9% (23.1%–48.2%) among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% (64.7%–72.2%) among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection.

Conclusion:

Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.

Background

In the last three years, extensive research has demonstrated the safety and efficacy of COVID-19 (Coronavirus Disease 2019) vaccines. These vaccines have played a critical role in reducing mortality and hospitalization rates. Furthermore, studies have confirmed the value of additional COVID-19 vaccine doses in sustaining immunization effectiveness and guarding against emerging variants. However, post-COVID conditions, commonly known as long COVID, have become a significant concern as growing evidence suggests that a substantial number of individuals continue to experience persistent symptoms and complications long after the acute phase of the illness.

The Centers for Disease Control and Prevention (CDC) defines post-COVID conditions as a vast range of ongoing health problems (e.g., cardiovascular, respiratory, and neuropsychiatric symptoms) that can last for more than 4 weeks after an individual has been infected by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) virus. These conditions can significantly impact individuals’ quality of life, and daily functioning, and pose a considerable burden on the healthcare system. As of January 2023, 28% of individuals who had a previous COVID-19 infection experienced post-COVID conditions. A systematic review published previously demonstrated that receiving at least one dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccines could prevent the occurrence of long COVID symptoms.

As vaccination campaigns have progressed, the majority of people have received more than one dose of COVID-19 vaccines. However, their effectiveness in preventing post-COVID conditions among fully vaccinated individuals remains an unresolved question. The vaccine effectiveness (VE) against post-COVID symptoms might vary depending on the number of vaccine doses people have received. Hence, our objective was to conduct a literature review on the effectiveness of COVID-19 vaccines, specifically examining the impact of receiving two or more doses of these vaccines in preventing post-COVID conditions. By pooling the findings of published studies, we aimed to provide more accurate estimates of vaccine effectiveness.

 


◆Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study【ScienceDirect　2023年10月2日】

Abstract

As the emergency phase of the COVID-19 pandemic subsides, the long-term health problems caused by SARS-CoV-2 infection are becoming increasingly clear. So-called Long COVID, or post COVID-19 condition, is a debilitating illness that impacts functioning for months and even years after infection. Alongside physical symptoms, Long COVID has a particularly insidious effect on cognition and language. While many studies have documented non-linguistic cognitive impairments in people with Long COVID, what has not been documented to any significant extent is the presence and duration of language difficulties in Long COVID. This study addresses this lack of research by examining the cognitive-linguistic skills of 41 adults with Long COVID. These adults were assessed at two time points using a test protocol of 12 language tasks. This paper describes the findings of the 6-month follow-up study. Results indicate that difficulties in immediate and delayed verbal recall persist long after the onset of COVID symptoms, even as improvements occur in verbal fluency and the informativeness of spoken discourse. It is argued that these difficulties are a significant contributing factor in a lack of work return in these adults. Implications of these findings for the provision of speech-language pathology services to these adults and occupational health policies relating to Long COVID are discussed.

 


◆Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19【Frontiers in Medicine　2023年10月10日】

Introduction: Several efforts have been made to describe the complexity of T cell heterogeneity during the COVID-19 disease; however, there remain gaps in our understanding in terms of the granularity within.

Methods: For this attempt, we performed a single-cell transcriptomic analysis of 33 individuals (4 healthy, 16 COVID-19 positive patients, and 13 COVID-19 recovered individuals).

Results: We found CD8+ T cell-biased lymphopenia in COVID-19 patients compared to healthy and recovered individuals. We also found an optimal Th1/Th2 ratio, indicating an effective immune response during COVID-19. Expansion of activated CD4+ T and NK T was detected in the COVID-19-positive individuals. Surprisingly, we found cellular and metal ion homeostasis pathways enriched in the COVID-19-positive individuals compared to the healthy and recovered in the CD8+ T cell populations (CD8+ TCM and CD8+ TEM) as well as activated CD4+ T cells.

Discussion: In summary, the COVID-19-positive individuals exhibit a dynamic T cell mediated response. This response may have a possible association with the dysregulation of non-canonical pathways, including housekeeping functions in addition to the conventional antiviral immune response mediated by the T cell subpopulation. These findings considerably extend our insights into the heterogeneity of T cell response during and post-SARS-CoV-2 infection.

 


◆Neurologic Effects of SARS-CoV-2 Transmitted among Dogs【CDC　2023年10月13日】

Abstract

SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2–infected dogs, particularly involving blood–brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2–associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.

Since SARS-CoV-2 was first reported in late 2019, infection has been observed primarily in humans; however, animals of various species have also been infected, partially because their angiotensin-converting enzyme 2 (ACE2) receptor is very similar to that of humans. Infected animals show clinical signs similar to those of humans, raising concerns about potential transmission of the virus between humans and animals. SARS-CoV-2 infection in dogs and cats affects the lungs and leads to pathologic changes. However, whether similar pathologic manifestations occur in the brain, as observed in humans, remains unclear.

Close cohabitation of dogs and humans, and their high genetic similarity, has prompted investigations into dogs’ susceptibility to SARS-CoV-2 infection. Wild-type SARS-CoV-2 infection in dogs can induce formation of neutralizing antibodies, and low viral titers in dogs demonstrate seroconversion. Mutant strains of SARS-CoV-2 in dogs cause histopathologic changes in lung tissues and increased expression of muscle damage markers in the blood. ACE2 in dogs can bind to the receptor-binding domain of SARS-CoV-2, implying the possibility of cross-species transmission between humans and dogs. Genetic and epidemiologic studies have reported animal-to-human transmission of SARS-CoV-2.

Reportedly, SARS-CoV-2 can cause neurologic signs and symptoms (e.g., headache, fatigue, and cognitive dysfunction) in human patients. Several cohort studies report strong correlations between SARS-CoV-2 and neurologic signs/symptoms. Furthermore, cortical thickness is reduced in SARS-CoV-2–infected patients, suggesting that SARS-CoV-2 can induce pathologic changes in the brain, which may be linked to the functional deficits noted in those patients. Considering the number of patients infected with SARS-CoV-2, the neurologic signs can lead to a potential wave of neurodegenerative diseases, which could pose an immense burden on society.

The etiology of SARS-CoV-2–induced neuropathologic changes is still elusive. However, clinical and experimental reports suggest that vascular damage and the resultant immune responses in the brain may be a major factor. Magnetic resonance imaging has detected white matter hyperintensities in SARS-CoV-2–infected patients, indicating damage to the blood–brain barrier (BBB) in this region and that potentially demyelinating pathologic changes can be induced. Other studies have revealed signs of neuroinflammatory responses, including activation of microglial cells and astrocytes. Moreover, damage to the brain vasculature and defects in the coagulation system have been demonstrated. The characteristic pathologies observed in human patients (e.g., vascular damage, demyelination, and neuroinflammatory responses) have also been observed in humanized mouse models.

We used a canine transmission model to investigate the susceptibility of dogs to SARS-CoV-2, specifically the Delta variant. The dogs were housed in a Biosafety Level 3 animal facility at Konkuk University Laboratory, Seoul, South Korea, where temperature, humidity, and light were carefully controlled. The study was approved by the Animal Research Center under the supervision of the Institutional Animal Care and Use Committee (accreditation no. KU22065) and the Institutional Biosafety Committee (accreditation no. KUIBC-2022-06) at Konkuk University. The absence of SARS-CoV-2 RNA and SARS-CoV-2 antibodies in dog serum was confirmed.