CORONAVIRUS DISEASE 2019 UPDATE (444): EARLY TREATMENT, HERD IMMUNITY, USA MOTORCYCLE RALLY, WHO, GLOBAL
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A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
In this update:
[1] Early treatment
[2] Herd immunity is not the answer
[3] USA (Sturgis, South Dakota): motorcycle rally [4] WHO: daily new cases reported (as of 18 Oct 2020) [5] Global update: Worldometer accessed 18 Oct 2020 22:37 EDT (GMT-4)
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[1] Early treatment
Date: Sat 17 Oct 2020 11:36 PM GMT+2
Source: Bloomberg [abridged, edited]
Hong Kong’s top pandemic doctor sees a way out of intensive care for thousands of COVID-19 patients: keeping them from entering in the 1st place. After sobering experiences 17 years ago with the outbreak of severe acute respiratory syndrome, Yuen Kwok-Yung is advocating early, aggressive hospitalization and treatment to minimize ravaging disease and death. Hong Kong’s 2% COVID-19 fatality rate as of Friday [16 Oct 2020], well below the global average, lends weight to the approach.
Most therapies for SARS-CoV-2 are authorized for use in severely ill patients, in some cases backed by research that’s still in question.
Yuen, the Henry Fok professor in infectious diseases at the University of Hong Kong for 15 years, is admitting patients with minimal disease so they can be isolated, monitored, and treated if needed. “In places like the UK and US, usually if you have mild symptoms, you are not admitted to a hospital at all — you just wait at home until you feel very bad or you have shortness of breath,” he explained over Zoom from his office. “But we basically admit any patients, even without symptoms, into the hospital for isolation.”
The strategy reduces transmission in the community, and enables patients to enter a clinical trial and receive experimental treatment soon after developing a fever or showing other signs of worsening illness, Yuen said. That’s critical because the amount of SARS-CoV-2 virus or “viral load” in patients peaks at around the time symptoms appear — similar to influenza.
Yuen recalls the trial and error involved in saving patients from SARS, also caused by a coronavirus. Soon after, he identified “a time bomb” of environmental and social conditions that he predicted would inevitably result in more deadly coronavirus outbreaks. That prediction came true in December [2019], when the 1st cases of a mysterious pneumonia came to light in Wuhan, in China’s Hubei province. Hong Kong responded to the novel coronavirus by preparing tests and advising citizens to wear masks.
Meantime, Yuen’s lab was conducting research that led to the 1st reported cluster among family members in which human-to-human transmission of the new coronavirus occurred. In February [2020], he joined the WHO-China Joint Mission to investigate the country’s early response and his lab has since reported a number of important findings, including the first confirmed SARS-CoV-2 reinfection.
Bitter lesson
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“All this is an extension of our experience in the year 2003,” Yuen said. “We have nothing to brag about because we learned bitterly from
2003 SARS.” The appearance of an unknown virus to which no one has immunity created a desperate need for effective treatments. Hong Kong doctors are using several experimental infusions including convalescent plasma — a mix of factors extracted from recovered patients’ blood — and interferon, an immune-system protein.
They’re also using the antivirals ribavirin and Kaletra, although preliminary results released Thursday [15 Oct 2020] from a World Health Organization-led trial involving 11 266 patients in 30 countries found they don’t decrease patients deaths [doi:
‘Modestly active’
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“We know that one drug is not good because all of these are very modestly active,” Yuen said. “We need early cocktail therapy to get good results.” Giving a combination of ribavirin, Kaletra, and interferon to patients in the 1st week of illness reduced the time to clear the virus by 6 days and shortened hospitalization by a week when compared with giving Kaletra alone, Yuen and colleagues showed in a study in May [2020]. The trial, published in The Lancet medical journal [
127 patients from [10 Feb 2020] to [20 Mar 2020] — more than half of the COVID-19 cases reported in Hong Kong during that period. Patients began treatment about 5 days after developing symptoms.
“With the memory of the 2003 SARS pandemic, most patients with
COVID-19 in Hong Kong accepted antiviral treatment, which explained our high recruitment rate,” Yuen and his team wrote. 16 years earlier, Yuen and many from the same group showed that a cocktail of ribavirin and Kaletra prevented serious illness and death in SARS patients [
Interferon response
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Evidence is mounting for early use of interferon in some patients.
Blockbuster studies published by the journal Science last month [September 2020] showed about 14% of critical COVID-19 patients have insufficient levels of the substance, which orchestrates defenses against viral pathogens. If the body mounts a good interferon response when the viral load is low, it can limit subsequent viral replication and prevent dangerous inflammation, Yuen said. A late or delayed interferon response to a high viral load, though, may trigger severe damage to the lungs. “This is really disastrous,” he said. That’s made injections of interferon the “backbone” of early treatments.
Some doctors outside Hong Kong agree with Yuen’s approach. Using antivirals early may suppress viral load and prevent the serious hyper-inflammatory response some patients develop in their second week of illness, said Richard Russell, a respiratory physician and senior clinical researcher in the Nuffield Department of Medicine at the University of Oxford, who is also conducting studies on COVID-19 patients.
Yuen’s strategy has pointed to how multiple existing antivirals may be repurposed and partnered with immune-modulating drugs as a bridge until protective vaccines become available, said Steven Opal, clinical professor of medicine at Brown University in Providence, Rhode Island.
Dexamethasone, a cheap, generic anti-inflammatory, was found in June [2020] [
Dexamethasone and Gilead Science Inc.’s remdesivir help patients with more advanced disease, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “The one thing we really need to do is get a bunch more interventions for early infection to prevent people from going on to needing hospitalization,” he said in an interview with the American Lung Association this month [October 2020]. Antibodies that are specifically designed to fight the coronavirus may also help, Fauci said. U.S. President Donald Trump credited Regeneron Pharmaceuticals Inc.’s antibody treatment with his recovery from infection.
Leprosy drug
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Yuen’s team is also investigating the potential of clofazimine, an inexpensive, 50-year-old antimicrobial that’s on the WHO’s list of essential medicines for leprosy. Studies in hamsters indicated it could fight SARS-CoV-2 and prevent infection [
Hong Kong took rapid and decisive action in response to COVID-19 because of the legacy of SARS, Yuen said. He hopes others will learn from the current crisis about the need to prepare for and mitigate the risks of future pandemics. “It’s the 2003 experience that allowed us to walk another mile early,” Yuen said. “I hope that everybody in the world will learn this time that emerging infectious disease is something that would happen more and more frequently.”
[Byline: Jason Gale]
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Communicated by:
Mary Marshall
[One of the challenges in interpreting the clinical trials does in fact deal with the timing of the intervention. Studies have indicated that in the early stages, one is dealing with the effects of the actual direct impact of the virus, whereas as time progresses, there is the impact of immune responses. Logically, administration of an antiviral when the deleterious effects of a hyperimmune response are the predominant clinical effects in a patient may not result in an impressive response to the antiviral agent. In turn, administration of dexamethasone during the early stages of an infection may suppress the normal immune response of the patient and result in more severe disease resulting from overwhelming viral loads.
Yuen’s comments are intriguing and definitely worthy of study as evidenced by the markedly reduced case fatality rate experienced in Hong Kong. – Mod.MPP]
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[2] Herd immunity is not the answer
Date: Sun 18 Oct 2020
Source: Washington Post [edited]
A half-million more people could die if America pursues a ‘herd immunity’ plan
As the COVID-19 pandemic continues in the United States and many parts of the world, millions of Americans are increasingly impatient for the economy and society to regain a more normal footing. [Some individuals] the Post reported last week, argue for “allowing the coronavirus to spread freely at ‘natural’ rates among healthy young people while keeping most aspects of the economy up and running.”
Their aim is to achieve “herd immunity,” the concept that if enough people are immune, those without immunity can be protected. Usually, this refers to immunity gained from vaccination; the goal of herd immunity has typically not been applied to a disease for which there is no vaccine.
There is a saying that for every complicated problem, a solution exists that is quick, simple — and wrong. That applies here: Pursuing herd immunity is the wrong, dead wrong, solution for the pandemic…
Less than 15 percent of Americans have been infected by the virus that causes COVID-19. If immunity among those who have been infected and survived is strong and long-lasting (and it may well be neither), and if herd immunity kicks in at 60 percent infection of the population (and it might be higher), with a fatality rate of 0.5 percent among those infected, then at least another half-million Americans — in addition to the 220 000 who have already died — would have to die for the country to achieve herd immunity. And that’s the best-case scenario. The number of deaths to get there could be twice as high.
The route to herd immunity would run through graveyards filled with Americans who did not have to die because what starts in young adults doesn’t stay in young adults. “Protecting the vulnerable,” however appealing it may sound, isn’t plausible if the virus is allowed to freely spread among younger people. We’ve seen this in families, communities, and entire regions of the country. First, come cases in young adults. Then the virus spreads to older adults and medically vulnerable people. Hospitalizations increase. And then deaths increase.
The vulnerable are not just a sliver of society. The 65-and-over population of the United States in 2018 was 52 million. As many as 60 percent of adults have a medical condition that increases their risk of death from COVID-19 — with many unaware of their condition, which can include undiagnosed kidney disease, diabetes, or cancer. The plain truth is that we cannot protect the vulnerable without protecting all of us.
A one-two punch is needed to knock out the virus — a combination approach, just as multiple drugs are used to treat infections such as HIV and tuberculosis. That in turn will allow the accelerated resumption of economic and social activity.
First, knock down the spread of the virus. The best way to do this is
— as the country has been trying to do, with uneven success — to reduce close contact with others, especially in crowded indoor spaces with poor ventilation. Increase adherence to the 3 W’s: wear a mask, watch your distance, and wash your hands (or use sanitizer). Where restrictions have been loosened, track early-warning triggers, and activate strategic closures to prevent an explosive spread.
Second, box the virus in to stop cases from becoming clusters and clusters from becoming outbreaks. Rapid testing should focus on those at greatest risk of having been exposed. The sooner people who are infectious get isolated, the fewer secondary cases there will be. That means rapid testing and rapid action when tests are positive. Close contacts need to be quarantined so that if they develop infection, the chain of transmission will stop with them.
A safe and effective vaccine may become available in the coming months
— or it may not. Yet even if it were widely administered (a big if), it wouldn’t end the pandemic. Even if a vaccine that’s 70 percent effective is taken by 70 percent of people — optimistic estimates — that leaves half of the population unprotected. For the foreseeable future, masks will be in, at least indoors, and handshakes will be out.
Although there’s no quick fix, this pandemic will end one day. In the interim, there are actions individuals, families, and communities across the country can take to reduce risk. The sooner the virus is under control, the quicker and more complete the recovery will be.
[Byline: Tom Frieden]
— [Herd immunity depends on the R0 of the virus or its reproduction number. That is the average number of people that a single individual infected with the virus can infect if those people aren’t already immune. The higher the R0, the more people need to be resistant to reach herd immunity. The R0 for COVID-19 is thought to be between 2 and 3. This means that one person can infect 2-3 other people. It also means 50% to 67% of the population would need to be resistant before herd immunity kicks in and the infection rates start to go down. However, because SARS-CoV-2 tends to be transmitted in clusters in high dispersion events, the theoretical R0 is only an average and not exactly accurate. As discussed in The Atlantic ( Therefore, herd immunity against SARS-CoV-2 is going to be difficult to achieve, except possibly with administration of a vaccine to the population, and perhaps even then additional control measures will be needed. In the meantime, masks and physical separation are the best approach to controlling the virus spread in the population. – Mod.LK] ****** It had been a long ride back from Sturgis, South Dakota, so when he 1st felt an ache at the back of his throat, KC figured he was just tired. He’d traveled the 400-some miles on his Harley, rumbling through wide-open farm and prairie land on his way home to Riverdale, Nebraska, where his girlfriend was waiting. A lifelong motorcycle enthusiast, the 50-year-old construction worker and father of 5 had been determined to go to the Sturgis Motorcycle Rally, a holy grail for bikers. Even when his girlfriend, AB, decided to stay back because she was worried about being around so many people during a pandemic, he was adamant about going. “I don’t think there was nothing that was going to stop me,” he said. Back home, KC took Tylenol for his throat and went to bed early. But he woke up the next morning coughing so hard he struggled to catch his breath. Over the next few days, the pain in his chest made him fear that his heart might stop, and a test later confirmed he had the novel coronavirus, which causes the disease COVID-19. He was admitted to the hospital 11 days later, on [27 Aug 2020]. Soon, his girlfriend and his sister were sick, and KC was going over everything he did and every place he visited in Sturgis, wondering where the virus had found him. Within weeks of the gathering, the Dakotas, along with Wyoming, Minnesota, and Montana, were leading the nation in new coronavirus infections per capita. The surge was especially pronounced in North and South Dakota, where cases and hospitalization rates continued their juggernaut rise into October [2020]. Experts say they will never be able to determine how many of those cases originated at the 10-day rally, given the failure of state and local health officials to identify and monitor attendees returning home, or to trace chains of transmission after people got sick. Some, however, believe the nearly More than 330 coronavirus cases and one death were directly linked to the rally as of mid-September [2020], according to a Washington Post survey of health departments in 23 states that provided information. In many ways, Sturgis is an object lesson in the patchwork US response to a virus that has proved remarkably adept at exploiting such gaps to become resurgent. While some states and localities banned even relatively small groups of people, others, like South Dakota, imposed no restrictions — in this case allowing the largest gathering of people in the United States and perhaps anywhere in the world amid the pandemic and creating huge vulnerabilities as tens of thousands of attendees traveled back home to every state in the nation. Many went unmasked to an event public health officials pleaded with them to skip, putting themselves and others at risk, because they were skeptical about the risks, or felt the entreaties infringed on their personal liberties. Rallygoers jammed bars, restaurants, tattoo parlors, and concert venues; South Dakota officials later identified 4 such businesses as sites of potential exposure after learning that infected people had visited them. Despite the concerns expressed by health experts ahead of the event, efforts to urge returnees to self-quarantine lacked enforcement clout and were largely unsuccessful, and the work by state and local officials to identify chains of transmission and stop them was inconsistent and uncoordinated. Those efforts became further complicated when some suspected of having the virus refused to be tested, said Kris Ehresmann, director of infectious disease epidemiology at the Minnesota Department of Health. Such challenges made it all but impossible to trace the infections attendees may have spread to others after they got home. Several infections tied to a wedding in Minnesota, for instance, “linked back to someone who had gone to Sturgis,” Ehresmann said. Those were not tallied with the Sturgis outbreak because “the web just gets too complicated,” she said. “When it comes to infectious diseases, it’s often the case that the weakest link in the chain is a risk to everybody,” said Josh Michaud, an epidemiologist and associate director for global health policy for the nonprofit Kaiser Family Foundation. “Holding a half-million-person rally in the midst of a pandemic is emblematic of a nation as a whole that maybe isn’t taking [the novel coronavirus] as seriously as we should.” The [7-16 Aug 2020] gathering has drawn intense interest from scientists and health officials, and will likely be studied for years to come because of its singularity. It’s not just that Sturgis went on after the pandemic sidelined almost everything else. It also drew people from across the country, all of them converging on one region, packing the small city’s Main Street and the bars and restaurants along it. And in contrast with participants in the Black Lives Matter protests this summer [2020], many Sturgis attendees spent time clustered indoors at bars, restaurants, and tattoo parlors, where experts say the virus is most likely to spread, especially among those without masks. Attendees came from every state, with just under half hailing from the Great Plains and substantial numbers journeying from as far as California, Illinois, and Arizona, according to an analysis by the Center for New Data, a nonprofit group that uses cellphone location data to tackle public issues. The analysis, shared with The Washington Post, shows just how intertwined the South Dakota rally was with the rest of the country — and how far the decisions of individual attendees could have ricocheted. KC feels certain he got the virus from his Sturgis trip and shared that with the contact tracer from the Two Rivers Public Health Department who phoned him after his case was recorded. Nebraska borders South Dakota, and health officials there expected they might see rally-related infections. Yet his illness was not classified as a Sturgis case, suggesting that even under the best of circumstances, infections might go uncounted. With so much still unknown, it worries him to think people might look at the rally and conclude that massive events aren’t concerning after all — that the risk is worth it. That was how he saw it before he got sick. He recalls having a fleeting thought as he guided his motorcycle through the turns of the famed Needles Highway 2 months ago, taking in the sweeping views and rock formations close enough to touch: “If I catch the virus and die, I will be a happy man. I have lived.” He hadn’t imagined that within a matter of days, he would feel that death was hovering right at his door. ‘No right decision’ But this year [2020], a survey found that 60 percent of residents wanted the rally postponed. At council meetings, people lined up to argue. A nurse warned there wouldn’t be enough hospital beds if the event went forward, while a business owner said she would lose her building if it didn’t. Calling off this year’s rally, its 80th anniversary, would mean a loss of around USD 2 million for the city, authorities said. It had only been done during World War II. ‘A risk that they accepted’ In the run-up to the rally, officials estimated that 250 000 people would come. The actual number, according to the South Dakota Transportation Department, was over 460 000 — down just 7 percent from 2019. They came in the greatest numbers from South Dakota, source of an estimated 93 000 attendees, or 1/5 of the total, according to calculations by the Center for New Data. Minnesota ranked 2nd, with an estimated 31 000 people, followed by Colorado with 29 000. Many traveled hundreds of miles: 21 000 rallygoers are believed to have come from Texas, and 20 800 from California. Virus’s uncertain path Because symptoms of the coronavirus can take days to surface, rally attendees were unlikely to know they had been infected until returning home. Without a nationally coordinated contact-tracing strategy, the job of identifying chains of transmission was left to a patchwork of local and state health departments with varying approaches, leadership, and staffing. Typically, such efforts focus on determining a person’s contacts after they became infectious — and stopping those people from spreading the virus — rather than on pinpointing the source of an infection. Genomic sequencing, which other countries have harnessed to determine the path of an outbreak, has been underused in the United States. And because it requires culturing and sequencing active virus, the rally is too far in the past for it to be of service now, said Michaud, the Kaiser Family Foundation epidemiologist. So even as the Dakotas and the Upper Midwest began seeing infections climb, it is impossible to say precisely how many of those cases originated at the rally — or how many of those might have ignited additional clusters elsewhere. But other countries offer examples of more robust and coordinated contact-tracing efforts, Michaud said. Japan uses what’s called retrospective contact tracing — working backward to determine where a person was infected and who else may have gotten the virus there, he said. It’s particularly effective in dealing with the coronavirus, which is often transmitted by a small number of people infecting many others in clusters. It was “fairly obvious” that a gathering the size of the motorcycle rally represented a risk, Michaud said — and more rigorous contact tracing could have revealed the actual impact. It might also have prevented some of the secondary and tertiary spread. Hospitals have seen the effects. David Basel, vice president of clinical quality at Avera Medical Group, which has locations on the east side of the state, said on [30 Sep 2020] that facilities had been “busy, and we’re feeling it.” COVID-19 cases make up 10 percent of patients, he said. “The thing that quite honestly scares us most is personnel,” he said. State health officials, who linked 125 cases to Sturgis, have not tied the surge to the rally, however. They note it overlapped with school openings and end-of-summer restlessness. “Anytime you’re bringing individuals together, you’re going to have times where you’re having Noem, the governor, attributed the rise in cases to increases in testing, echoing President Trump’s explanation of growing US infections. “That’s normal, that’s natural, that’s expected,” she told the Associated Press. She did not explain how extra testing could have accounted for the rise in hospitalizations in the state, which hit record highs in October [2020]. And the increases in coronavirus infections spread beyond South Dakota, post-rally. In Crook County, Wyoming, CH started feeling sick a week afterward but isn’t sure whether she was infected there — or whether health officials counted her case as Sturgis-related. CH, who said motorcycle riding is “kind of in my blood,” was mostly avoiding crowds but kept her annual tradition of going to Sturgis and attended a concert there, viewing it as safe because she sat outdoors. She started feeling sick a week afterward and went to the hospital after waking up one morning feeling like “death had crawled in the bed with me.” [Byline: Brittany Shammas, Lena H. Sun; Jacqueline Dupree contributed to this report] — [In the absence of a consistent national approach to dealing with the
Communicated by:
ProMED-mail (from
“Overdispersion and super-spreading of this virus are found in research across the globe. A growing number of studies estimate that a majority of infected people may not infect a single other person. A recent paper found that in Hong Kong, which had extensive testing and contact tracing, about 19 percent of cases were responsible for 80 percent of transmission, while 69 percent of cases did not infect another person. This finding is not rare: multiple studies from the beginning have suggested that as few as 10-20 percent of infected people may be responsible for as much as 80-90 percent of transmission and that many people barely transmit it.”
[3] USA (Sturgis, South Dakota): motorcycle rally
Date: Sat 17 Oct 2020
Source: The Washington Post [abridged, edited]
500 000-person gathering played a role in the outbreak now consuming the Upper Midwest.
But experts say that tally represents just the tip of the iceberg, since contact tracing often doesn’t capture the source of an infection, and asymptomatic spread goes unnoticed.
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As the coronavirus scuttled gatherings big and small, from the 2020 Olympics to birthday parties, weddings, and funerals, Sturgis officials mulled postponing this year’s rally. The event is synonymous with the 7000-person city nestled amid state and national park land, where the Harley-Davidson Rally Point Plaza is a defining feature downtown.
The rally unfolded in August [2020] as it always had.
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What happened afterward was, in certain respects, very clear. South Dakota, which had the most attendees, saw coronavirus cases surge within weeks of the rally’s [16 Aug 2020], with the 7-day rolling average going from 84 on [6 Aug 2020] to 214 on [27 Aug 2020]. The numbers remained elevated into October [2020]: the 1st day of the month [October 2020], the 7-day rolling average was 434. The state is 2nd in the nation in cases per capita behind North Dakota, with numbers high enough for the Harvard Global Health Institute to recommend stay-at-home orders. But precisely how that outbreak unfolded remains shrouded in uncertainty.
“If we started to lose personnel to them coming down with COVID, that would be probably the biggest risk to us.” 3 of the 4 South Dakota counties estimated to have the highest share of Sturgis attendees also saw cases spike post-rally. The increase was most pronounced in Pennington County, which is just outside Sturgis. Its 7-day rolling average of new cases leaped from 8 on [6 Aug 2020] to 34 on [27 Aug 2020].
COVID-19 transmission,” state epidemiologist Joshua Clayton said last month [September 2020]. “That’s a risk whether you’re in South Dakota, or in other states.”
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ProMED-mail
SARS-CoV-2 pandemic, with varying approaches to contact tracing and case investigation, combined with a population that includes individuals not following the NPIs (non pharmaceutical interventions
— use of face masks, social distancing, and frequent hand washing) the true size of the “cluster” associated with the rally may remain estimates that will be modelled, enhanced, and disputed for years to come. It may also serve as a good example to study the approach of developing community herd immunity in the absence of other interventions. – Mod.MPP]