Multiple factors play a role in complex diseases like COVID, and knowing what they are is important for predicting how different people will be affected.
在类似于新冠肺炎的复杂疾病中，会有很多因素在发挥作用。了解这些因素是什么对于预测人们会受到何种影响具有重要意义。
Early on in the pandemic, being older, overweight, or smoking were identified as increasing your risk of developing severe COVID. This then informed public health decisions – the elderly were prioritized in the vaccine rollout, for example.
在疫情初期，年老者、超重者或吸烟人士都被认为是患重症新冠肺炎的高危人群。这一发现为公共卫生决策提供了依据-比如，年老者安排优先接种疫苗。
But there are other biological factors involved in COVID that are less well understood. Consider, for example, the thousands of proteins with different functions that circulate in your blood.
但是，在新冠肺炎中，还存在其他不被人们熟知的生物因素。比如，成千上万个在血液中流动的、具有不同作用的蛋白质。
Some play a role in the body’s defense against viruses, others transport molecules around the body, or act as messengers to distribute information.
一些蛋白质的作用是抵御病毒，其他则负责将分子运送至身体各处，或作为信使传递信息。
Through these functions, these proteins can impact the development and severity of COVID – and crucially, we don’t all have the same amounts of them inside us.
通过发挥不同的作用，这些蛋白质可以影响新冠肺炎的进程和病情程度-而且最为关键的是，我们每个人血液中的蛋白质含量都不一样。
This is why people develop different forms of COVID: some get a runny nose or fever, while others need to go to hospital. An unlucky few may need intensive care, and in the severest cases, some may die.
这就是为什么患上新冠肺炎的人们会出现不同的症状：有些人会流鼻涕或发烧，而另一些人则需要前往医院。更为不幸的少数可能需要重症监护。而在最严重的情况下，有些人可能会因此而离世。
As the number of proteins in the human body is so large, it’s difficult to pinpoint the exact proteins and biological systems that cause these different outcomes. Nevertheless, this is what our team aimed to do.
由于人体内的蛋白质数量十分庞大，因此很难找到引起不同症状的具体的蛋白质和生物系统。尽管如此，我们的团队还是设法实现这一目标。
We explored more than 3,000 blood proteins using a technique called Mendelian randomization.
我们利用一种叫做孟德尔随机化法的技术研究了超过3000种血液蛋白。
This is where, instead of directly measuring something that you think has an effect on a disease (in this case, a blood protein) and then seeing if levels of it correlate with disease severity, you instead look at variation in the genes that influence that substance’s levels, and examine how this affects disease outcomes.
与直接测量你认为对疾病有影响的因素（在这里是指血液蛋白），然后查看是否该因素处于不同水平时会与疾病严重程度有关联不同，在该方法中，你所观察的是影响这些因素处于不同水平的基因变化，然后研究这些变化如何对疾病产生影响。
This is because if you look at blood protein levels directly, you can’t be sure that other outside factors – like lifestyle choices, or even having COVID – aren’t affecting them at the point in time when you’re measuring them.
这是因为，如果你直接观察血液中的蛋白质水平，你无法确定其他的外在因素（比如生活方式或甚至患上新冠肺炎）不会在你进行测量的时候对它们产生影响。
Genes, on the other hand, don’t change during someone’s lifetime. They therefore allow you to more reliably identify people with high and low levels of the substances you’re interested in, and so make more robust estimates of how something like a blood protein affects a disease like COVID.
另一方面，在人的一生中，基因不会发生改变。因此，你可以通过自己所关注的不同因素处于高低水平来可靠地辨识一个人并从而对血液蛋白质如何对新冠肺炎这类疾病产生影响而做出更加有信心的估测。
First, we had to identify which genes are associated with different blood proteins. We did this by looking at the results of genome-wide association studies.
首先，我们需要发现哪些基因与不同的血液蛋白有关。我们通过查看全基因组关联研究的结果找到了这些血液蛋白。
These are large pieces of research that look at genetic and biological differences across many people, to trace the links between genetic variants and certain characteristics. Large-scale genome-wide results have also been able to trace links between genes and the risk of severe COVID too.
大量研究通过观察不同人之间基因和生物的差异性来发现基因变体和某些特点之间的联系。全基因组关联研究也可以发现基因和新冠肺炎重症之间的联系。
Analyzing this data, we identified several proteins that potentially increase or decrease the risk of severe COVID.
通过分析这一数据，我们发现了数个会潜在增加或减少新冠肺炎重症风险的蛋白质。
For example, we found that increased levels of a protein called FAAH2 may increase the risk of someone needing hospital treatment for COVID. FAAH2 causes cells to absorb and inactivate substances called endocannabinoids.
比如说，我们发现，一种叫做FAAH2的蛋白质的水平升高可能会增加新冠患者住院治疗的风险。FAAH2会引起细胞吸收并灭活一种叫做内源性大麻素的物质。
These have anti-inflammatory effects, and studies have even suggested they could be used as treatments for COVID. This would explain why having more proteins that remove them is problematic – this potentially lessens the body’s ability to control inflammation caused by COVID.
这类物质具有抗炎作用，研究甚至还表明，这些物质可以用于治疗新冠肺炎。这可能解释了为什么血液中有更多移除这类物质的蛋白质会造成问题-这会潜在抑制身体对抗由新冠肺炎引起的炎症的能力。
Another influential protein we identified was the ABO enzyme. This determines your blood group and is a hot topic in COVID research. Our study showed that having higher levels of the ABO enzyme appears to increase the risk of being hospitalized with COVID and subsequently needing intensive care.
我们所发现的另一外具有重要作用的蛋白质叫做ABO酶。这种蛋白质能够测定你的血型，其同时也是新冠肺炎研究的重点。我们的研究发现，ABO水平升高似乎会增加新冠肺炎患者住院并随后需要重症监护的风险。
Previous small studies have shown that blood group A is more common in those with severe COVID. Our findings strengthen the case that the ABO enzyme and blood type influence COVID severity.
此前的小规模研究发现，A型血在新冠肺炎重症患者中间更常见。我们的研究结果强化了这一说法，即ABO酶和血型会对新冠肺炎的严重程度有影响。
COVID can also cause disease in the blood vessels, particularly when severe. But we found that proteins that attract white blood cells to the wall of blood vessels appear to be protective against severe COVID.
新冠肺炎还会引起血管方面的疾病，特别是当其比较严重时。但是，我们发现，将白细胞吸引到血管壁上的蛋白质似乎对新冠肺炎重症具有保护作用。
Attracting more white blood cells like this has long been known to improve the immune response in blood vessel walls, and in COVID specifically this seems to help fight off infection.
Identifying these risk factors may help scientists develop new treatments, as these proteins could be targeted by new medicines (or existing ones that have been repurposed).
人们很早就知道像这样吸引更多的白细胞可以改善血管壁的免疫应答，而在新冠肺炎中，其似乎有助于对抗感染。发现这些危险因素也许有助于科学家制定新的治疗方法，如同我们可以采用新型药物（或现有的经过稍加修改的药物）来对付这些蛋白质。
It has also allowed us to draw up a list of proteins that can be prioritized by other researchers, so that in future we can understand even more about what the biological risk factors for COVID are.
该研究也使得我们列出可以被其他研究者优先考虑的蛋白质清单，因此在未来我们可以了解更多新冠肺炎的生物风险因素。
来源：ScienceAlert
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