嗅觉丧失、结膜炎及发烧 （新冠讲座44）

嗅觉丧失、结膜炎及发烧 （新冠讲座44）

Anosmia & Conjunctivitis in COVID-19, Is Fever Helpful (Lecture 44)

Welcome to another MedCram COVID-19 update. We are headed to a half a million total confirmed worldwide, over 20,000 deaths, and 115,000 total recovered with most of that growth outside of China at this point. If we look at the Worldometer website, most of the deaths that are occurring are in Italy and Spain with the United States starting to move up as well.

欢迎来到MedCram COVID-19的另一个更新。在全球范围内，我们已确认的总数为500万，死亡人数超过20,000，目前已恢复115,000，其中大部分增长来自中国境外。如果我们查看Worldometer网站，大多数死亡事件都发生在意大利和西班牙，而美国也开始上升。

The number of new cases in Italy looks as though might have peaked. We’ll have to see more in the future in terms of its direction. While the total deaths in Italy continue to escalate, over in the United States the total number of cases continues to grow. Total number of deaths is over a thousand here in the United States already.

意大利的新病例数量似乎已经达到顶峰。在未来的发展方向上，我们将不得不看到更多。尽管意大利的总死亡人数继续上升，但美国的总病例数却继续增加。在美国，死亡总数已经超过一千。

New York City seems to be the epicenter of what’s going on here in the states. They are predicting that the peak number is still about two to three weeks away in New York. Remember that New York is ahead of just about everybody else. Of course, if we were able to flatten the curve, then that’s going to delay that even more, but hopefully, the peak won’t be as high.

纽约市似乎是各州正在发生的事情的中心。他们预测纽约的高峰期仍在两到三周左右。请记住，纽约领先于其他所有人。当然，如果我们能够使曲线变平，那么这将进一步延迟，但希望峰值不会那么高。

Okay, I want to talk to you about a couple of updates in terms of signs and symptoms. This is from the American Academy of Ophthalmology, which is warning us that there have been several reports that the virus may cause conjunctivitis and possibly be transmitted by aerosol contact with the conjunctiva. The academy is recommending protection from the mouth, nose and eyes when caring for patients potentially infected with SARS-CoV-2.

好吧，我想和您谈谈一些迹象和症状方面的更新。这是来自美国眼科学院的，它警告我们，已有几篇报道说该病毒可能引起结膜炎，并可能通过与结膜的气溶胶接触传播。该科学院建议，在照顾可能感染SARS-CoV-2的患者时，应避免口腔，鼻子和眼睛。

Also, there are recommendations on how to sterilize the equipment that’s used. The other name for conjunctivitis is pink eye. It’s not uncommon to have conjunctivitis when you have an upper respiratory viral infection, so be aware of that.

此外，还有关于如何对使用的设备进行消毒的建议。结膜炎的别称是红眼病。上呼吸道病毒感染并发结膜炎并不少见，所以要注意这一点。

The other sign and symptom is related to the loss of smell as a marker of COVID-19 infection. This is a letter that was written by the president of the Ear, Nose and Throat Association in the UK, Dr. Kumar. He’s talking here about post-viral anosmia that by itself is not unusual. What they’re seeing, however, is a huge rise in the number of patients that are complaining of the inability to temporarily smell after a viral infection. They mention here that in South Korea where testing has been more widespread, 30% of patients testing positive have had anosmia as their major presenting symptom in otherwise mild cases.

其他症状和体征与作为COVID-19感染标志物的气味消失有关。这是英国耳鼻喉协会主席库马尔博士写的信。他在这里谈论的是后病毒性贫血，这本身并不罕见。然而，他们所看到的是抱怨病毒感染后无法暂时闻到气味的患者人数激增。他们在这里提到，在韩国，测试更为广泛，在其他情况下，轻度病例中30％呈阳性的患者主要表现为失眠。

On the flip side of that, they’re also noticing that patients without any other signs or symptoms consistent with asymptomatic COVID-19 are presenting with the only sign being anosmia, and that may be suggestive of asymptomatic infection with COVID-19. He’s talking about him personally having seen 4 patients in one week all under the age of 40, and otherwise asymptomatic except for the recent onset of anosmia. He usually sees only about once a month, so this is something to be on the lookout for.

另一方面，他们还注意到没有其他症状或体征与无症状COVID-19一致的患者出现的唯一症状是失眠，这可能暗示了COVID-19的无症状感染。他是在谈论自己一个星期内见过4名年龄均在40岁以下的患者，其他方面无症状，除了最近发生的失眠症。他通常每个月只看一次，所以需要注意这一点。

He also has some recommendations at the bottom of the letter. He says that there is potential that if any adult with anosmia but no other symptoms was asked to self-quarantine for seven days, in addition to the current symptom criteria used to trigger quarantine, we might be able to reduce the number of otherwise asymptomatic individuals who continue to act as vectors, not realizing the need to self-isolate.

他在信的底部还提出了一些建议。他说，如果有任何患有嗅觉异常但没有其他症状的成年人被要求进行自我隔离有7天的可能性，那么除了当前用于触发隔离的症状标准外，我们还可以减少原本没有症状的个体的数量他们继续充当媒介，却没有意识到自我隔离的必要性。

It would also be an important trigger for healthcare personnel to employ full PPE or personal protective equipment and help to counter the higher rates of infection found amongst ENT surgeons compared to our other health care workers. Of course, we’ll put links to these articles as well as other ones in the description below.

与我们其他医护人员相比，这也将是医护人员使用全套个人防护设备或个人防护设备的重要诱因，并有助于应对耳鼻喉外科医生中更高的感染率。当然，我们将在下面的描述中放置这些文章以及其他文章的链接。

So we’re going to talk about the immune system as promised. Remember what we talked about how a good immune system in both of these situations could help not only the person having the good immune system, but also reducing the number of people going into our healthcare system.

因此，我们将按照承诺谈论免疫系统。记住我们在这两种情况下谈论好的免疫系统如何不仅可以帮助拥有良好免疫系统的人，而且可以减少进入我们的医疗保健系统的人数。

So here is what is represented as the population at a whole, and then there is a certain amount that will catch the infection which is here, and then about 80% of those people will not need to go to the hospital because they have a sufficient immune system, but the 20% here we could improve, and perhaps if we had a good immune system we might be able to not even become infected in the first place.

因此，这里是整体人口的代表，然后有一定数量的人会感染这里的感染，然后这些人中的大约80％不需要去医院，因为他们有足够的免疫系统，但这里有20％的人可以改善，也许如果我们拥有良好的免疫系统，我们也许一开始就不会被感染。

We talked about in our last update what they were doing by giving a BCG vaccine even if they were given one earlier in life to give another one, they’re hoping to see that their immune system will be heightened not just against tuberculosis as it’s designed for, but also an improvement in your innate immune system. So that’s your lymphocytes, your leukocytes, your natural killer cells, your neutrophils Etc. What is it that we can do to improve our own immune system?

我们在最后一次更新中谈到了他们通过接种BCG疫苗所从事的工作，即使他们在生命的早期就接种了BCG疫苗，他们也希望看到他们的免疫系统将不仅按照设计的结核病得到增强可以改善先天免疫系统。那就是您的淋巴细胞，您的白细胞，您的自然杀伤细胞，您的中性粒细胞等等，我们可以做些什么来改善自己的免疫系统？

So the first thing I want to talk about is fever. Fever is one of those signs that you get when you have a viral infection, and it’s one of those things that you might see also with COVID-19, although it’s not universal.

所以我想谈的第一件事是发烧。发烧是病毒感染时出现的症状之一，也是COVID-19可能会出现的症状之一，尽管它并不普遍。

So here’s a paper that was published in 2017 looking at the presence of fever in adults. One of the things in the article that’s interesting to note is they looked at a number of different viruses, and you can see here for coronavirus. If we were to take this as a representative of the current COVID-19 cases, only two out of seven cases presented with fever, giving it about a 28% incidence of fever.

因此，这是一篇于2017年发表的论文，着眼于成年人发烧的存在。文章中值得注意的一件事是，它们研究了许多不同的病毒，您可以在此处看到冠状病毒。如果将其作为当前COVID-19病例的代表，那么七分之二的患者会发烧，这使其发烧的发生率约为28％。

In the discussion, they say here we have shown using prospectively collected data that the rate of fever in adults with confirmed viral respiratory infections is much lower than described in children. Nevertheless, it is present and it would behoove us to take a look at the mechanisms of fever both in adults and children.

在讨论中，他们说，这里我们使用前瞻性收集的数据表明，确诊为病毒性呼吸道感染的成年人的发烧率比儿童中描述的低得多。尽管如此，它仍然存在，我们应该去看看成人和儿童发烧的机制。

So here’s another paper that was published in the World Journal of Clinical Pediatrics back in 2012 titled: Fever management, evidence versus current practice. I found it to be a very good source of some interesting studies regarding fever. Under the heading that says evidence that fever is beneficial, they had a number of points. It talks about fever having an adverse effect on bacteria, on viruses, how it improves the activity of a lot of signaling like interleukin 1, also cells that are involved in the immune system that we’ve talked about, including T cells, B cells and antibody production.

因此，这是另一篇发表在2012年《世界临床儿科杂志》上的论文，标题为：发烧管理，证据与当前实践。我发现它是一些有关发烧的有趣研究的很好的来源。在说出发烧有益的证据的标题下，他们有很多要点。它谈到发烧会对细菌，病毒产生不利影响，它如何改善白介素1等许多信号传导的活性，也涉及我们讨论过的免疫系统中涉及的细胞，包括T细胞，B细胞和抗体生产。

A lot of these things are mediated at temperatures that are just above normal around 38, 39, 40°C. 38°C correlates to about a 100.4 F. There are also some studies here that show that interferon, which is of course an antiviral agent, has enhanced antiviral activity above 40°C. So there are a number of references here and I’ll include all of those papers in the description below.

许多（病例和症状）是在38、39、40°C左右高于正常的温度下产生的。 38°C约等于100.4F。这里还有一些研究表明，干扰素（当然是一种抗病毒剂）在40°C以上具有增强的抗病毒活性。因此，这里有许多参考资料，我将在下面的描述中讨论所有这些论文。

In those references, we can see here in vitro that, as we increase the temperature here on the x-axis, the percent yield in this case of poliovirus starts to drop. Similarly, if we look at the development of poliovirus at 37°C in that paper, it was quite prolific over a period of time. Repeat the experiment here at 40°C, there is a precipitous drop. Again, these are in vitro studies, so let’s look at some human studies.

在那些参考文献中，我们可以在体外看到，随着我们在x轴上升高温度，在这种情况下，脊髓灰质炎病毒的产量百分比开始下降。同样，如果我们观察那篇论文脊髓灰质炎病毒在37°C时的发育情况，它在一段时间内它的繁殖力也很高。在40°C重复此处的实验，有一个急剧下降。同样，这些是体外研究，因此让我们看一些人体研究。

So, while there have been a lot of bacterial studies, I want to highlight a viral study with rhinovirus, which is a virus that causes a common cold as well. This paper was published back in 1990. There were 56 healthy subjects and all of them had rhinovirus introduced into them. But then there were four arms; there was an aspirin arm, there was a Tylenol arm, there was an ibuprofen arm and then there was a placebo arm.

因此，尽管进行了许多细菌研究，但我想重点介绍鼻病毒的病毒研究，鼻病毒也是一种引起普通感冒的病毒。该论文发表于1990年。共有56名健康受试者，所有受试者都感染了鼻病毒。但是那时有四组实验。有一个阿司匹林实验，一个泰诺实验，一个布洛芬实验，然后一个安慰剂实验。

And in each of these arms, they measured something called a serum neutralizing antibody response. So we’re looking for the antibody response after these people that were infected with rhinovirus. And what they found is that in the aspirin and in the Tylenol group, these together were statistically significantly lower in terms of that antibody response when it was compared to placebo and that P value was less than .05.

在每个实验上，他们都测量了一种称为血清中和抗体反应的物质。因此，我们正在寻找感染了鼻病毒的这些人后的抗体反应。他们发现，与安慰剂相比，阿司匹林和泰诺组的抗体反应在统计学上低得多，P值均小于0.05。

And what we’re finding more and more recently is that temperature is intricately related to the immune function of the cell. Here’s a paper that was published in 2018 that shows that temperature regulates certain cellular messaging systems that allow the immune system to respond to infections. The signaling pathway known as NF-κB is a signaling mechanism that allows the cell to respond to these infections.

最近，我们越来越发现，温度与细胞的免疫功能密切相关。这是2018年发表的一篇论文，显示温度调节某些细胞信息传递系统，使免疫系统能够对感染做出反应。被称为NF-κB的信号传导途径是一种信号传导机制，可使细胞对这些感染做出反应。

And it was recently highlighted in an article in Medical News Today, a signaling pathway called Nuclear Factor kappa B plays an important role in the inflammation response in the context of infection or disease. This protein helps the expression and the production of certain immune cells.

最近在《今日医学新闻》上的一篇文章中强调了这一点，一种被称为核因子κB的信号传导途径在感染或疾病的炎症反应中起着重要作用。这种蛋白质有助于某些免疫细胞的表达和产生。

These proteins respond to the presence of viral or bacterial molecules in the system and that is when they start switching relevant genes related to the immune response at the cellular level. They also note here that this NF-κB becomes more active at higher temperatures and less active at lower temperatures.

这些蛋白质对系统中病毒或细菌分子做出反应，也就是说，当它们开始在细胞水平上转换与免疫反应相关基因时。他们在这里还注意到，该NF-κB在较高温度下变得更有活性，而在较低温度下变得较弱。

So the question is, is it the fever that’s causing the NF Kappa beta to go up or is it the NF Kappa beta that’s causing the fever. Well, they did some experiments and they found this protein called the A20 protein is what tells the NF-κB protein to go up. And so if you knock out this A20, then that is going to prevent the NF-κB from activating, and when it doesn’t it’s no longer going to be doing the things that it needs to do to augment the immune system.

所以问题是，是发烧导致NF Kappa beta升高还是NF Kappa beta导致发烧。不过，他们做了一些实验，他们发现这种叫做A20蛋白的蛋白质告诉NF-κB蛋白上升。因此，如果摧毁此A20，则将阻止NF-κB激活，而当它不激活时，它将不再在执行其增强免疫系统所需的操作。

So in essence, fever somehow stimulates A20, which then stimulates NF-κB, and NF-κB is essential for immune system. How do we deal with fever? Well, remember what we talked about a couple of lectures ago. We have something called arachidonic acid, which is converted into prostaglandin and specifically prostaglandin E2, that’s mediated through something called the COX-2 enzyme. And what are one of the big inhibitors of the COX-2 enzyme? but NSAIDs. Remember what NSAIDs are, aspirin, ibuprofen and indomethacin.

因此，从本质上讲，发烧会以某种方式刺激A20，然后刺激NF-κB，而NF-κB对免疫系统至关重要。我们如何应对发烧？不过，请记住我们之前几个讲座中谈到的内容。我们有一种叫做花生四烯酸的物质，它被转化为前列腺素，特别是前列腺素E2，是通过一种被称为COX-2酶介导的。什么是COX-2酶的最大抑制剂之一？就是非甾体抗炎药。记住什么是非甾体抗炎药，阿司匹林，布洛芬和消炎痛。

So because of this and other studies, many scientists and many practitioners, especially in the pediatric population, are advocating that fevers based on known viral infections shouldn’t be treated just based on the number itself and the fact that the temperature is elevated. That in fact the fever may actually be beneficial to the recovery of the patient and unless the fever is excessive, or the patient is dehydrated, or there’s lethargy, which means that the patient doesn’t want to move very much, then fever shouldn’t be treated.

因此，根据这项研究和其他研究，许多科学家和许多从业者，尤其是在儿科研究者中，提倡不应仅根据数量本身和温度升高的事实来治疗基于已知病毒感染的发烧。实际上，发烧实际上可能对患者的康复有益，除非发烧过度或患者脱水或嗜睡，这意味着患者不想活动太多，否则不应进行治疗。

A couple of points here to remember, number one a fever is not hyperthermia. Hyperthermia is what one might get if they were running on a very hot day and their temperature was 105, 106, 107. Those are clearly very dangerous temperatures and they need to be treated aggressively; otherwise, someone could die. But in the sense where there is a viral infection and a fever is being caused and there’s no other complication as a result of that fever, there is a question about whether or not that fever should be treated.

这里要记住几点，首先发烧不是体温过高。如果在炎热的天气中奔跑，并且温度分别为105、106、107，可能会导致体温过高。这些温度显然是非常危险的温度，需要积极治疗，否则可能会导致死亡。但是从某种意义上说，当有病毒感染并引起发烧，而没有因发烧产生并发症时，那我们就要问一个问题，即是否应该治疗发烧。

The other point I want to make and it’s very important is that there are a number of adults in this country that are on aspirin for very good reasons and this is not a reason to stop it. You should never stop any medication without consulting your physician. There are people with stents, people with strokes, for which aspirin is lifesaving. Not to mention that people take ibuprofen and indomethacin for rheumatological conditions as well. I’m simply saying that perhaps an elevated temperature in your body may be part of the solution to getting better over the viral infection and not part of the problem.

我要说的另一点，非常重要的是，这个国家有很多成年人出于很好的理由服用阿司匹林，这并不是说要停止服用阿司匹林。在未咨询医生之前，切勿停止任何药物治疗。有带支架的人，有中风的人，阿司匹林可以挽救生命。更不用说人们也因风湿病而服用布洛芬和消炎痛。我只是说，也许您体内的高温可能是解决病毒感染问题的一个方法，而不是问题的一部分。

I would be interested in your comments below regarding this issue. I think one of the conclusions that I draw from this is that there is a benefit in infectious disease to having an elevated body temperature.

对于您在以下有关此问题的评论，我会很感兴趣。我认为从中得出的结论之一是，体温升高对传染病有好处。

Thanks for joining us.

感谢加入我们。