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【最悪のパターン】
コロナウイルスはACE2受容体を塞いだ状態でもT細胞に感染することが確認。コロナウイルスはACE2受容体を使わずに感染できることが分かったという研究。https://t.co/ZwAE3N2RXm
— Angama (@Angama_Market) March 14, 2022
コロナウイルスはT細胞に直接感染するので、自然感染による免疫の獲得の可能性は完全に存在しないことが明らかに。 https://t.co/C1OwVMraIx
— Angama (@Angama_Market) March 14, 2022
違います。元論文https://t.co/n6x0Yd1UKSによれば、コロナ感染者でリンパ球減少症をきたす(稀です)メカニズムとして、通常はACE2/TMPRSS2を介して細胞に感染するところ、リンパ球にLFA-1を介して感染するようだというのが論文の趣旨でして、免疫獲得が無効かのような結論は導かれません。
— てててああ (@teteteaa) March 15, 2022
◆ACE2-independent infection of T lymphocytes by SARS-CoV-2【Nature 2022年3月11日】
Abstract
SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.
にわかには信じ難いがデータ見るとすごい違い。コロナに感染した人では脳の構造的変化が見られると。認知機能低下は言われていたが具体的な構造上の変化が確認されたのは大きい。具体的には脳の萎縮、特に灰白質。さらに臭覚野関連部位での組織障害が見られたと。 https://t.co/KPl6YNlSdo
— Kazz.MD.Ph.D. (@KazBowen) March 7, 2022
やはり臭覚異常味覚異常と関連あるのかもしれない。ただ全例に出るわけでもなく、確か組織的には臭上皮Neuronには感染していなかったようだったが、違うRootでCNSに感染しているのか?それとも引き起こされる炎症反応が原因?もちろん萎縮しやすい人が感染しやすかった可能性もあるが、
— Kazz.MD.Ph.D. (@KazBowen) March 7, 2022
RootがTypoなの気づいたRouteです。
— Kazz.MD.Ph.D. (@KazBowen) March 7, 2022
50代でも見られているし、感染者群でもそこまでばらつきも大きくないので、コロナが原因だろうね。灰白質だからやはりNeuronの脱落がメインなんだろうね。。ちなみに約4ヶ月半後の検査でもともととってあった画像との比較という方法で見てます
— Kazz.MD.Ph.D. (@KazBowen) March 7, 2022
Figure 追加しとく。オレンジがコロナ。上2つが脳の萎縮を見たもの。高齢者で差が大きい。ただ50代でもそこそこ減ってる。下2つは組織異常の指標。結構な差で驚いてます pic.twitter.com/iTTiyPM2tV
— Kazz.MD.Ph.D. (@KazBowen) March 7, 2022
◆SARS-CoV-2 is associated with changes in brain structure in UK Biobank【Nature 2022年3月8日】
Abstract
There is strong evidence of brain-related abnormalities in COVID-19. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.
【タクシー化】
長期障害に苦しむ29人の患者を調べたところ、検査陽性から平均55日経つにも関わらず血漿と糞尿からウイルスが検出されたという研究。患者の55%が感染時はマイルドな症状だった。https://t.co/rLxYETLETL
— Angama (@Angama_Market) March 4, 2022
◆Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19
【BMC Infectious Diseases 2022年3月3日】
Abstract
Background
There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation.Method
We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use).Results
We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39–67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01).Conclusions
In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.
– ドイツの新たな研究により,多くの小児COVID-19患者が,COVID-19から回復したにもかかわらず,肺の問題や肺の機能障害を発症し持続していることが明らかになりました。これらの小児たちの多くはSARS-CoV-2感染後も後遺症が続いており,現在ではLong COVID Kidsと呼ばれています。https://t.co/NbH4ObSVIX
— fdzaraf (@fdzaraf) February 27, 2022
– この横断的な臨床試験の研究チームは, PCRでSARS-CoV-2感染が確認された5歳~18歳未満の小児および青年において, 非侵襲的,ラベルフリー形態学的,自由呼吸位相分解機能·低磁場·磁気共鳴画像診断(LF-MRI)を使用して肺の変化を確認しました。(https://t.co/5MEuuYFxvi)
— fdzaraf (@fdzaraf) February 27, 2022
– 研究チームは,COVID-19後の小児に持続する肺機能障害について検討しました。過去の研究の多くは,COVIDが小児では成人よりも軽度の症状で発現することを誤って示唆しています。新たに現れた証拠は,小児患者のSARS-CoV-2感染後の急性症状および後遺症の発生率は成人と同程度であることを示しています。
— fdzaraf (@fdzaraf) February 27, 2022
陽性判明から175-462日後に長期障害を患う2人の患者の虫垂と乳がん隣接組織から、コロナウイルスのRNAを検出し、なおかつ増殖がまだ続いていたことを突き止めた研究。
— Angama (@Angama_Market) February 23, 2022
◆Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long COVID-19
【Research Square 2022年2月22日】
Abstract
The World Health Organization has defined long COVID-19 (LC) as a condition where patients exhibit persistent symptoms over time after its acute phase, which cannot be explained by alternative diagnosis. Since we have previously reported residual viral antigens in tissues of convalescent patients, we now aim to assess the presence of such antigens in post-convalescent tissues. Here, we established the presence of residual virus within the appendix and breast tissue of 2 patients who exhibited LC symptoms, 175 to 462 days upon positive diagnosis, using immunohistological techniques. We observed positive staining for viral nucleocapsid protein (NP) in the appendix, and tumour-adjacent region of the breast, but not within the tumour via multiplex immunohistochemistry. Notably, with RNAscope, both positive-sense and negative-sense (replicative intermediate) viral RNA were detected. As a single-stranded virus, SARS-CoV-2, have to produce a replicative intermediate as a template to synthesize new genomic RNAs. Thus, the detection of negative-sense viral RNA suggests ongoing viral replication. While viral RNA and antigen from gastrointestinal and stool samples of convalescent patients has been extensively reported, we believe this is the first study to detect viable virus. Furthermore, our positive finding in the breast tissue also corroborated with recent reports that immunocompromised patients had also experienced LC symptoms and persistent viral replication. Overall, our findings, along with emerging LC studies, question the possibility of the gastrointestinal tract functioning as a reservoir.