與免疫、凝血和發炎有關的蛋白質可能有助於揭示長期新冠病毒的複雜性。
Miryam Naddaf / 2024 年 1 月 18 日 / 新聞 / Nature
長新冠的特徵是疲勞和腦霧等症狀，這些症狀在 SARS-CoV-2 感染後可能會持續數月或數年。
圖片來源：Jovelle Tamayo/《華盛頓郵報》，來自 Getty
研究人員開發了一種計算模型，根據對血液中 6,500 多種蛋白質的分析，預測一個人患上長新冠肺炎的可能性有多大。
在1 月18 日發表在《Science》上的一項研究中，研究小組將COVID-19 檢測呈陽性的人的血液樣本與健康成年人的血液樣本進行了比較，發現長新冠患者、康復者和從未被感染的人的蛋白質組成有顯著差異。
長新冠的研究可能會失去動力——我們需要一次登月計劃
分析顯示，參與免疫反應、凝血和發炎的蛋白質可能是診斷和監測長新冠的關鍵生物標誌物，全球估計有 6500 萬人受到新冠病毒的影響。
這種情況與 200 多種症狀有關，包括腦霧、疲勞、胸痛和呼吸困難，這些症狀可能在 SARS-CoV-2 感染後持續數月或數年。
倫敦帝國學院的呼吸內科醫生 Aran Singanayagam 表示，這項小型研究有望為進一步的研究鋪平道路，以嘗試開發治療方法，以治療目前幾乎不可能治療的疾病」。
蛋白質模式
研究包括39 名從未檢測出COVID-19 呈陽性的健康成年人，以及113 名曾檢測出陽性的人，其中40 人患有長期COVID（定義為症狀在初次感染後6 個月內持續存在）。其中 22 人在首次檢測呈陽性後 12 個月後仍出現症狀。
研究人員分析了 268 個血液樣本中的 6,596 種蛋白質，這些樣本分別在急性期和六個月後從參與者身上採集。他們發現，長期感染新冠病毒的人與未感染新冠病毒的人的血液存在一些差異，包括參與凝血和發炎的蛋白質不平衡。
與健康參與者和從COVID-19 中完全康復的參與者相比，長期感染新冠病毒的人體內一種名為抗凝血酶III 的蛋白質水平較低，這種蛋白質有助於預防血栓，而血小板反應蛋白-1 和血管性血友病因子的蛋白質水平較高。兩者都與血栓形成有關。
長新冠治療：為什麼世界仍在等待
當他們檢查一部分參與者的血球時，研究人員發現，白血球上一種名為 CD41 的蛋白質的表達在健康人中最低，而在患有 12 個月新冠肺炎的人中最高。
CD41 通常存在於血小板（參與凝血的細胞碎片）上，它在白血球上的存在顯示這些細胞的異常聚集。巴黎巴斯德研究所的免疫病毒學家麗莎·查克拉巴蒂（Lisa Chakrabarti）說：「這可能會導致微凝塊的形成」。一些科學家認為，這些微小的血塊可能會阻礙氧氣流向組織，導致一些長期的新冠症狀。
研究人員還發現，長期感染新冠病毒的人在初次感染期間和六個月後，補體系統（人體免疫防禦的一部分，通常有助於清除感染）的活化程度增加。與完全康復或健康的參與者相比，患有六個月新冠肺炎的人的補體系統中某些蛋白質的水平降低，而其他蛋白質的水平升高。研究報告的合著者、瑞士蘇黎世大學的醫生兼科學家卡洛·切爾維亞–哈斯勒 (Carlo Cervia-Hasler) 表示，這些蛋白質的不平衡可能會導致組織損傷。
然後，研究人員利用機器學習創建了一個模型，根據參與者血液中的蛋白質水平以及年齡和體重指數等其他因素來預測參與者是否會患上長期新冠肺炎。當應用於單獨的數據集時，該模型在預測哪些參與者將患有 12 個月的新冠肺炎方面上表現良好。
「我們才剛開始」，切爾維亞–哈斯勒說，該團隊的一些發現與關於長新冠病因的現有理論非常吻合，並且「可能會開啟有關可能有所幫助的[療法]的新研究」。
但該分析僅涉及相對較少的參與者，並且沒有找出這種情況的根本原因，而這一直是開發治療方法的關鍵障礙。「我們正處於探索這個新興領域的開始，」查克拉巴蒂說。
辛加納亞加姆補充說，由於長新冠會涉及一系列症狀，因此可能有幾個潛在原因對人們產生不同的影響。「該症候群的異質性可能意味著需要進行更大規模的研究」，他說。「這不會是所有這些症狀背後的單一機制」。doi：https://doi.org/10.1038/d41586-024-00158-w
參考文獻：
1. Cervia-Hasler. C et al. 《科學》 383，eadg7942 (2024)。
Long-COVID signatures identified in huge analysis of blood proteins
Proteins involved in immunity, clotting and inflammation could help to unravel the complexity of long COVID.
Miryam Naddaf / 18 January 2024 / NEWS / Nature
Long COVID is characterized by symptoms such as fatigue and brain fog, which can persist for months or years after SARS-CoV-2 infection.Credit: Jovelle Tamayo/The Washington Post via Getty
Researchers have developed a computational model that predicts how likely a person is to develop long COVID, based on an analysis of more than 6,500 proteins found in blood.
In a study published on 18 January in Science, the team compared blood samples from people who tested positive for COVID-19 with ones from healthy adults, and found notable differences in the composition of proteins in people with long COVID, those who recovered and those who were never infected.
Long COVID research risks losing momentum — we need a moonshot
The analysis suggests that proteins involved in immune responses, blood clotting and inflammation could be key biomarkers in diagnosing and monitoring long COVID, which affects an estimated 65 million people worldwide.
The condition has been linked to more than 200 symptoms, including brain fog, fatigue, chest pain and breathlessness, which can persist for months or years after a SARS-CoV-2 infection.
The small study “will hopefully pave the way for further studies to try and develop therapies for what is, at the moment, pretty much an impossible thing to treat”, says Aran Singanayagam, a respiratory physician at Imperial College London.
Protein patterns
The study included 39 healthy adults who had never tested positive for COVID-19 and 113 people who had, of whom 40 had long COVID, defined as having symptoms persist 6 months after initial infection. Of those, 22 still had symptoms 12 months after first testing positive.
The researchers analysed 6,596 proteins across 268 blood samples, which were collected from participants once during the acute phase and again six months after. They found several differences in the blood of people with long COVID compared with those without it, including an imbalance in proteins involved in blood clotting and inflammation.
Compared with healthy participants and those who had fully recovered from COVID-19, people with long COVID had lower levels of a protein called antithrombin III, which helps to prevent blood clots, and higher levels of the proteins thrombospondin-1 and von Willebrand factor, both of which are associated with clot formation.
Long-COVID treatments: why the world is still waiting
When they examined blood cells from a subset of participants, the researchers found that the expression of a protein called CD41 on white blood cells was lowest in healthy people and highest in people who had 12-month long COVID.
CD41 is typically found on platelets — cell fragments involved in clotting — and its presence on white blood cells indicates abnormal clumping of these cells. “That could contribute to microclots,” says Lisa Chakrabarti, an immunovirologist at the Pasteur Institute in Paris. Some scientists think that these tiny blood clots could be the cause of some long COVID symptoms by blocking oxygen flow to tissues.
The researchers also found increased activation of the complement system — part of the body’s immune defences which normally help in clearing infections — in people with long COVID, both during initial infection and six months later. People with six-month long COVID had reduced levels of some proteins involved in the complement system and elevated levels of others, compared with fully recovered or healthy participants. An imbalance of these proteins could cause tissue damage, says study co-author Carlo Cervia-Hasler, a physician–scientist at the University of Zurich, Switzerland.
Using machine learning, the researchers then created a model to predict whether a participant would develop long COVID on the basis of the protein levels in their blood, along with other factors such as age and body mass index. When applied to a separate data set, the model performed well in predicting which participants would have 12-month long COVID.
‘We are at the beginning’
Some of the team’s findings fit well with existing theories on the causes of long COVID, and