SARS-CoV-2 と COVID-19 に関するメモ・備忘録
2020年以降、心臓腫瘍の件数が1.5倍に増加しており、11件中10件の腫瘍細胞、内皮細胞、およびマクロファージでコロナウイルスのスパイクプロテインが検出されたという研究。特に粘液腫の増加が顕著だった。https://t.co/0fQQa5T4t4 #mdpilife @Life_MDPIより
— Angama (@Angama_Market) October 24, 2023
見つかったウイルスの遺伝子解析も進めてほしいですね。
— Angama (@Angama_Market) October 25, 2023
最近査読が物凄く通りにくいそうですよ。
— Angama (@Angama_Market) October 26, 2023
心臓の腫瘍なんてめっちゃ珍しいはずなのに、コロナ以降で1.5倍に増加。 https://t.co/HXebzSzkCg
— چیفومی (@chifumi_k) October 24, 2023
その腫瘍の中からもスパイクプロテインが見つかったというのがインパクトあります。
— Angama (@Angama_Market) October 25, 2023
腫瘍細胞の中でコロナウイルスのスパイクプロテインが見つかるというのは、明確に発がん性を示唆しているようですね。
— Angama (@Angama_Market) October 24, 2023
「スパイクタンパク質は、ACE2受容体に結合し、細胞のミトコンドリアに損傷を与え、微小血栓症と内皮炎を引き起こします。」
ミトコンドリアは細胞が異常化した場合、それを制御する役割がありますが、ミトコンドリアの損傷すると、それが機能せずに癌細胞になるのを許してしまいます 。
— 🇺🇦規制明け絶対民主法治国家維持🇺🇦 (@B6VECcNetVjoam7) October 25, 2023
ミトファジーが抑制されますね。
— Angama (@Angama_Market) October 25, 2023
◆High Risk of Heart Tumors after COVID-19【MDPI 2023年10月20日】
Abstract
An emergence of evidence suggests that severe COVID-19 is associated with an increased risk of developing breast and gastrointestinal cancers. The aim of this research was to assess the risk of heart tumors development in patients who have had COVID-19. Methods: A comparative analysis of 173 heart tumors was conducted between 2016 and 2023. Immunohistochemical examination with antibodies against spike SARS-CoV-2 was performed on 21 heart tumors: 10 myxomas operated before 2020 (the control group), four cardiac myxomas, one proliferating myxoma, three papillary fibroelastomas, two myxofibrosarcomas, one chondrosarcoma resected in 2022–2023. Immunohistochemical analysis with antibodies against CD34 and CD68 was also conducted on the same 11 Post-COVID period heart tumors. Immunofluorescent examination with a cocktail of antibodies against spike SARS-CoV-2/CD34 and spike SARS-CoV-2/CD68 was performed in 2 cases out of 11 (proliferating myxoma and classic myxoma). Results: A 1.5-fold increase in the number of heart tumors by 2023 was observed, with a statistically significant increase in the number of myxomas. There was no correlation with vaccination, and no significant differences were found between patients from 2016–2019 and 2021–2023 in terms of gender, age, and cardiac rhythm dis-orders. Morphological examination revealed the expression of spike SARS-CoV-2 in tumor cells, endothelial cells, and macrophages in 10 out of 11 heart tumors. Conclusion: The detection of SARS-CoV-2 persistence in endothelium and macrophages as well as in tumor cells of benign and malignant cardiac neoplasms, the increase in the number of these tumors, especially cardiac myxomas, after the pandemic by 2023 may indicate a trend toward an increased risk of cardiac neoplasms in COVID-19 patients, which re-quires further research on this issue and a search for new evidence.
コロナウイルス長期障害のバイオマーカーには一貫性がないことが多いが、冠動脈形成術後のアテローム性動脈硬化に特徴的なP-セレクチンと、血漿漏出の抑制、血管炎症の抑制などで働くアンジオポエチン-1 (Ang1)が長期障害者には有意に多いことが分かったという研究。https://t.co/adStHNHr6M
— Angama (@Angama_Market) October 26, 2023
◆Validation of ANG-1 and P-SEL as biomarkers of post-COVID-19 conditions using data from the Biobanque québécoise de la COVID-19 (BQC-19)【Clinical Proteomics 2023年10月24日】
Abstract
The quest for understanding and managing the long-term effects of COVID-19, often referred to as Long COVID or post-COVID-19 condition (PCC), remains an active research area. Recent findings highlighted angiopoietin-1 (ANG-1) and p-selectin (P-SEL) as potential diagnostic markers, but validation is essential, given the inconsistency in COVID-19 biomarker studies. Leveraging the biobanque québécoise de la COVID-19 (BQC19) biobank, we analyzed the data of 249 participants. Both ANG-1 and P-SEL levels were significantly higher in patients with PCC participants compared with control subjects at 3 months using the Mann-Whitney U test. We managed to reproduce and validate the findings, emphasizing the importance of collaborative biobanking efforts in enhancing the reproducibility and credibility of Long COVID research outcomes.
剖検された重症COVID-19患者の遺体においてSARS-CoV-2 RNAが冠動脈病変において認められ、複製されていることがわかった。
SARS-CoV-2は血管周囲脂肪組織よりも冠動脈プラーク内のマクロファージに強い指向を示した。
→— Sukuna (@SukunaBikona7) October 26, 2023
培養されたマクロファージと取り出したアテローム性動脈硬化した血管のモデルでSARS-CoV-2は冠動脈イベントの契機となるサイトカイン分泌を伴う強い炎症反応を示した。https://t.co/XDvtLOyvCg
ウイルスが冠動脈病変自体に感染し、そこで炎症を引き起こすことがCOVID-19に伴う冠動脈リスク上昇の→— Sukuna (@SukunaBikona7) October 26, 2023
原因かも、と。
ウイルスRNAの局在を見るときにAIを使っているのは面白い。— Sukuna (@SukunaBikona7) October 26, 2023
◆SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels【nature cardiovascular research 2023年9月28日】
Abstract
Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events. Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.
10/23月 #山口県宇部市下水サーベイランス
⚠️激増。秋冬の波もそろそろの時期だが、来週はどうなるだろうかhttps://t.co/ekiPo6ps9X https://t.co/F5wyIxzM65 pic.twitter.com/wuO4bkfAtF
— Takuro⚓️コロナ情報in全国/神奈川/横浜/川崎/東京/大阪/岐阜/広島/宮崎/愛知/静岡 (@triangle24) October 28, 2023
これはまずい兆候ですね。仙台は減っていないし、札幌は増加に転じていました。いよいよ、「津波から高潮状態」が現実になりそうな勢いです。「ウィズコロナ」の実相を社会全体が理解するのはいつになるのやら。 https://t.co/s3j0dWjsTC
— FORCEPS (@FORCEPS4) October 28, 2023
今回、第10波入り、早くないですか? https://t.co/Kr6m8O26y4
— R連続体 MT Ph.D H.Sc. (@Rrenzokutai) October 28, 2023
今回、第10波入り、早くないですか? https://t.co/Kr6m8O26y4
— R連続体 MT Ph.D H.Sc. (@Rrenzokutai) October 28, 2023
理由は簡単で、感染防御水準を官邸主導の国策でほぼゼロにしたためです。
このため遅延効果が全く働かず、ウイルスの増加圧力が何にも邪魔されずに現れています。
これはペン二郎さんと同じ考えですが、既感染率が100%に接近するので今回で終わりかもしれません。これが最善予測です。→(最悪予測へ)
— Hiroshi Makita Ph.D. 誰が日本のコロナ禍を悪化させたのか?扶桑社8/18発売中 (@BB45_Colorado) October 28, 2023
→以下はあくまで最悪予測です。可能性の一つです。
初接触抗原が大部分mRNAワクチンかつ世界一の瀕回接種・世界最高の接種率と言う日本の特殊性がImmune Imprintingを起していればもはやワクチンも感染獲得抗体も半永久的に効かず、夏季Surgeと秋季・冬季Surgeは、今後も大規模に繰り返されます。
— Hiroshi Makita Ph.D. 誰が日本のコロナ禍を悪化させたのか?扶桑社8/18発売中 (@BB45_Colorado) October 28, 2023
今季Surgeについては、過去最大規模のSurgeとなりかつ、季節効果で9th Surgeより毒性が高くなると考えています。
また、EG.5.xに続くドミナント候補株がGK.1.1x, HK.3.x, BA.2.86x, (XBC)と3+1ありますので、2~4波となる見込です。
GK.1.1x, HK.3xが予想外に免疫回避強化株であるのも懸念材料です。
— Hiroshi Makita Ph.D. 誰が日本のコロナ禍を悪化させたのか?扶桑社8/18発売中 (@BB45_Colorado) October 28, 2023
無症状の赤ちゃん、実は重症の免疫不全症だった…新生児検査で初診断、移植受け無事退院 鹿児島大学病院|南日本新聞|2023.10.28https://t.co/pLiIZucBNE
— はな❄️NO WAR (@aoihana1213) October 28, 2023
鹿児島市の鹿児島大学病院は27日、生まれてすぐに赤ちゃんが受けるスクリーニング検査で、無症状の男児を重症の免疫不全症と診断したと発表した。男児は造血幹細胞移植を受け経過は良好、同日退院した。
— はな❄️NO WAR (@aoihana1213) October 28, 2023
先天的な病気を見つけるための「新生児マススクリーニング検査」の対象に県内では2022年8月から同症が追加されており、検査で見つかったのは初めて。
同院小児科の西川拓朗准教授によると、男児の病気は重症複合免疫不全症(SCID)。
— はな❄️NO WAR (@aoihana1213) October 28, 2023
生まれつきTリンパ球などの免疫機能が働かないため、ささいな感染症でも重症化しやすい。診断前にロタウイルスワクチンを接種すると死亡するケースもある。根治には造血幹細胞移植が有効。
— はな❄️NO WAR (@aoihana1213) October 28, 2023
マススクリーニングは、現在県内で20疾患が公費負担。SCIDなどが追加でできる「拡大検査」は、1万円程度が自己負担となる。ほとんどの産婦人科で受けることができる。
— はな❄️NO WAR (@aoihana1213) October 28, 2023
男児は、肝付町の島田蓮仁ちゃん(7カ月)。母・真実さん(34)は「検査で救える命がある。うちの子は大丈夫と思わずに多くの人に知ってもらえたら」と話した。
西川准教授は「鹿児島は検査から治療までできる環境にある。赤ちゃんの命を守るためにも拡大検査を受けてもらいたい」と呼びかけた
— はな❄️NO WAR (@aoihana1213) October 28, 2023
抗コロナウイルス薬モルヌピラビルが、ウイルスの進化速度を高める可能性がある遺伝子に多数の変異を誘発し、進化を加速させていることが分かったという記事。
Anti-COVID drug accelerates viral evolution https://t.co/BPMr1b5Byf
— Angama (@Angama_Market) October 25, 2023
母集団がもう桁違いなので、確率演算も他の病原体とは比較にならないほど速いのだと思います。
— Angama (@Angama_Market) October 26, 2023
モルヌピラビルのUSでの承認時にも議論に挙がってましたね。
下は2年前の記事です。
モルヌピラビルは新型コロナには30%あるかないかの効果なので、残りの70%はモルヌピラビルをすり抜け、生き残ることを意味しているし、作用機序から言っても変異を助長する薬ですね。https://t.co/Y5rIRj15ef— 🇺🇦規制明け絶対民主法治国家維持🇺🇦 (@B6VECcNetVjoam7) October 25, 2023
コロナウイルスは動脈細胞以上にマクロファージや泡沫細胞に感染することが分かったという研究。コレステロールを多く含む泡沫細胞は最も感染しやすく、アテローム性動脈硬化プラーク内でウイルスの貯蔵庫に。感染した細胞はサイトカインを放出しさらにプラークを拡大していたhttps://t.co/u6AdYFg1zO
— Angama (@Angama_Market) October 20, 2023
コロナウイルス感染においてはマクロファージはほとんど足を引っ張る作用ばかりです。
— Angama (@Angama_Market) October 24, 2023
だから肥満が重症化のリスクを上げるんだな。 https://t.co/MrWGpGDAoU
— چیفومی (@chifumi_k) October 20, 2023
これは本当にヤバイ。
今までおとなしくしていた「生活習慣病→動脈硬化→血管閉塞→臓器の壊死(脳梗塞、心筋梗塞、閉塞性動脈硬化症など)」の爆弾が、新型コロナ感染によって勝手に起動し始めるようなもの。糖尿病の発病リスクも感染によって高まることが既にわかっているし。特に中高年は危険。 https://t.co/bCNQXXQaOg— 「戦い続ける」ザオラルさん【JCP】🌈 (@OneMoreChance99) October 20, 2023
◆SARS-CoV-2 infects coronary arteries, increases plaque inflammation【NIH 2023年9月28日】
SARS-CoV-2, the virus that causes COVID-19, can directly infect the arteries of the heart and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke, according to a study funded by the National Institutes of Health. The findings(link is external), published in the journal Nature Cardiovascular Research, may help explain why certain people who get COVID-19 have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications.
In the study, researchers focused on older people with fatty buildup, known as atherosclerotic plaque, who died from COVID-19. However, because the researchers found the virus infects and replicates in the arteries no matter the levels of plaque, the findings could have broader implications for anybody who gets COVID-19.
“Since the early days of the pandemic, we have known that people who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection,” said Michelle Olive, Ph.D., acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.”
Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches the cells, the body’s immune system sends in white blood cells known as macrophages to help clear the virus. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with cholesterol, they morph into a specialized type of cell called foam cells.
The researchers thought that if SARS-CoV-2 could directly infect arterial cells, the macrophages that normally are turned loose might increase inflammation in the existing plaque, explained Chiara Giannarelli, M.D., Ph.D., associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine and senior author on the study. To test their theory, Giannarelli and her team took tissue from the coronary arteries and plaque of people who had died from COVID-19 and confirmed the virus was in those tissues. Then they took arterial and plaque cells – including macrophages and foam cells – from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues.
Additionally, the researchers found that when they compared the infection rates of SARS-CoV-2, they showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID-19.
The researchers then turned their attention to the inflammation they predicted might occur in the plaque after infecting it with the virus. They quickly documented the release of molecules, known as cytokines, that are known to increase inflammation and promote the formation of even more plaque. The cytokines were released by infected macrophages and foam cells. The researchers said this may help explain why people who have underlying plaque buildup and then get COVID-19 may have cardiovascular complications long after getting the infection.
“This study is incredibly important as it adds to the larger body of work to better understand COVID-19,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.”
Though the findings conclusively show that SARS-CoV-2 can infect and replicate in the macrophages of plaques and arterial cells, they are only relevant to the original strains of SARS-CoV-2 that circulated in New York City between May 2020 and May 2021. The study was conducted in a small cohort of older individuals, all of whom had atherosclerosis and other medical conditions; therefore, the results cannot be generalized to younger, healthy individuals.
This work was funded by the NIH/NHLBI grants 1R01HL165258, R01HL153712, R35HL135799 and R01HL084312. NIAID and NIDDK also provided funding.
コロナウイルス長期障害と繰り返される感染は、予見可能な範囲の未来において国家的問題だが、既に大きく広がっていて全貌すら不明。唯一確実な予防手段はコロナウイルスに感染しないことしかない、というオーストラリア議会の報告書。https://t.co/A2ofSkTkLt
— Angama (@Angama_Market) October 26, 2023
コロナウイルス感染に伴い、急性横断性脊髄炎 (ATM) と縦方向広範囲横断性脊髄炎 (LETM)が発生することがあるという研究。患者は発熱、嘔吐などで急患。 陽性反応数日後、両手足の筋力低下、尿閉、嚥下障害を発症。高用量のステロイドと血漿交換の結果、症状が僅かに改善したhttps://t.co/nvKmdGm6OC
— Angama (@Angama_Market) October 26, 2023
少し前に投稿したプリオン病とされていた症状にも似ている気がします。
— Angama (@Angama_Market) October 27, 2023
◆A Case of Longitudinally Extensive Transverse Myelitis Following COVID-19 Infection【Cureus 2023年10月24日】
Abstract
One of the rare complications following acute COVID-19 infection is acute transverse myelitis (ATM). With only a few cases of ATM reported in the literature, an addition of longitudinally extensive transverse myelitis (LETM) diagnosed in our patient would underscore the complexity and diversity of neurological manifestations associated with this viral illness. A 54-year-old patient presented to the emergency department with fever, shortness of breath, nausea and vomiting. The patient’s nasopharyngeal swab for COVID-19 polymerase chain reaction (PCR) resulted positive. Few days later, the patient developed bilateral upper, lower extremities weakness, back pain, urinary retention and dysphagia. Subsequently, the clinical presentation, MRI, cerebrospinal fluid (CSF) and laboratory findings pointed toward LETM as a complication of COVID-19 infection over other differentials. The aggressiveness of this disease necessitated high-dose steroids and plasmapheresis, pain control medication and rehabilitation which led to a slight improvement in the neurological symptoms at the time of discharge to the rehabilitation facility.
コロナウイルスのスパイクプロテインの変異速度は、HA型インフルエンザの2倍以上、季節性の普通のコロナウイルスの7倍から10倍以上速く、他のエンデミックウイルスよりも極めて速いペースで変異していることがわかったという研究。https://t.co/HO32skgUVj
— Angama (@Angama_Market) October 27, 2023
少し検索したら、2021年位まで、コロナウイルスの変異速度はインフルエンザの50%程度、という言説が広く出回っていたようです。母数が増えると変異が加速するという要素は完全に度外視していたようですね。
— Angama (@Angama_Market) October 29, 2023
日本はコロナウイルスの研究で世界を牽引してるんですが、ほとんど全て英語で日本以外に発信されています。
— Angama (@Angama_Market) October 29, 2023
◆An atlas of continuous adaptive evolution in endemic human viruses【Cell Host & Microbe 2023年10月24日】
Highlights
- Ongoing adaptive evolution in human endemic viruses is largely in surface proteins
- Immune evasion drives continuous adaptive evolution in many endemic human viruses
- Antigenic evolution occurs in several viral families
- SARS-CoV-2 is accumulating protein-coding changes faster than other endemic viruses
Summary
Through antigenic evolution, viruses such as seasonal influenza evade recognition by neutralizing antibodies. This means that a person with antibodies well tuned to an initial infection will not be protected against the same virus years later and that vaccine-mediated protection will decay. To expand our understanding of which endemic human viruses evolve in this fashion, we assess adaptive evolution across the genome of 28 endemic viruses spanning a wide range of viral families and transmission modes. Surface proteins consistently show the highest rates of adaptation, and ten viruses in this panel are estimated to undergo antigenic evolution to selectively fix mutations that enable the escape of prior immunity. Thus, antibody evasion is not an uncommon evolutionary strategy among human viruses, and monitoring this evolution will inform future vaccine efforts. Additionally, by comparing overall amino acid substitution rates, we show that SARS-CoV-2 is accumulating protein-coding changes at substantially faster rates than endemic viruses.
Graphical abstract