模型认为大部分低危感染人患者，病毒慢慢run the course, 免疫系统逐步建立，这样病毒发起总攻的时候，免疫已经“到位”。 年轻人中不少类似意大利1号患者的rapid转重症/危重插管的例子。（回顾：30+运动达人，潜伏期踢球马拉松，rapid转重症迅速危重插管，震惊欧洲）。模型认为其剧烈运动气喘吁吁导致的大量病毒从上呼吸道“冲”到下呼吸道，在免疫未“部署到位”前“总攻”肺泡，是rapid转重的原因。同时留给医生的window很小，极危险。
论文的abstract The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19. ---------------论文关于剧烈运动的核心内容--------- 4.4 - – Strenuous physical exercise 剧烈运动 两条 Strenuous exercise and IgA defect Deep inhalation while performing strenuous exercise (running in particular) and virusspread to lower airways and alveoli 这一段的摘抄 4.4.1 Strenuous exercise and IgA defectRegular, moderate exercise is associated with a reduction of the severity of acute respiratoryinfections [63], salivary IgA levels decline in athletes during and after a training season.[64]This observation may explain why elite athlete are at higher risk of upper airway infections.[65]A so-called ``open window'' of period is ranging between 3 and 72h hours after the strenuousexercise is finished.[66] 4.4.2 Deep inhalation while performing strenuous exercise (running in particular) and virusspread to lower airways and alveoliAerosols are considered an important mode of transmission for influenza.[67] Duringstrenuous exercise, requiring up to 40 l/min of respiratory flow, oronasal (combined nose andmouth) breathing dominates, with the oral component reaching up to 60% of the overallvolumes.[67] High flow air and change of breathing from nose to mouth breathing inducesprogressive cooling and drying of the respiratory tract mucous. Decreasing movement ofciliated cells and increasing mucosal viscosity, finally impairing filtering of microorganismsfrom the upper respiratory tract system.[68]The pattern of breathing during strenuous exercise changes dramatically by a tremendousincrease of ventilation (i.e.: inspiratory and expiratory volumes of air), and of alveolarventilation in particular. Obviously, these changes mostly attain to whatever kind of runnersbelonging to all sport disciplines, being semi-professional and professional athletesparticularly exposed (such as much more than individuals of common population) due to theirfrequent practice of extreme and long-lasting exercise. Furthermore, the majority of theseathletes have their lungs that usually work in perfect physiological conditions, such as veryclose to those of the “ideal lung”. In other words, in the absence of any anatomical orphysiological factor causing a significant unevenness in distribution of their alveolarventilation. Paradoxically, these pre-existing ideal conditions significantly favor the deepinhalation of several irritants, allergens, infectious agents. Even the SARS-CoV-2 can thenspread more easily to the deepest areas of the lungs (alveolar bronchioles and alveoli) during strenuous exercise, and there start its aggressive action. Not by chance, a great proportion ofprofessional football players claimed the occurrence of fever, dry cough and malaise (anddyspnea in some cases) immediately after, or a few hours following their last official match.
在后面关于“Triggers of the cascades leading to ARDS and respiratory failure" 俗称“重症的导火索”这一段里面 提出了模型的重要假说 这里面的关于IgA IgM IgG的观点现在很多地方都有提到（虽然我也不大理解） An intriguingobservation is that ARDS symptoms start in coincidence with the onset of the SARS-CoV-2antibody specific immune response. Interestingly, the serum levels of specific IgA, IgM, andIgG are the highest in patients with the worst clinical course. [30,100] We may hypothesizethat in individuals in whom the virus early reaches the lung and actively replicates, a robustPreprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 24 April 2020 13adaptive immune response contributes to the tissue damage and severity of the pneumonia.This hypothesis may contribute to explain why patients with agammaglobulinemia had a mildpneumonia and recovered without experiencing complications requiring oxygen therapy.[101] Antibody may be simply a bystander consequence of a powerful viral replication, orrather the direct trigger of a severe inflammation. 值得注意的是这里特地提到了ADE 并没有rule it out.排除这个可能。
第九条是论文核心模型“ A model of the interaction between SARS-CoV-2 and immune system”
First stage (upper airways): viral clearance or pneumonia - 第一阶段上呼吸道感染。三个scenarios分别是“年轻健康人”“老人”“年轻但是大剂量暴露”
Second stage (pneumonia): recovering or complications. 第二阶段肺炎-这里是核心重点 If the virus reaches the alveoliwell after the establishment and expansion of a very efficient adaptive immuneresponse, the patient will probably never require oxygen and will not undergocomplications.By contrast, if the virus infects the alveoli early enough (i.e. already 7 days from theinfection or 2-3 from the first symptoms), the chances of a better replication in the lungare higher. When the specific response is established, massive amount of the virus caninteract with massive amounts of antibodies with high affinity. 如果病毒感染肺泡的时间点足够早（比如感染后7天，或者症状出现的2-3天），那么病毒在肺部大量复制的机会更高。 后面介绍了4种pathway，大量术语。
划重点：对诊断，公共卫生和临床干预的意义 Implications for diagnosis, public health and clinical intervention -声明要小心谨慎，因为对于新冠的各种研究都是初步的不完全的- 如何预防重症 - Prevention of severe infections 10.2.1 通过定量PCR或快速测试来找出有症状或者无症状的高剂量病毒传播者，用隔离和社交距离来防止他们的密切接触者受到大剂量病毒暴露。Identification of symptomatic or asymptomatic high virus spreaders by quantitativePCR or new rapid tests based on viral protein detection in saliva or nasopharyngealswabs to promote their quarantine and social distancing to prevent high doseexposure of highly susceptible contacts 10.2.2 所有人都要避免累积大剂量病毒暴露。Cumulative high dose exposure should be prevented for everybody; however, in thisphase in which many governments are pursuing herd immunity, even youngindividuals who may have low levels of natural antibodies should be not exposed tothe virus, especially if shed at moderate/high doses 10.2.3 为了避免大剂量病毒暴露（注意这里没有累积二字），媒体应该宣传勤洗手，佩戴医用口罩，社交距离，避免摸脸，以及宣传用设备追踪的好处。（有趣的是这里说是医用口罩）To prevent high dose exposure information campaigns should be implemented topromote the attention to fomites in addition to hand washings, medical maskswearing, social distancing and avoid touching eyes, nose and mouth and thepromotion of technical devices for contact tracing 10.2.4 抗体检测Glycan microarrays should be used in the attempt identifying profiles of naturalantibodies associated with milder COVID-19 disease evolution 10.2.5 防止病毒在感染早期快速渗透到肺部。在感染早期要避免吸烟和疲劳密集的活动，例如高肺活量的体育运动。 这是为了防止在未启动适应性免疫应答的阶段，病毒绕过口腔和上呼吸道的自然免疫反应，从鼻，口腔和咽部粘膜大量突破进入到下呼吸道。 SARS-COV-2的直径为100 nm，并且包含它的气溶胶不仅可以沉积在气管支气管中，而且可以沉积在静止的肺泡区域中。后者可能会在呼吸非常大时增加，例如在马拉松或足球比赛中。特别是在较小的气道中，颗粒的沉积与吸气流量成反比。Prevention of viral faster penetration in the lungs during early stages of infection.Smoking, as well as activities, like intensive fatiguing work, including sport that implyhigh respiratory volumes should be avoided during the early stage of infection toprevent bypass of the natural immune response in the oral cavity and upperrespiratory airways and facilitate penetration of excessive amount of SARS-CoV-2from the nasal, oral and pharynx mucosa to the lower airways at a stage in which anadaptive immune response is still not initiated. SARS-COV-2 diameter is 100 nm, andaerosols containing it can deposit not only in the tracheobronchial, but also inalveolar regions at rest. The latter probably increases while breathing at very highvolumes, like during a marathon or a football soccer game. Especially in the smallerairways, the deposition of particles is inversely proportional to the inspiratory flow. 10.2.6 进行疲劳运动的运动员应采取特殊的预防措施。原因是如果运动员无症状感染，他们跑步时或咳嗽时会呼出一些亚纳米大小的含有病毒的气溶胶颗粒。这些飞沫或气溶胶会被（自己）再吸进去，导致病毒从上呼吸道传播到了下呼吸道。此外在团体运动或马拉松比赛这样的体育运动中，许多运动员密切接触，病毒颗粒很容易被其他运动员吸入，从而促进了病毒传播。 要强调指出，剧烈运动会导致分泌物吐出更加频繁，这可能进一步加重病毒在环境中传播，特别是如果不严格遵循疏远建议的话。Particular precautions should be given to athletes performing fatiguing sports, sincea portion of sub-micrometer-size, aerosolized particles, are expired by the runner oreliminated by cough or nasal secretions and may contain viruses if the athlete is anasymptomatic but SARS-CoV2 infected individual. These droplets or aerosol might bere-inhaled and facilitate the spread of the virus from the upper to the lower airways.Moreover, in sports were many athletes are in close contact, such as team sports ormarathons, the same particles have high chances to be inhaled by other athletes,facilitating viral transmission. To emphasize that strenuous exercise induces a muchmore frequent spitting of secretions and this can further contribute to theenvironmental SARS-CoV-2 spreading, particularly if the distancing recommendationsare not strictly followed.
后面就是一些医学建议了
其他的一些有趣的地方 模型提到了男性高危，和A型血风险略高的现象。并在6.1.2提到Natural IgM levels are lower in males and blood group “A” individuals。可能是原因。
The outcome of the COVID19 infection could already be defined in the first 10-15 days of infection and this may depend on viral exposure, immune weakness or intense physical exertion on incubation days. This was revealed by the first scientific model developed by three Italian researchers and described in the publication " The first, comprehensive immunological model of COVID-19: implications for prevention, diagnosis, and public health measures”Edited by Paolo Maria Matricardi (Charité Universitatsmedizin Berlin, Germany), Roberto Walter Dal Negro (National Center of Pharmacoeconomics and Pharmacoepidemiology - Verona - Italy) and Roberto Nisini (Immunology Department, Higher Institute of Health) and proposed for publication in the magazine Pediatric Allergy and Immunology, where it is currently under review, and published as a pre-print on the site.
According to the model, the outcome of the infection is decided in the first 2 weeks of the infection and depends on the balance between the cumulative dose of viral exposure and the effectiveness of the local innate immune response. The active components are the natural IgA and IgM antibodies (which are found in the saliva and in the secretions of the mucous membranes of the upper airways. The virus can overcome this first round if: innate immunity is weak, this condition occurs in many elderly people and in subjects without antibodies for genetic defects; the cumulative exposure to the virus is enormous, this situation occurs for example among doctors and health workers who have treated many serious patients without the appropriate protections; intense and / or prolonged physical exercise is performed, with very high respiratory flows and volumes, precisely in the incubation days immediately preceding the onset of the disease, thus facilitating the direct penetration of the virus into the lower airways and alveoli, greatly reducing the impact on the mucous membranes of the airways, covered by neutralizing antibodies. If SARS-CoV-2 overcomes the blockade of innate immunity and spreads from the upper airways to the alveoli already in the early stages of infection, experts explain, then it can replicate without local resistance, causing pneumonia and releasing high quantities of antigens. The subsequent adaptive immune response is delayed, intense with high affinity IgA, IgM and IgG antibodies, but not necessarily directed towards neutralizing antigens and, encountering large quantities of viruses in the meantime already replicated in many copies, causes severe inflammation and triggers cascades of mediators (complement, coagulation and cytokine storm) that lead to complications that often require intensive care and, in some patients, cause death. The model will help to better direct measures aimed at managing the second phase of the pandemic in our country and to stimulate translational and clinical research. In short, the three Italian researchers have elaborated, on the basis of the scientific evidence published to date, the first scientific model that explains in a coherent and unifying way the enormous diversity of the clinical manifestations of COVID-19, which vary from asymptomatic forms to death. The model itself is an important step forward in the fight against the virus, because it brings together all the pieces of a huge puzzle and offers doctors, researchers, administrators the first "navigator" to better navigate prevention, diagnosis, surveillance and public health measures. https://www.agi.it/salute/news/2020-04-24/coronavirus-iss-infezione-8432061/
回复 72楼梅干茶泡饭的帖子 我是读到这一段才产生疑问的“Moreover, in sports were many athletes are in close contact, such as team sports ormarathons, the same particles have high chances to be inhaled by other athletes,facilitating viral transmission. ”那一起跑的人也有可能会被感染，这样除了重症比例之外，光从总数上也应该有个明显的jump. 也许就像另一个楼里说的，都回hometown 不可追踪了？
我是读到这一段才产生疑问的“Moreover, in sports were many athletes are in close contact, such as team sports ormarathons, the same particles have high chances to be inhaled by other athletes,facilitating viral transmission. ”那一起跑的人也有可能会被感染，这样除了重症比例之外，光从总数上也应该有个明显的jump. 也许就像另一个楼里说的，都回hometown 不可追踪了？ aqbbcc 发表于 4/27/2020 7:32:12 AM
paper是英语的写的很通俗简明。个人观点，作者写的这么明白是给制定rule的人看的。我一会再po我自己的翻译。
这个理论现在还是pre-print。模型是三个意大利免疫/呼吸专家develop的，虽然都是意大利人，但是一作是在德国柏林，二作是在维罗纳的意大利呼吸专家有关于氧气疗法的著作，三作在罗马。我不认为是那种某个研究机构几个人凑一起灌水的东西。。。
意大利的不少媒体报道了这个模型。现在还在peer-review. 我读了之后觉得里面大多数“指导性”的东西，很易读。很多索引都是建立在从前的study,而不是新冠specific. 个人认为这只是指导模型。
客观来说欧洲大部分地区陆续进入phase 2，现在迫切需要指导模型，如果等来个实验测试。。。的确也晚了。。。
我觉得这个paper如果得到广泛认可，政府需要保护运动员和体力劳动者，复课地区的体育课也要受到影响。
看过我之前帖子的知道，自从意大利北部爆发之后，我就旗帜鲜明的反对滑雪，反对城市里运动达人跑步健身。所以我关注这个paper也有我的个人感情色彩。但是大家不妨自己去读一读，考虑下自己的风险。
-------下面是模型的理解讨论--------
个人理解：这个模型是从免疫的角度来指导phase 2里如何制定规范，如何在早期判断病人的风险的。最新颖的一个观点就是认为除了众所周知的免疫力低下（老人/基础病），大剂量暴露（医护等高危工作）这两条外，提出了潜伏期剧烈运动，或者长时间运动，是轻症迅速变重症的导火索。这样可以filter出来低危人群中的潜在重症患者。
众所周知，目前最大绊脚石就是那些较为健康年轻的人中究竟“谁会变成重症”。上海张医生主张的是轻症阶段的营养摄取是“轻转重”的决定因素。而这个意大利模型提出来的是“结局如何在感染初期就已经决定”。大量病毒是否在免疫建立前冲击肺泡是胜负手。
模型认为大部分低危感染人患者，病毒慢慢run the course, 免疫系统逐步建立，这样病毒发起总攻的时候，免疫已经“到位”。
年轻人中不少类似意大利1号患者的rapid转重症/危重插管的例子。（回顾：30+运动达人，潜伏期踢球马拉松，rapid转重症迅速危重插管，震惊欧洲）。模型认为其剧烈运动气喘吁吁导致的大量病毒从上呼吸道“冲”到下呼吸道，在免疫未“部署到位”前“总攻”肺泡，是rapid转重的原因。同时留给医生的window很小，极危险。
注意：免疫力，大剂量暴露，和潜伏期剧烈/长期运动是三个并列条件。模型认为任何一个就可以作为转重症的flag.
潜伏期剧烈运动指的是：健康年轻人处于感染后的潜伏期或症状极为轻微的时期。此时上呼吸道病毒大量复制时期。运动导致的深呼吸急促气流（俗称气喘吁吁，深呼吸）会把上呼吸道的病毒“冲”到下呼吸道，导致病毒冲破上呼吸道的天然屏障。病人此时还没有建立抗体机制，肺泡被突然的病毒洪流击垮，成为轻症转重症的关键因素。
这个模型认为轻症无症状 vs重症的决定因素是 “免疫量”和“病毒量”的大小关系，延伸为“大量病毒冲击肺泡”和“免疫保护建立”的时间点。如果冲击肺泡发生在免疫保护建立前就会导致重症(个人理解这里的重症指的是呼吸困难/肺炎）。
论文的abstract
The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19.
---------------论文关于剧烈运动的核心内容---------
4.4 - – Strenuous physical exercise 剧烈运动
两条
Strenuous exercise and IgA defect
Deep inhalation while performing strenuous exercise (running in particular) and virusspread to lower airways and alveoli
这一段的摘抄
4.4.1 Strenuous exercise and IgA
defectRegular, moderate exercise is associated with a reduction of the severity of acute respiratoryinfections [63], salivary IgA levels decline in athletes during and after a training season.[64]This observation may explain why elite athlete are at higher risk of upper airway infections.[65]A so-called ``open window'' of period is ranging between 3 and 72h hours after the strenuousexercise is finished.[66]
4.4.2 Deep inhalation while performing strenuous exercise (running in particular) and virusspread to lower airways and alveoliAerosols are considered an important mode of transmission for influenza.[67] Duringstrenuous exercise, requiring up to 40 l/min of respiratory flow, oronasal (combined nose andmouth) breathing dominates, with the oral component reaching up to 60% of the overallvolumes.[67] High flow air and change of breathing from nose to mouth breathing inducesprogressive cooling and drying of the respiratory tract mucous. Decreasing movement ofciliated cells and increasing mucosal viscosity, finally impairing filtering of microorganismsfrom the upper respiratory tract system.[68]The pattern of breathing during strenuous exercise changes dramatically by a tremendousincrease of ventilation (i.e.: inspiratory and expiratory volumes of air), and of alveolarventilation in particular. Obviously, these changes mostly attain to whatever kind of runnersbelonging to all sport disciplines, being semi-professional and professional athletesparticularly exposed (such as much more than individuals of common population) due to theirfrequent practice of extreme and long-lasting exercise. Furthermore, the majority of theseathletes have their lungs that usually work in perfect physiological conditions, such as veryclose to those of the “ideal lung”. In other words, in the absence of any anatomical orphysiological factor causing a significant unevenness in distribution of their alveolarventilation. Paradoxically, these pre-existing ideal conditions significantly favor the deepinhalation of several irritants, allergens, infectious agents. Even the SARS-CoV-2 can thenspread more easily to the deepest areas of the lungs (alveolar bronchioles and alveoli) during strenuous exercise, and there start its aggressive action. Not by chance, a great proportion ofprofessional football players claimed the occurrence of fever, dry cough and malaise (anddyspnea in some cases) immediately after, or a few hours following their last official match.
在后面关于“Triggers of the cascades leading to ARDS and respiratory failure" 俗称“重症的导火索”这一段里面 提出了模型的重要假说 这里面的关于IgA IgM IgG的观点现在很多地方都有提到（虽然我也不大理解）
An intriguingobservation is that ARDS symptoms start in coincidence with the onset of the SARS-CoV-2antibody specific immune response. Interestingly, the serum levels of specific IgA, IgM, andIgG are the highest in patients with the worst clinical course. [30,100] We may hypothesizethat in individuals in whom the virus early reaches the lung and actively replicates, a robustPreprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 24 April 2020 13adaptive immune response contributes to the tissue damage and severity of the pneumonia.This hypothesis may contribute to explain why patients with agammaglobulinemia had a mildpneumonia and recovered without experiencing complications requiring oxygen therapy.[101] Antibody may be simply a bystander consequence of a powerful viral replication, orrather the direct trigger of a severe inflammation.
值得注意的是这里特地提到了ADE 并没有rule it out.排除这个可能。
第九条是论文核心模型“ A model of the interaction between SARS-CoV-2 and immune system”
First stage (upper airways): viral clearance or pneumonia - 第一阶段上呼吸道感染。三个scenarios分别是“年轻健康人”“老人”“年轻但是大剂量暴露”
Second stage (pneumonia): recovering or complications. 第二阶段肺炎-这里是核心重点
If the virus reaches the alveoliwell after the establishment and expansion of a very efficient adaptive immuneresponse, the patient will probably never require oxygen and will not undergocomplications.By contrast, if the virus infects the alveoli early enough (i.e. already 7 days from theinfection or 2-3 from the first symptoms), the chances of a better replication in the lungare higher. When the specific response is established, massive amount of the virus caninteract with massive amounts of antibodies with high affinity.
如果病毒感染肺泡的时间点足够早（比如感染后7天，或者症状出现的2-3天），那么病毒在肺部大量复制的机会更高。 后面介绍了4种pathway，大量术语。
划重点：对诊断，公共卫生和临床干预的意义 Implications for diagnosis, public health and clinical intervention
-声明要小心谨慎，因为对于新冠的各种研究都是初步的不完全的-
如何预防重症 - Prevention of severe infections
10.2.1 通过定量PCR或快速测试来找出有症状或者无症状的高剂量病毒传播者，用隔离和社交距离来防止他们的密切接触者受到大剂量病毒暴露。Identification of symptomatic or asymptomatic high virus spreaders by quantitativePCR or new rapid tests based on viral protein detection in saliva or nasopharyngealswabs to promote their quarantine and social distancing to prevent high doseexposure of highly susceptible contacts
10.2.2 所有人都要避免累积大剂量病毒暴露。Cumulative high dose exposure should be prevented for everybody; however, in thisphase in which many governments are pursuing herd immunity, even youngindividuals who may have low levels of natural antibodies should be not exposed tothe virus, especially if shed at moderate/high doses
10.2.3 为了避免大剂量病毒暴露（注意这里没有累积二字），媒体应该宣传勤洗手，佩戴医用口罩，社交距离，避免摸脸，以及宣传用设备追踪的好处。（有趣的是这里说是医用口罩）To prevent high dose exposure information campaigns should be implemented topromote the attention to fomites in addition to hand washings, medical maskswearing, social distancing and avoid touching eyes, nose and mouth and thepromotion of technical devices for contact tracing
10.2.4 抗体检测Glycan microarrays should be used in the attempt identifying profiles of naturalantibodies associated with milder COVID-19 disease evolution
10.2.5 防止病毒在感染早期快速渗透到肺部。在感染早期要避免吸烟和疲劳密集的活动，例如高肺活量的体育运动。 这是为了防止在未启动适应性免疫应答的阶段，病毒绕过口腔和上呼吸道的自然免疫反应，从鼻，口腔和咽部粘膜大量突破进入到下呼吸道。 SARS-COV-2的直径为100 nm，并且包含它的气溶胶不仅可以沉积在气管支气管中，而且可以沉积在静止的肺泡区域中。后者可能会在呼吸非常大时增加，例如在马拉松或足球比赛中。特别是在较小的气道中，颗粒的沉积与吸气流量成反比。Prevention of viral faster penetration in the lungs during early stages of infection.Smoking, as well as activities, like intensive fatiguing work, including sport that implyhigh respiratory volumes should be avoided during the early stage of infection toprevent bypass of the natural immune response in the oral cavity and upperrespiratory airways and facilitate penetration of excessive amount of SARS-CoV-2from the nasal, oral and pharynx mucosa to the lower airways at a stage in which anadaptive immune response is still not initiated. SARS-COV-2 diameter is 100 nm, andaerosols containing it can deposit not only in the tracheobronchial, but also inalveolar regions at rest. The latter probably increases while breathing at very highvolumes, like during a marathon or a football soccer game. Especially in the smallerairways, the deposition of particles is inversely proportional to the inspiratory flow.
10.2.6 进行疲劳运动的运动员应采取特殊的预防措施。原因是如果运动员无症状感染，他们跑步时或咳嗽时会呼出一些亚纳米大小的含有病毒的气溶胶颗粒。这些飞沫或气溶胶会被（自己）再吸进去，导致病毒从上呼吸道传播到了下呼吸道。此外在团体运动或马拉松比赛这样的体育运动中，许多运动员密切接触，病毒颗粒很容易被其他运动员吸入，从而促进了病毒传播。 要强调指出，剧烈运动会导致分泌物吐出更加频繁，这可能进一步加重病毒在环境中传播，特别是如果不严格遵循疏远建议的话。Particular precautions should be given to athletes performing fatiguing sports, sincea portion of sub-micrometer-size, aerosolized particles, are expired by the runner oreliminated by cough or nasal secretions and may contain viruses if the athlete is anasymptomatic but SARS-CoV2 infected individual. These droplets or aerosol might bere-inhaled and facilitate the spread of the virus from the upper to the lower airways.Moreover, in sports were many athletes are in close contact, such as team sports ormarathons, the same particles have high chances to be inhaled by other athletes,facilitating viral transmission. To emphasize that strenuous exercise induces a muchmore frequent spitting of secretions and this can further contribute to theenvironmental SARS-CoV-2 spreading, particularly if the distancing recommendationsare not strictly followed.
后面就是一些医学建议了
其他的一些有趣的地方
模型提到了男性高危，和A型血风险略高的现象。并在6.1.2提到Natural IgM levels are lower in males and blood group “A” individuals。可能是原因。
很多人问什么算“剧烈运动”。这三个人都是意大利人。首先声明我没居住在意大利也不会说意大利语，只是经常去玩已经身边好几个意大利同事。
我对他们用词的理解是，他们把意大利语的词汇经常等同于英语书面词汇（拉丁文后遗症），所以说要仔细读，而且他们用词很容易有用得太严重的问题。
我读paper之后的理解，这里所谓的“剧烈”不是一般健身用来衡量强度的心跳，而是“呼吸气流”。
paper强调的是运动/体力活导致的大呼吸气流。中文俗称”气喘吁吁“，也包括特意的深呼吸（让我联想到瑜伽）。所以可以造成长时间或者剧烈的深呼吸/急促呼吸的运动是包含在里面的。
不过这个模型强调一个量的问题。潜伏期就算不锻炼，病毒也会在呼吸的时候少量跑到肺里面。
如果长时间剧烈运动，比如马拉松啥的，就会导致大剂量病毒冲击肺泡。所以我没看出来OOXX有啥要紧，除非时间特别长，当然某些小药丸我看是最好别吃了。。。
🔥 最新回帖
哈哈哈哈哈哈哈，这个度好难把握，一不留神就obese成高危人群了。
🛋️ 沙发板凳
这个理论模型是从免疫的角度来指导phase 2里如何制定规范，如何在早期判断病人的风险的。最新颖的一个观点就是认为除了众所周知的免疫力低下（老人/基础病），大剂量暴露（医护等高危工作）这两条外，提出了潜伏期剧烈运动，或者长时间运动，是轻症迅速变重症的导火索。这样可以filter出来低危人群中的潜在重症患者。
这里是一个意大利媒体的报道 summary比我清晰
The outcome of the COVID19 infection could already be defined in the first 10-15 days of infection and this may depend on viral exposure, immune weakness or intense physical exertion on incubation days. This was revealed by the first scientific model developed by three Italian researchers and described in the publication " The first, comprehensive immunological model of COVID-19: implications for prevention, diagnosis, and public health measures”Edited by Paolo Maria Matricardi (Charité Universitatsmedizin Berlin, Germany), Roberto Walter Dal Negro (National Center of Pharmacoeconomics and Pharmacoepidemiology - Verona - Italy) and Roberto Nisini (Immunology Department, Higher Institute of Health) and proposed for publication in the magazine Pediatric Allergy and Immunology, where it is currently under review, and published as a pre-print on the site.
According to the model, the outcome of the infection is decided in the first 2 weeks of the infection and depends on the balance between the cumulative dose of viral exposure and the effectiveness of the local innate immune response. The active components are the natural IgA and IgM antibodies (which are found in the saliva and in the secretions of the mucous membranes of the upper airways. The virus can overcome this first round if: innate immunity is weak, this condition occurs in many elderly people and in subjects without antibodies for genetic defects; the cumulative exposure to the virus is enormous, this situation occurs for example among doctors and health workers who have treated many serious patients without the appropriate protections; intense and / or prolonged physical exercise is performed, with very high respiratory flows and volumes, precisely in the incubation days immediately preceding the onset of the disease, thus facilitating the direct penetration of the virus into the lower airways and alveoli, greatly reducing the impact on the mucous membranes of the airways, covered by neutralizing antibodies. If SARS-CoV-2 overcomes the blockade of innate immunity and spreads from the upper airways to the alveoli already in the early stages of infection, experts explain, then it can replicate without local resistance, causing pneumonia and releasing high quantities of antigens. The subsequent adaptive immune response is delayed, intense with high affinity IgA, IgM and IgG antibodies, but not necessarily directed towards neutralizing antigens and, encountering large quantities of viruses in the meantime already replicated in many copies, causes severe inflammation and triggers cascades of mediators (complement, coagulation and cytokine storm) that lead to complications that often require intensive care and, in some patients, cause death. The model will help to better direct measures aimed at managing the second phase of the pandemic in our country and to stimulate translational and clinical research. In short, the three Italian researchers have elaborated, on the basis of the scientific evidence published to date, the first scientific model that explains in a coherent and unifying way the enormous diversity of the clinical manifestations of COVID-19, which vary from asymptomatic forms to death. The model itself is an important step forward in the fight against the virus, because it brings together all the pieces of a huge puzzle and offers doctors, researchers, administrators the first "navigator" to better navigate prevention, diagnosis, surveillance and public health measures.
https://www.agi.it/salute/news/2020-04-24/coronavirus-iss-infezione-8432061/
这么说可以天天躺着吃吃喝喝没压力了
我慢慢post 华人网现在不知道咋的总是闪 我一口气粘贴太多容易没了 这个理论是说年轻低风险的人里面轻症变成重症是因为潜伏期剧烈运动。或者体力活。
等下我post细节 注意不是导致”感染“ 已经是潜伏期，就肯定是感染了。这个模型是说剧烈运动会导致rapid重症。不是必然的，就是风险高。
如果不是潜伏期。。。其实普通人运动还是可以提高免疫力的。这是个要合理控制的问题。
注意运动频率，避免不必要的运动
这就难办了。xxoo算不算剧烈运动啊？
啊，我几乎每天天黑之后在外面跑步，是不是也不能去跑了？
把爱渐渐放下会走更远
这个模型说的是病毒已经大量复制，然后剧烈运动导致本来要几天时间才能大量到达肺泡的病毒，借着气喘吁吁的“东风”快速到达肺泡。成为健康年轻人rapid重症的导火索。
指导意义就是 pre-screen健康年轻人的时候可以将潜伏期剧烈运动作为red flag.
但是，谁又能保证自己不是在潜伏期呢？连核酸检测几次都有不准的时候。保险起见，还是不要剧烈运动好了。
不够准确 我理解上呼吸道像一个沼泽 病毒在潜伏期大量繁殖但是被trap在上呼吸道沼泽中，能”游“到肺泡的量不大。然而如果长时间剧烈运动，就等于开闸放洪，大量病毒一起”冲“到肺泡，就重症威胁生命了。
这个和新冠上呼吸道少痰干咳的症状是吻合的。其实普通感冒的时候痰适量增加，吐痰是保护肺脏的。这次新冠不知道为什么无痰干咳，更危险。
“呼吸道分泌少量的粘液是正常的，它对人可以起一个保护作用。当人吸入比较冷和干燥的空气时，通过呼吸道可以使进入肺内的含氧空气进行湿润和加温，也可以使吸入空气中的尘埃、有毒的其他颗粒以及空气中的含细菌的尘埃颗粒吸附在湿润的支气管壁上，通过支气管上皮的纤毛运动，推向上呼吸道，通过咳嗽排出体外，起到了保护肺脏的作用”
老人院里的，身体本来就脆弱的不行了，不运动都是攻击目标，还需要运动吗？
make sense
这个运动量其实不大，不算剧烈运动。
还可以选用运动量小的体位。
老人院的符合第一条免疫力低下
90分钟的HIIT。。。是要出人命的节奏嘛。。。
哈哈哈
当然算，这么重要的事情，怎么现在才说
。。。几个mile还不剧烈？
仔细读题 是要求潜伏期的时候剧烈运动的这个人才有重症风险 所以是这个人危险大 应该统计下参加马拉松的后来有症状的轻症重症比例
LA一个county占了整个加州一半的病例。而且马拉松的运动员来自各地，即使感染，也是回去霍霍自己hometown了
LA马拉松我的确不清楚
意大利当时patient1参加马拉松的地方的确成为了重灾区 但是是否是因果关系就不好说了 因为patient1不仅跑去参加了马拉松，也肯定在当地逗留了。
patient1当时的活动范围除了伦巴底家附近，还去了热内亚所在的Liguria大区那附近的一个海边town参加马拉松。最初爆发的时候很明显那个地方领先附近town。
其实我个人怀疑LA不明显的原因是因为LA本身是人口密度大城市，传播的influence 在人口密集的基础上impact不大，就看不出来了。不过这只是我的个人理解。
我也有这个疑问 这里的重症我觉得指的是发展到了肺炎
职业运动员感染的听说不少 不知道多少发展到了肺炎阶段
健身达人这个水平进ICU 插管的报道还是很多的
哈哈。做饭还得做的。
这里说的是会不会变成重症 差不多是肺炎这个意思
肺炎之后会不会死就要看运气+身体底子了吧
其实欧洲这边看ICU里面的中青年健壮的还是真的比例很高的 高的可怕
当然这也有老人有的连ICU门都摸不到 或者进去了很快就挂了的因素在里面
我今年的健身房membership算是浪费了，即使reopen了也不敢去，室内通风不好，人多又都气喘吁吁汗流浃背的。
不过看NBA的情况，好多球员检测阳性，但是完全没有症状就好了，估计抵抗力强是重要因素。但是以前还看到另一种说法，就是免疫系统抵抗力强可能会引起炎症风暴。这个病毒太诡异了。
就是躺在那不动靠喝肥宅快乐水活下去
你们健身房没退款么？我是月收费的那种 lockdown开始的时候就自动所有人变成freezing 状态 一个月5块钱
其实挺聪明的 与其等会员来要全部取消 还不如freezing这样也就五块钱。。。懒得打电话了。。。。