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’s 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.

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 polio virus 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.

So while there have been a lot of bacterial studies, I wanted 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 was 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.

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.

And what we’re finding more and more of 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.

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.

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.

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.

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.

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.

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.

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. 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.

Thanks for joining us.

MedCramChina

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