TWiV 641: COVID-19 with Dr. Anthony Fauci

TWiV 641：安东尼·福奇博士谈新冠病毒 在这场访谈中，安东尼·福奇博士与病毒学家文森特·拉卡尼洛（Vincent Racaniello）和里奇·康迪特（Rich Condit）共同分析了SARS-CoV-2的机制现实。福奇博士强调，尽管呼吸道飞沫仍是主要传播途径，但无症状传播和潜在的气溶胶传播也发挥了重要作用。他讨论了利用PCR循环阈值（Ct ≥ 35）来指征无传染性的残留RNA，主张务实地开展快速抗原检测，并警告鉴于该病毒估计约1%的感染死亡率，切勿追求自然群体免疫。福奇博士还解释了ACTIV伙伴关系与“曲率极速行动”（Operation Warp Speed）的区别，概述了在承担“财务风险”的情况下生产疫苗如何在不牺牲临床安全标准的前提下实现快速部署。节目最后呼吁联邦对基础病毒学和原型病原体研究进行持续投资，以为未来的大流行做好准备。 RT-PCR检测中循环阈值（Ct）达到35或更高表明，分离出具有复制能力的SARS-CoV-2的概率极小，代表的是无活性的残留病毒遗传物质，而非具有传染性的活病毒。 (3:50) 封闭空间内的大规模暴发（例如“西奥多·罗斯福”号航空母舰上约有1000名水兵感染新冠）表明，无症状和症状前传播是病毒传播的主要驱动因素。 (5:47) 2020年年中美国全国血清阳性率仍处于约3%至4%的低水平，鉴于高发病率和死亡率，在没有疫苗的情况下寻求自然群体免疫是一种不可接受的策略。 (16:07) “曲率极速行动”在临床试验期间决定承担“财务风险”提前生产疫苗剂量，旨在压缩交付时间，目标是在2021年初准备好数千万至数亿剂可部署的疫苗。 (27:57)

In a July 2020 interview on This Week in Virology, NIAID Director Dr. Anthony Fauci evaluated the epidemiological dynamics of SARS-CoV-2 and outlined the scientific strategy guiding federal countermeasures. He emphasized that controlling the pandemic relies on pragmatic diagnostics, rapid outpatient therapeutics, and unprecedented vaccine manufacturing at financial risk rather than relying on natural herd immunity. Transmission Routes and Diagnostic Viability (0:00) Dr. Fauci assessed that large respiratory droplets remain the primary transmission pathway for SARS-CoV-2, although aerosol spread occurs under certain conditions, comparable to the 2003 SARS-CoV-1 Metropole Hotel outbreak in Hong Kong. While studies from NIAID's Rocky Mountain Laboratories detected viral RNA on non-porous surfaces like plastic and steel for 48 to 72 hours, finding RNA does not demonstrate replication-competent virus. Direct droplet transmission in crowded environments remains the chief concern, supporting universal masking. Regarding molecular diagnostics, Fauci highlighted that RT-PCR cycle threshold (Ct) values of 35 or higher signify a minuscule probability of culturing infectious virus, representing non-viable nucleotide fragments. He favored adopting rapid, low-cost antigen tests for high-frequency screening even if their analytical sensitivity is lower than PCR, arguing that catching individuals harboring transmissible viral loads effectively curtails community spread. Silent Spread, Schools, and Natural Herd Immunity (5:47) Citing the outbreak aboard the aircraft carrier USS Theodore Roosevelt—where roughly 1,000 sailors contracted the virus after a few initial symptomatic cases—Dr. Fauci concluded that asymptomatic and pre-symptomatic transmission drive a substantial portion of community spread. For pediatric populations, where data regarding transmission efficiency remained sparse, the NIH initiated the HERO study across 6,000 children and 2,000 families to quantify household attack rates and immune responses. Fauci recommended that school reopening decisions reflect local community transmission rates rather than a blanket federal policy, balancing children's welfare with mitigation measures such as masking and split shifts. Estimating the overall infection fatality rate at roughly 1%—lower than SARS-CoV-1 (~10%) and MERS-CoV (~37%), but considerably deadlier than seasonal influenza—Fauci dismissed achieving natural herd immunity through wild virus spread. With mid-2020 national seroprevalence at only 3% to 4% despite localized hot spots like New York City reaching 22%, relying on natural infection would yield catastrophic morbidity and mortality. Immunology, Spike Targets, and Durability (17:35) Drawing parallels to endemic seasonal coronaviruses where reinfection occurs within six to twelve months, Dr. Fauci anticipated that initial humoral protection against SARS-CoV-2 might also wane over time. However, he maintained that waning antibody titers can be addressed through booster regimens. Early Phase 1 data from Moderna's mRNA-1273 vaccine trial demonstrated that a 100-microgram dose elicited neutralizing antibody titers comparable to or exceeding convalescent serum. Addressing candidate vaccine design, Dr. Fauci defended focusing primarily on the surface spike protein to block its receptor-binding domain from binding human ACE2 receptors. He hypothesized that the mucosal, upper-respiratory nature of mild infections may inherently induce shorter immune memory than systemic viral dissemination, pointing to lifelong immunity seen in systemic pathogens like measles and smallpox. Resolving this requires comparative longitudinal studies and autopsy data to verify whether multi-organ pathology reflects direct systemic infection or secondary inflammatory sequelae. Harmonizing Countermeasures and Accelerated Manufacturing (24:52) Dr. Fauci differentiated the strategic roles of ACTIV and Operation Warp Speed (OWS). ACTIV serves as a scientific partnership prioritizing therapeutic targets, with an emphasis on early outpatient treatments—such as monoclonal antibodies, convalescent plasma, and direct-acting antivirals—to avert hospitalizations, while reserving dexamethasone and remdesivir for severe inpatient disease. OWS functions operationally to harmonize trial endpoints, immunological assays, and independent Data and Safety Monitoring Boards across disparate commercial developers. To compress vaccine development timelines from traditional multi-year schedules into months, the federal government underwrote the financial risk of scaling manufacturing plants and producing tens of millions of doses during Phase 3 trials before efficacy was proven. Fauci stressed that this compression incurred purely financial risk rather than safety compromises, aiming to make tens to hundreds of millions of doses available by early 2021. Long-term control of SARS-CoV-2 and defense against future emerging respiratory threats depend on sustained extramural funding for platform technologies and prototype pathogen research. Key unresolved biological questions remain, including the precise durability of natural and vaccine-mediated immunity, the real-world contribution of fine aerosols, and whether severe multi-organ complications stem from direct viral invasion or systemic inflammation.

美国国家过敏和传染病研究所（NIAID）所长Anthony Fauci博士在《This Week in Virology》节目中指出，阻断新冠病毒大流行的核心在于科学化干预与务实的公卫策略，必须通过疫苗构建免疫屏障，而非放任自然感染以求群体免疫。 传播途径、无症状扩散与Ct值临床意义 (0:00) 针对SARS-CoV-2的传播机制，Fauci博士评估认为飞沫传播仍是绝大多数感染的主要驱动力，保持6英尺社交距离和佩戴口罩至关重要；尽管2003年香港淘大花园（注：节目中提及Metropole酒店案例）证实了冠状病毒的气溶胶传播能力，但目前气溶胶在新冠中的贡献比例仍不明确。物表传播方面，NIAID落基山实验室研究显示病毒RNA可在钢和塑料等非多孔表面存留48至72小时，但检出RNA并不等同于具有复制能力的活病毒。关于无症状感染，Fauci以罗斯福号航空母舰（USS Theodore Roosevelt）暴发事件为例，指出数千名感染者不可能仅由极少数有症状者直接传染，证明无症状与前症状传播占据相当大的传播比重。 在核酸检测指标上，许多康复患者数周内持续出现PCR阳性，但BSL-3实验室往往无法分离出活病毒。Fauci明确提出当前临床研究正形成共识：当循环阈值（Ct值）达到35或更高时，分离出具复制能力病毒的概率极小，此时检测到的仅是无活性的残存核苷酸碎片。虽然常规报告仅提供定性结果，但仪器记录了原始Ct数值，医生有权调取以指导出院或转出决策。 儿童传播盲区、学校复课与快速抗原检测 (7:06) 谈及2020年秋季学校复课争议，Fauci将儿童传播风险归为“缺乏数据区”。尽管儿童重症率较低，但其感染率与续发传播能力尚不清晰。为此，美国国立卫生研究院（NIH）于2020年5月启动HERO研究，追踪2000个家庭的6000名儿童以获取血清学与传播数据。Fauci主张将复课作为基准目标，以避免长期停课对儿童发展及家庭造成的负面影响；但他反对全国“一刀切”，强调必须结合当地疫情发病率，推行错峰上下学、轮班制和强制口罩等差异化防护措施，同时优先保障教师与高风险人群的安全。 在筛查策略上，针对哈佛大学Michael Mina等人倡导的低成本每日唾液抗原检测，Fauci对这类快速检测策略表示认同。他指出，尽管抗原测试的分析敏感性低于RT-PCR，但PCR由于过于灵敏常在患者已无传染性时仍报阳性。快速抗原检测若能在集会、课堂或工厂开工前即时排查出高病毒载量感染者，将极大降低社区传播，监管与应用层面应坚持“不要让完美成为良善的敌人”。 全身性感染疑虑、致死率与自然群体免疫谬论 (13:23) 针对新冠是否引发系统性病变，Fauci倾向于认为病毒可能突破了呼吸道限制，但多器官衰竭究竟是直接病毒侵袭还是呼吸衰竭导致的下游继发炎症，仍需依赖严格的解剖病理学证据，例如在血管内皮、肾脏、肝脏或脑组织中寻找完整病毒颗粒。在感染致死率（IFR）方面，Fauci重申其在《新英格兰医学杂志》上的估计，即IFR约为1%，远高于季节性流感，但显著低于SARS（约10%）和MERS（约37%）。由于无症状感染者构成了庞大分母，大流行的总死亡人数由极高感染基数与相对温和的致死率共同决定。 针对部分群体提出的“自然群体免疫”策略，Fauci出示数据指出，截至2020年7月，除纽约市等严重疫情震中血清阳性率达到约22%外，美国全国平均感染率仅在3%至4%之间。若放任野生病毒自由传播以达到群体免疫所需的感染门槛，将带来无法承受的重症与死亡代价，因此必须依托疫苗而非放任感染来建立群体保护。 免疫保护期评估、刺突蛋白靶点与疫苗研发机制 (17:35) 关于免疫保护持久性，Fauci指出引起普通感冒的四种季节性冠状病毒免疫保护期通常仅维持6个月至1年，再感染十分常见。他推测纯呼吸道黏膜感染所诱导的免疫记忆通常弱于系统性感染，因此需要对比轻症与ICU重症患者的长期免疫差异。针对Moderna的mRNA-1273疫苗Phase 1临床数据，100微克剂量在45名受试者中诱导的中和抗体滴度已达到或超过康复者血清水平，即使抗体随时间衰减，也可通过补打加强针应对。 围绕疫苗抗原设计，Vincent Racaniello质疑是否应单一聚焦于刺突（Spike）蛋白。Fauci解释称，中和抗体阻断刺突蛋白受体结合域（RBD）与人体ACE2受体结合，是阻断病毒进入细胞最关键的保护关联物，尽管辅助性T细胞或抗其他结构蛋白抗体有一定作用，但主攻刺突蛋白是经典的结构免疫学路径。 ACTIV框架、曲率极速行动与“承担财务风险”生产 (24:52) Fauci厘清了公私合作项目ACTIV与“曲率极速行动”（OWS）的分工：ACTIV主要由政府机构与学术界组成，负责评定科研优先级；OWS则是执行协调机构，负责统一临床试验设计、共享数据和安全监查委员会（DSMB）及标准化终点指标。在治疗药物方面，鉴于地塞米松适用于需要氧气支持的重症晚期患者，瑞德西韦用于加速早期住院康复，ACTIV将攻关重点转向门诊早期干预手段，优先布局单克隆抗体、超免疫球蛋白、恢复期血浆和直接抗病毒药物，以期降低住院率。 面对研发过快的公众疑虑，Fauci回顾了从1月10日病毒基因组公布到62天后mRNA启动Phase 1临床、5个月后启动3万人Phase 3试验的前所未有历程。他澄清，所谓“承担风险制造”完全是政府在Phase 3结果出炉前投入数亿至数十亿美元预先建立产能，承担的是“财务风险”而非医学或安全风险；若临床成功，该策略可在2021年第一季度迅速交付数千万至数亿剂疫苗，抢回宝贵时间。 Fauci强调，应对新兴病原体需要国会持续性投入基础研究与平台技术储备，而非在危机过后削减经费。SARS-CoV-2的真实全貌仍有待长期随访解剖病理、多中心血清学及儿童传播数据给出最终裁决。

[5:47] Dr. Anthony Fauci: I can't imagine, Richard, that one symptomatic person coughed on a thousand people and infected them; it would almost have to be a substantial amount of asymptomatic carriage and transmission. [27:57] Dr. Anthony Fauci: I don't like the word Warp Speed, because it makes it look like you're carelessly rushing, but to to do things in the way we've done it right now is truly remarkable.

[0:00] this week in virology the podcast about [0:03] viruses the kind that make you [0:06] sick [0:07] [Music] [0:10] from microbetv this is twiv this week in [0:14] virology [0:16] 641 recorded on july 16th [0:20] 2020 i'm vincent raqueniello [0:23] and you're listening to the podcast all [0:25] about viruses [0:27] joining me today from austin texas rich [0:30] condit hi there vincent good to be here [0:34] and our very special guest today is the [0:37] director of the national institute of [0:39] allergy and infectious diseases dr [0:41] anthony fauci welcome back [0:44] thanks vincent nice to see you nice to [0:46] see you rich you were last on twitter [0:48] in 2013. boy have things have changed [0:52] huh [0:52] yeah a little bit so we wanted to ask [0:55] you [0:56] a bunch of science questions about [0:58] sarsko v2 and [1:00] kovid19 and we have we've put them in [1:04] little sections and this first section [1:05] is all about transmission and [1:07] and testing and i wonder if i could [1:09] start by asking what your thoughts are [1:12] on uh the relative contributions of [1:16] what we know are the three routes of [1:17] transmission droplets [1:19] aerosol and contact [1:23] you know you know i don't think it's in [1:25] events that there's really [1:26] firm firm data there's the assumption [1:29] that it's mostly droplets you know just [1:31] recently there's been a buzz [1:33] about the degree of aerosol and what [1:35] that really means [1:37] um there's it's almost impossible to be [1:40] able to determine [1:42] except when you have an event you might [1:45] recall very well the famous hotel in [1:47] hong kong with [1:48] sars where we had uh infections that [1:51] went up and down [1:52] vertically and across the courtyard to [1:55] the other hotel [1:56] i mean that's a surefire aerosol if [1:59] there ever was one but when you have [2:01] both droplet and regular aerosol [2:04] uh you know it's tough to distinguish [2:06] the two i would think [2:08] as an intelligent guess that it is [2:10] almost [2:12] a very large majority of it is the [2:14] standard [2:15] aerosol wears if you stay i mean the [2:17] standard droplet [2:18] which is if you stay six feet or more [2:20] away it's unlikely [2:22] that the droplet will reach you but i [2:24] would i would not [2:25] rule out the possibility that there is a [2:27] degree of aerosol the extent of which i [2:30] don't know [2:31] surfaces we know it can [2:34] stay on surfaces hard enameled steel [2:38] plastic more than corrugated cotton [2:41] material and things like that [2:43] you know a study that was done by [2:45] vincent munster from the rocky mountain [2:46] labs [2:47] showed about you know 48 to 72 hours on [2:51] surfaces but that's pcr-able we're not [2:53] so sure if it's [2:55] replication competent so that's another [2:57] thing that's kind of [2:58] up in the air yeah so no firm [3:00] information on what we're talking about [3:02] so do you have any [3:03] any feeling for like the relative [3:05] contribution of direct [3:07] droplet uh uh transmission [3:10] and surface mediated fomite mediated [3:15] you know i don't but if you look at the [3:17] circumstances [3:18] of when crowds are together you would [3:21] you would imagine it's mostly droplet [3:23] and i'm sure if somebody coughs into the [3:26] hand and opens the door if somebody [3:28] comes 15 minutes later [3:30] and opens the same door that it you know [3:32] it's a good chance [3:33] you're gonna get transmission but i [3:35] would think that it's again if you [3:37] compare [3:38] surface to droplet i would go with [3:40] droplet predominant [3:42] it seems to me this is important because [3:43] it speaks to the effectiveness of masks [3:46] right exactly exactly [3:50] all right there have been a number of [3:52] reports of patients who [3:54] shed viral rna for weeks as determined [3:57] by pcr [3:58] doesn't seem to be infectious virus and [4:01] the real question is are they a threat [4:02] for transmission and i'm wondering [4:04] if you think we could use a cut off of [4:08] viral loads determined by pcr to say [4:11] this patient [4:12] is no longer infectious can go home can [4:14] go to a nursing facility [4:16] because right now the the physicians are [4:18] really having a hard time with that [4:20] right again a good question and what is [4:23] now [4:24] sort of uh evolving into a bit of a [4:27] standard [4:28] that if you get a cycle threshold [4:32] of 35 or more that the chances of it [4:35] being replication competent are [4:37] minuscule [4:38] so that if somebody and you know we do [4:40] we have patients and it's very [4:41] frustrating [4:42] for the patients as well as for the [4:44] physicians [4:45] somebody comes in and they repeat [4:48] their pcr and it's like 37 [4:52] cycle threshold but you never if you [4:55] almost never can [4:56] culture virus from a 37 [4:59] threshold cycle so i think if somebody [5:02] does come in with 37 [5:03] 38 even 36 you got to say you know [5:07] it's just it's just dead nucleotides [5:09] period [5:10] yeah because as you know we can't easily [5:13] culture infectious viruses you don't [5:14] have a bso3 lab everywhere [5:16] exactly exactly okay so is the the [5:19] threshold cycle uh [5:23] uh is reporting that a pretty standard [5:25] practice and doing a diagnosis now [5:27] rather than just positive or negative [5:28] okay good yeah i mean if when you go in [5:32] when i get my test you know it's [5:34] negative when someone comes in and it's [5:35] positive [5:36] they don't give them the threshold until [5:39] you go back and ask for it [5:40] okay but they they've got it they've got [5:43] it [5:44] they've got it so uh [5:47] what's your current uh perspective on [5:50] the fraction of transmission now [5:54] that's either asymptomatic or [5:56] pre-symptomatic versus symptomatic [6:00] you know richard i know you're gonna [6:03] you asked that yeah i like these [6:06] questions because [6:08] there's no right or wrong answer because [6:09] we don't know [6:11] but we can guess so long as we don't [6:14] take our guesses too seriously [6:16] so you know i think it has to be [6:20] substantial uh if you combine [6:23] asymptomatic with pre-symptomatic i [6:26] think if you put them together [6:28] and you look at the circumstances in [6:31] which [6:32] it's spread you get individual [6:36] instances like what happened on the [6:38] teddy roosevelt [6:40] nuclear aircraft carrier where you had [6:43] a few symptomatic sailors and a thousand [6:46] sailors [6:47] got infected i can't imagine [6:50] richard that one symptomatic person [6:55] coughed on a thousand people and [6:57] infected them [6:58] it would almost have to be a substantial [7:00] amount of asymptomatic [7:02] carriage and transmission okay [7:06] so um this is a question [7:09] particularly relative to schools opening [7:11] i i see [7:13] stuff in the news that implies that some [7:15] people at least [7:16] think that children uh either acquire or [7:20] transmit [7:21] the virus somehow differently than [7:24] adults [7:24] and i'm wondering if there's really any [7:26] evidence for that [7:28] yeah good question i think that's one of [7:31] those data-free zones [7:32] i mean really i i don't think that there [7:36] is [7:36] conclusive evidence either way i mean [7:39] there is [7:40] it's out there that or certainly [7:42] children [7:43] don't get sick nearly as much as right [7:46] as adults the question is do they get [7:48] infected right [7:50] and if so do they transmit right as you [7:53] said that has really [7:54] important relevance to school opening [7:57] so the answer is we don't know [8:00] but what we're doing we have a study [8:02] that we started on may 1st [8:05] called the hero studies human [8:07] epidemiology and [8:08] and i forgot what the other things stand [8:10] for but it's going to be 6 [8:12] 000 people kids in 2000 [8:15] families looking at the rate of [8:17] infection [8:18] the transmissibility to parents and [8:21] family members [8:22] and whether or not they get sick and [8:23] what their antibody response is okay [8:25] good so we we should know the answer to [8:27] that question [8:28] soon as opposed to just guessing because [8:31] i think [8:32] my my uh impression is that in the [8:34] popular [8:36] media that the the uh [8:40] uh understanding that kids don't get [8:43] sick as much gets [8:44] sort of misinterpreted or extrapolated [8:46] to the school system to say well [8:48] since they aren't getting sick then [8:50] putting them together back in school is [8:51] not a problem and [8:52] i don't that's not a logical conclusion [8:56] from the fact they don't get sick right [8:57] you're right you're right [8:59] so so in line with that [9:02] you know on our podcast twiv we get lots [9:05] of email from [9:06] teachers who want to know what's the [9:09] safest way to open schools in the fall [9:11] and [9:11] so how can we do that in a safe way get [9:14] these kids back but [9:15] what do we have to do [9:19] you know vince it's it's really i think [9:23] it [9:24] to address that that that question i i [9:26] generally take in multiple steps so [9:28] just give me 30 seconds i'll go quickly [9:31] is that i think a fundamental principle [9:34] should be that to the best of your [9:36] capability [9:38] given the circumstances which i'll get [9:39] to in a second you should try and get [9:41] the kids back to school [9:43] because what we're seeing is that the [9:46] you know the the downstream uh [9:50] unintended um [9:53] deleterious consequences ripple effects [9:57] of kids not being in school for the kids [10:00] for the parents for society [10:02] can be substantial so if you make your [10:04] default [10:06] we're going to try and get the kids back [10:07] to school having said that [10:11] it varies greatly where you are [10:15] you know we we tend to sometimes think [10:17] of this [10:18] and when when foreign countries and and [10:21] our foreign colleagues [10:23] look at the united states they tend to [10:25] look at us as a uni-dimensional country [10:28] as you guys know it's a big country and [10:30] it's really different geographically [10:32] demographically [10:33] so there may be some counties where heck [10:37] send the kids back to school don't worry [10:38] about anything and then there are other [10:40] areas where there's enough infection [10:43] you gotta decide either it's not safe to [10:46] get the kids back to school or [10:48] if it is you've got to do things that [10:51] mitigate [10:52] risk and that could be alternate day [10:55] classes morning afternoon wearing masks [10:58] protecting the vulnerables it's not one [11:01] answer [11:02] to a question it depends on a number of [11:04] different circumstances [11:06] but the one thing that's critical is [11:08] that if you're that the first thing is [11:09] paramount you have to be [11:11] you have to be attentive to and [11:13] sensitive to [11:14] the safety and the welfare of the [11:16] children and the teachers [11:18] and the teachers the reason i say and [11:20] the teachers [11:21] because you could have the situation [11:23] where you decide you want to bring the [11:25] kids back [11:25] and the teachers don't want to come back [11:27] i mean i think that's a reality that [11:30] could happen [11:32] so we're seeing uh in austin we're [11:34] seeing uh [11:35] demonstrations from teachers saying hey [11:38] we're here too yeah yeah so [11:42] it seems to me that testing should be a [11:45] part of [11:45] uh getting back to school and yesterday [11:47] we spoke with [11:48] michael minna from the broad institute [11:51] who [11:51] is a champion of the idea of having a [11:54] one dollar daily saliva based [11:56] antigen test and he thinks it can be [12:00] done with our amazing manufacturing [12:02] capabilities have [12:03] you ever thought about that and uh is [12:05] that ever going to happen [12:07] well you know maybe not specifically [12:10] what he spoke about but something along [12:13] that line [12:15] is really what is needed is something [12:17] that you could essentially do as many [12:19] tests as you [12:20] want it's instantaneous you get the [12:21] answer bingo you're done i mean we [12:24] really do need that i mean it would [12:26] alleviate a lot of anxiety number one [12:29] and number two [12:30] it would be an important public health [12:32] tool i mean if you could do that [12:34] before you send a group together into a [12:36] class or a group together into a factory [12:39] to work [12:40] i mean how great would that be knowing [12:41] that at that given moment [12:43] everybody was negative right [12:46] yeah this game in our conversation [12:48] yesterday this came down to [12:50] uh sensitivity questions okay uh [12:54] because he's talking about uh tests that [12:56] uh generally are less sensitive than pcr [12:59] but he says they don't have to be that [13:00] sensitive the pcr [13:02] as we've already discussed in in in some [13:04] senses can be [13:05] too sensitive so if you can catch most [13:08] of the really high virus load with uh [13:11] even a test that's not as sensitive that [13:13] that may be sufficient to really [13:15] significantly mitigate absolutely as an [13:18] example of don't let the perfect be the [13:20] enemy of the good really yes interesting [13:23] so we've seen uh reports from here and [13:27] there about the [13:28] notion that the virus may cause a [13:32] systemic infection certainly there are [13:34] systemic sequelae [13:35] okay but there have been reports [13:38] occasionally [13:40] indicating that the virus itself may [13:42] cause at least a small viremia [13:44] or actually infect the vasculature [13:47] or the kidneys or even the brain and i'm [13:50] wondering about your [13:51] uh take on that situation whether it's [13:55] really [13:56] confined as a respiratory virus and [13:58] those uh [13:59] sequelae a secondary or whether the [14:03] virus is getting out [14:05] you know my sense richard is that the [14:07] virus is getting out [14:09] although we don't have you know [14:11] overwhelming proof that that's the case [14:13] that we may be seeing [14:15] downstream distal effects of things that [14:18] are essentially respiratory [14:20] but what we are going to i believe get [14:23] good data on [14:24] are autopsy studies so if you start [14:26] seeing virus in different organs [14:28] that answers your question right there i [14:31] mean if you do autopsies and you see [14:33] endothelium and kidneys that have virus [14:36] in it [14:36] or liver or brain that's it it's it's an [14:40] open and shut case [14:41] okay and we're we're awaiting those [14:43] sorts of studies is that we are [14:44] we are okay all right uh and what's your [14:48] current best guess as to an infection [14:51] fatality rate [14:52] you know in the very very beginning of [14:55] this i wrote a perspective in the new [14:57] england journal of medicine [14:58] and i figured it was somewhere about one [15:00] percent um [15:01] it's totally dependent on the number of [15:04] asymptomatic infections [15:06] you know it could be five times a [15:09] particular [15:10] level if you're not counting all the [15:12] asymptomatics [15:13] you know given just the ballpark back of [15:16] the envelope type [15:18] look at what goes on you know [15:21] it's got to be it's got to be you know [15:24] obviously [15:25] more than seasonal flu but it's it's not [15:29] like [15:29] sars which was 10 or like mares which is [15:33] 37 [15:34] it's got to be somewhere around 1 i [15:37] think that [15:37] that fools people you know there are two [15:40] things that determine [15:41] the ultimate impact of an outbreak a how [15:44] many people get infected and b [15:46] how many die so if you get a few people [15:49] get infected [15:50] you know with a with a very high death [15:52] rate not a lot of people [15:54] die but if you get a lot of people [15:56] infected [15:57] with a reasonably low death rate a lot [16:00] of people are going to die right [16:02] so you know it's tough to calculate [16:04] because of the asymptomatics [16:07] so uh and let's talk a little bit now [16:10] about [16:11] immunity and and vaccines what's your [16:14] best estimate for the cereal prevalence [16:18] uh in the u.s i know it's going to vary [16:20] depending on where we are but overall [16:22] where do you think we are well new [16:25] york's 22 percent [16:27] so right away you're you're leading the [16:31] pack [16:32] uh because they really suffered terribly [16:34] i feel so badly about that you know i [16:36] think it's probably a few percent [16:38] three four percent something like that [16:39] that's what i think it probably is [16:41] so we're way way far from herd immunity [16:44] uh so uh that raises the question [16:48] can uh hurt immunity actually be [16:51] achieved without a vaccine this spanish [16:53] study came out and one of the reactions [16:54] to that [16:55] was that uh uh it just [16:58] wasn't even going to happen you know [17:02] i got my feeling is rich that if if [17:06] if we want to get hurt immunity [17:10] purely on the basis of infection [17:12] excluding [17:13] vaccine an awful lot of people are going [17:16] to get sick [17:17] and boy do i not want to see that i [17:20] don't want to see herd immunity that we [17:21] get [17:22] because we had 70 percent of the people [17:24] got infected and a whole bunch of people [17:26] got really sick that's the reason why [17:29] i'm putting my stock and [17:30] you know getting that vaccine as quickly [17:32] as we possibly can [17:35] so uh along the same line and this [17:37] impacts on the notion of [17:39] hurt immunity and this is one that i'm [17:41] really [17:43] confused about is uh reports that [17:46] uh immunity wanes um [17:50] and i'm interested in your perspective [17:52] on [17:53] uh in what if you know [17:56] or your perspective on what fraction of [17:59] infections [18:00] that generate immunity [18:03] that immunity wanes how fast [18:06] and and whether or not reinfection [18:10] really occurs [18:11] at a significant rate and what the [18:14] consequences of reinfection are is it [18:16] milder [18:16] because you still have partial immunity [18:18] what's the story [18:20] that's a lot of questions but i know but [18:23] they're very much related so usually i [18:25] can't remember [18:27] when somebody gives me five questions [18:29] it's okay i'll remind you [18:30] no but i think i can now because they're [18:32] quite related [18:33] so you know when you look at the history [18:35] of coronaviruses the benign [18:37] coronaviruses [18:38] go back in the old papers in the [18:40] literature the [18:42] the four common cold coronaviruses [18:45] the immunity did not last that long you [18:47] know it was lasting you know six months [18:49] a year or so [18:50] and that's the reason why people think [18:52] you get reinfected with coronaviruses [18:55] so that's the answer to the first [18:56] question what percentage of people get [18:58] immunity i think a hundred percent get [19:00] immunity [19:00] i guess the question is what percentage [19:03] lasts a reasonable period of time [19:05] and the answer to that is we don't know [19:07] but the reason we don't know for this [19:09] coronavirus [19:10] is that we're only six months into the [19:12] whole process [19:13] so if you really want to get a good [19:15] landscape view of what it is you got to [19:17] get wait a year or two and see [19:19] what happens answer your second question [19:21] the third question [19:23] is is it possible then if your immunity [19:26] wanes that you get re-infected [19:28] of course the question is if you get [19:31] re-infected [19:32] do you have a sub-optimal immunity [19:35] that then causes enhancement which is [19:38] what you're asking [19:39] i think buried in your question does it [19:42] make it better or does it make it worse [19:44] i don't think there was any any evidence [19:46] though i'm not sure people [19:48] looked in the common cold coronaviruses [19:51] if people get infected a second time [19:54] with the coronavirus do they get a worse [19:56] cold as it were so i don't know the [19:59] answer to that so that that's a big [20:00] unknown [20:01] i'm kind of hoping this is a i'm kind of [20:04] hoping that you [20:06] uh maintain some partial level of [20:08] immunity and actually get a milder [20:10] infection so [20:11] well i would hope so my goodness yeah [20:15] but no data no no like you say it's too [20:17] early [20:18] it's too early it's too early well you [20:20] know the [20:21] the current i environment does everyone [20:24] wants an answer yesterday right [20:27] yeah you know everyone wants an answer [20:29] you say i don't know they say well give [20:31] me a guess [20:31] yeah give them a guess they come back [20:33] they say you were wrong that's right [20:35] that's right so uh this notion of waning [20:38] immunity [20:39] that does that uh have any impact on [20:42] your perspective on how a vaccine might [20:44] work [20:45] not no not how it might work it's [20:48] whether you need to get boosted [20:50] okay yeah two or three i mean if you [20:52] look [20:53] we just not we but the group that did it [20:56] just published [20:57] my team but i'm not personally involved [21:00] in it [21:00] published two days ago in the new [21:02] england journal of medicine the phase [21:04] one data [21:05] and you know it really does look good i [21:07] mean you don't want to put all your [21:08] marbles in [21:09] 50 45 patients this is the moderna [21:12] vaccine right [21:13] yeah the mrna so if you look at the the [21:16] uh [21:16] the immune response in a moderate dose [21:19] 100 micrograms which was the moderate [21:21] dose [21:22] you get pretty robust neutralizing [21:26] antibody against [21:27] wild-type virus to the tune of as [21:30] high as or even higher than convalescent [21:33] serum [21:34] so at least for a finite period of time [21:38] guys [21:38] i think we're going to get a good [21:40] neutralizing response [21:42] how long it lasts we don't know [21:45] but you know i don't say this in a [21:47] flipping way i'll worry about that later [21:50] let me worry now about whether you can [21:52] get protection [21:53] over a season and if you can and the [21:56] immunity wanes then we'll worry about a [21:58] booster shot [22:01] so speaking of vaccines [22:02] [Music] [22:04] it seems to me that most not all but [22:07] most of them [22:08] are focused on the spike protein and we [22:11] talk about that a lot on [22:12] twiv and we'd love to get your [22:14] perspective do you think that's a good [22:16] idea to [22:17] not pay attention to all the other viral [22:19] proteins [22:22] it's a loaded question vince um [22:26] the answer is if you look at um [22:30] you know theoretically and conceptually [22:33] the neutralizing antibody that blocks [22:35] that binding to the ace ii [22:37] i mean classically that's the way you [22:40] block infection i don't [22:41] think that antibodies to other [22:45] uh components are unimportant [22:48] but i think that against the spike [22:50] binding site [22:51] is really i you know vince we had this [22:53] conversation years ago [22:55] about hemoglobin versus nuclear protein [22:58] versus neuraminidase with flu you know [23:01] and that's still a bit of an unanswered [23:02] question [23:03] even though you'd like to get it at the [23:05] hemoglobin i think the spike protein [23:07] antibody [23:08] it works it correlates with animal [23:10] protection so it all really looks pretty [23:12] good [23:13] although i do notice that one of your [23:16] warp speed candidates does have a few [23:19] other [23:20] viral proteins in there which is good [23:22] right yes yes so [23:23] do you know why immunity wanes [23:26] this speaks to the same question because [23:28] if if immunity wanes because the virus [23:31] tinkers with the immune system then [23:33] maybe that isn't an issue [23:35] for uh for a vaccine or or uh maybe it [23:38] maybe it is you know it gets back to [23:41] what you were saying about [23:43] viremia you know if this is truly [23:46] a respiratory borne infection i would [23:48] think that the immune response [23:50] would be weaker and would not last long [23:52] enough if you get somebody [23:54] you know what i would really like to see [23:55] and we'll get these data [23:58] you know as they evolve over the next [24:00] few months [24:01] i want to take somebody who gets [24:03] infected [24:04] gets up a respiratory infection a little [24:07] pulmonary [24:08] and then gets better versus somebody [24:11] that's in the hospital in an icu [24:13] with multi-system disease and find out [24:16] if the systemic descent dissemination of [24:18] the virus [24:20] really gives you immunity that that is [24:23] you know [24:23] years worth as opposed to months worth [24:26] that's okay [24:27] really interesting question okay so [24:28] track the track the [24:30] uh immunity relative to the sort of the [24:33] pathogenesis of their individual disease [24:35] that's interesting okay i i think that's [24:38] great idea because [24:39] you know the the viruses that give us [24:41] the best durable immunity are the ones [24:43] that are systemic like measles and polio [24:45] and i don't know maybe smallpox too [24:47] right rich [24:48] oh yeah i mean that's really durable [24:51] immunity [24:52] so uh tony what uh we have these uh [24:55] these things called warp speed and [24:57] active uh which are selecting vaccines [25:00] for [25:00] um upfront um payment and production [25:04] can you can you provide any insight as [25:07] to how these are [25:08] being selected or like what are the [25:10] criteria why are you why are you picking [25:11] them [25:13] so active is a [25:17] a public-private partnership of people [25:19] from different agencies of the [25:20] government as well as outside outside [25:22] investigators [25:24] who we bring together for the purpose of [25:27] doing just what you indicated of doing [25:29] prioritization [25:30] prioritization of agents prioritization [25:32] of studies [25:33] making sure that the resources are are [25:37] adequately and appropriately divided [25:39] among the different priorities [25:42] the operation warp speed is more of an [25:45] operational group that is looking at [25:49] diagnostics therapeutics and vaccines [25:51] predominantly focusing [25:53] right now on on therapeutics and [25:56] vaccines [25:57] to actually get involved in the the [26:01] conduct not that warp speed [26:04] conducts anything our group other groups [26:07] do it but to sort of outline [26:09] these are the protocols these are the [26:11] things that are going to match we've got [26:12] to harmonize the protocols [26:14] common database common dsmb [26:17] common immunological parameters common [26:19] primary and secondary endpoints [26:22] that all goes through warp speed more at [26:24] an operational way [26:26] whereas active is more of a think type [26:29] think tank type prioritization okay and [26:32] they're [26:33] obviously complementary functions then [26:35] and talking to each other [26:36] oh all the time yeah i mean they [26:39] intimated the boxes yeah they over the [26:40] boxes overlap a lot [26:42] yeah so active is [26:45] then participating in these decisions [26:47] about what the lead candidates are [26:49] absolutely absolutely and what are the [26:53] criteria [26:55] you know the criteria are what it looks [26:57] like [26:58] maybe in animal studies uh what the need [27:01] is [27:02] for the disease like for example i i'll [27:05] give you a good [27:06] a really good example so we have two [27:08] therapies now [27:10] that seem to work well in improving [27:12] either time to [27:14] discharge or mortality dexamethasone for [27:18] ventilated [27:19] people needing oxygen it's no good early [27:22] on [27:22] rem death severe better early on because [27:26] it's an antiviral [27:27] so what we really need right now are [27:30] agents [27:31] that operate early on that prevent a [27:34] sick person from going to the hospital [27:36] so [27:37] those are the ones we want to do so we [27:39] got convalescent plasma [27:40] hyperimmune globulin direct antivirals [27:44] monoclonal antibodies all those have [27:47] been prioritized and are all going into [27:49] clinical trials right now [27:51] that was on the basis which of all [27:54] deliberations about prioritizations [27:57] okay is it safe to say that in terms of [28:00] uh an an anti-viral approach a vaccine [28:04] therapeutic diagnostic there's never [28:05] been anything like this [28:07] oh for sure i mean this is you know i [28:10] don't like the word warp speed [28:12] because it makes it look like you're [28:13] carelessly rushing but [28:16] to to do things in the way we've done it [28:19] right now [28:20] is truly remarkable it's remarkable for [28:23] somebody like me who's been doing this [28:26] now [28:26] for 40 years and have been involved in [28:29] the development of a bunch of vaccines [28:31] back when we had a [28:32] you know get the the pathogen isolate it [28:36] grow it up then and doc inactivate it [28:39] attenuated [28:41] here you know the the the sequence came [28:44] out on the database [28:45] on january 10th i called a meeting in [28:48] this [28:50] room that we're in right now of our [28:52] people saying hey [28:53] let's go all hands on deck we got to [28:55] start developing vaccine the next day [28:58] we had a meeting by phone with moderna [29:01] put it into the mrna now we're on the [29:03] 15th of april [29:04] five days have gone by amazing 62 days [29:08] later [29:09] we were in a phase one trial and then [29:13] five months later we're gonna start a [29:14] phase three trial [29:16] at the end of july that's mind-boggling [29:19] guys i mean [29:20] that's that's orders of magnitude more [29:23] quickly than we were doing [29:24] a decade ago so uh a question we get a [29:28] lot [29:29] is uh uh [29:32] uh vaccine production and deployment i [29:35] mean even if we get a successful vaccine [29:38] are we going to be able to deploy it to [29:40] enough people soon enough what's [29:41] what's the horizon there no the horizon [29:45] is good richard because [29:46] what what we have is that we're doing [29:49] something at risk [29:50] not at risk to the patient not at risk [29:53] to the scientific integrity [29:55] but at risk to the money so what happens [29:58] is that the federal government has [30:00] invested [30:01] hundreds of millions of dollars per [30:04] candidate [30:05] and sometimes over a billion dollars [30:08] per candidate to have the companies [30:11] proceed at risk in other words instead [30:14] of [30:15] determining if you're successful here [30:17] then investing here [30:19] then determining if you're successful [30:20] here it's like you invest [30:23] right ahead you prepare the sites you do [30:25] everything [30:26] you start making doses even before you [30:28] know [30:29] that the vaccine works which means that [30:32] if it does work [30:33] you've saved many months if it doesn't [30:37] work [30:37] you've lost a lot of money so the [30:40] urgency of the situation [30:42] dictates that it's worth investing the [30:45] money [30:46] to save a lot of time so the companies [30:49] tell us [30:50] i can't promise you personally because [30:51] that's not what i do i can get you [30:53] the vaccine and i'll tell you if it [30:56] works [30:57] the companies will say that they will [30:59] have [31:00] enough vaccine by the first quarter of [31:04] 2021 [31:05] to be able to start distributing tens if [31:07] not hundreds of millions of doses [31:10] incredible yeah i mean with the modern [31:13] vaccine [31:14] i've been trying to get my head around [31:16] how much rna that is [31:18] yeah and how to make it really i know [31:22] it's tough are we good let's go we're [31:25] done [31:26] they're telling me we got one more [31:27] question because i gotta run to the next [31:29] okay [31:29] i have one more question then so we all [31:32] knew that [31:33] this in fact the last twit you were on [31:35] we said what do you [31:37] worry about at night and you said are we [31:39] ready for the next big one [31:41] and i would guess you're probably [31:43] thinking we weren't ready enough [31:44] but i'm wondering you know part of the [31:47] problem is that [31:48] in academia which is where we are we [31:50] can't work on viruses that aren't [31:52] circulating and infecting people it's [31:54] hard to get support for that [31:55] so do you see after this pandemic [31:59] a change maybe in the direction of niad [32:01] so [32:02] we could have extramural funding for [32:05] basic science on emerging pathogens that [32:08] are [32:08] a little bit too risky uh for the normal [32:11] funding procedure [32:13] you know vince you probably are aware [32:15] that we've already done that [32:16] even before covert 19. you know we had a [32:19] program [32:20] of prototype pathogens platform [32:22] technologies [32:23] and pre-selected microbes we put a fair [32:26] amount of money in it [32:27] so we've been doing that what i think is [32:29] going to happen now [32:30] we i think set the example to do that [32:33] now the congress realizes [32:35] that for the next one we've really got [32:37] to be prepared [32:38] so i am seeing i hope fingers crossed an [32:42] infusion of a lot of money [32:44] into this type of preparedness that [32:46] sounds great yeah [32:47] all right the last thing i want to say [32:49] uh dr fauci [32:51] is i want to thank you personally for [32:53] everything [32:54] that you have done and i i probably [32:56] speak for rich condit and many [32:58] uh of us virologists out there we're [33:00] we're 100 [33:01] 200 behind you and we look forward to [33:04] your leadership [33:05] for many years to come thank you for [33:08] joining us today dr fauci [33:10] yeah absolutely thank you appreciate it [33:12] always good to be with you guys [33:14] thank you thank you thanks so much they [33:16] say you too [33:17] well that is a fabulous twiv [33:21] 641 what do you think rich i just [33:25] i love that guy you know and i love [33:28] being able to talk to him like this as [33:30] i've [33:31] i i think uh you you see [33:34] the real tony fauci uh on this he's a [33:38] he's a scientist and he's a clinician he [33:41] cares about the science [33:43] he cares deeply about the science and he [33:45] cares deeply about the people [33:47] and about uh getting us done right and [33:49] he's not afraid to say [33:50] i don't know he's not afraid to say it's [33:53] a moving target [33:55] uh you know it's just a great person and [33:57] a great scientist and it's a privilege [33:59] to be able to spare [34:01] share some time with yeah we we really [34:03] appreciate [34:04] him taking the time to join us [34:07] i guess we are a bona fide thing and [34:11] wow of course he was on twit uh back in [34:14] 2013 as you heard uh yeah that's uh [34:16] actually [34:17] something you need to put in the show [34:19] notes or even up front in the show [34:21] but at least here that seven years ago [34:24] we spent a whole hour with him in his [34:26] office and that's [34:28] uh definitely worth listening to i [34:30] re-listen to it it gives his whole [34:31] history [34:32] um which is uh actually quite [34:34] interesting yeah the history of his [34:36] involvement with the [34:37] aids epidemic uh and winds up with that [34:41] ringer question what keeps you up at [34:43] night and it was [34:45] this the big one yeah i know i think [34:48] it's uh it's a it's an interview you [34:50] won't [34:51] find anywhere else basically so yeah [34:53] check [34:54] who does our interviews right uh this is [34:57] twiv [34:58] 641 you can find the show notes at dot [35:01] tv [35:02] slash twitter that will include the [35:03] links to [35:06] the old podcast send your questions and [35:08] comments it's with [35:09] microbe dot tv if you like what we do [35:12] consider supporting us microbe dot tv [35:15] slash contribute [35:17] our guest today of course from the [35:19] national institute of [35:20] allergy and infectious diseases was dr [35:23] anthony fauci [35:24] rich conditt rich conditt [35:27] is an emeritus professor university of [35:29] florida gainesville currently residing [35:32] in austin texas thank you rich you're [35:35] quite welcome i'll say it again it's a [35:37] privilege i'm [35:37] i feel very grateful for being able to [35:40] do this [35:41] bad for retirement right i'll tell you [35:43] retirement is [35:45] just rocks i never i never thought i [35:48] would do this much science in retirement [35:50] and it's some of them that's some of the [35:53] uh [35:54] best and most interesting science i've [35:55] ever done from my chair with a [35:58] headset on yeah we'll keep you busy [36:00] don't worry [36:01] great stuff great stuff i'm vincent [36:03] dracanello you can find me at [36:05] virology.blog i'd like to thank the [36:07] american society for [36:08] virology and the american society for [36:12] microbiology for their support of twiv [36:14] and ronald yankees [36:16] for the music this episode was recorded [36:19] edited and posted by me vincent [36:22] raqueniello [36:23] you've been listening to this week in [36:25] virology thanks for joining us we'll be [36:27] back [36:28] next week another twiv [36:31] is viral [36:42] [Music] [36:46] you