You’re Likely to Get the Coronavirus

 In China, Defense, Australia, Air, India, FVEY, Healthcare and Public Health

Most cases are not life-threat­en­ing, which is also what makes the virus a his­toric chal­lenge to con­tain.

In May 1997, a 3‑year-old boy developed what at first seemed like the common cold. When his symp­toms — sore throat, fever, and cough — per­sist­ed for six days, he was taken to the Queen Elizabeth Hospital in Hong Kong. There his cough wors­ened, and he began gasp­ing for air. Despite inten­sive care, the boy died.

Puzzled by his rapid dete­ri­o­ra­tion, doc­tors sent a sample of the boy’s sputum to China’s Department of Health. But the stan­dard test­ing pro­to­col couldn’t fully iden­ti­fy the virus that had caused the dis­ease. The chief virol­o­gist decid­ed to ship some of the sample to col­leagues in other coun­tries.

At the U.S. Centers for Disease Control and Prevention in Atlanta, the boy’s sputum sat for a month, wait­ing for its turn in a slow process of anti­body-match­ing analy­sis. The results even­tu­al­ly confirmed that this was a vari­ant of influen­za, the virus that has killed more people than any in his­to­ry. But this type had never before been seen in humans. It was H5N1, or “avian flu,” dis­cov­ered two decades prior, but known only to infect birds.

By then, it was August. Scientists sent dis­tress sig­nals around the world. The Chinese gov­ern­ment swift­ly killed 1.5 mil­lion chick­ens (over the protests of chick­en farm­ers). Further cases were close­ly mon­i­tored and iso­lat­ed. By the end of the year there were 18 known cases in humans. Six people died.

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This was seen as a successful global response, and the virus was not seen again for years. In part, con­tain­ment was pos­si­ble because the dis­ease was so severe: Those who got it became man­i­fest­ly, extreme­ly ill. H5N1 has a fatal­i­ty rate of around 60 percent—if you get it, you’re likely to die. Yet since 2003, the virus has killed only 455 people. The much “milder” flu virus­es, by con­trast, kill fewer than 0.1 per­cent of people they infect, on aver­age, but are respon­si­ble for hun­dreds of thou­sands of deaths every year.

Severe ill­ness caused by virus­es such as H5N1 also means that infect­ed people can be iden­ti­fied and iso­lat­ed, or that they died quick­ly. They do not walk around feel­ing just a little under the weath­er, seed­ing the virus. The new coro­n­avirus (known tech­ni­cal­ly as SARS-CoV‑2) that has been spread­ing around the world can cause a res­pi­ra­to­ry ill­ness that can be severe. The dis­ease (known as COVID-19) seems to have a fatal­i­ty rate of less than 2 per­cent — expo­nen­tial­ly lower than most out­breaks that make global news. The virus has raised alarm not despite that low fatal­i­ty rate, but because of it.

Coronaviruses are sim­i­lar to influen­za virus­es in that they are both single strands of RNA. Four coro­n­avirus­es com­mon­ly infect humans, caus­ing colds. These are believed to have evolved in humans to max­i­mize their own spread — which means sick­en­ing, but not killing, people. By con­trast, the two prior novel coro­n­avirus out­breaks—SARS (severe acute res­pi­ra­to­ry syn­drome) and MERS (Middle East res­pi­ra­to­ry syn­drome, named for where the first out­break occurred) — were picked up from ani­mals, as was H5N1. These dis­eases were highly fatal to humans. If there were mild or asymp­to­matic cases, they were extreme­ly few. Had there been more of them, the dis­ease would have spread widely. Ultimately, SARS and MERS each killed fewer than 1,000 people.

COVID-19 is already report­ed to have killed more than twice that number. With its potent mix of char­ac­ter­is­tics, this virus is unlike most that cap­ture pop­u­lar atten­tion: It is deadly, but not too deadly. It makes people sick, but not in pre­dictable, unique­ly iden­ti­fi­able ways. Last week, 14 Americans tested pos­i­tive on a cruise ship in Japan despite feeling fine—the new virus may be most dan­ger­ous because, it seems, it may some­times cause no symp­toms at all.

The world has respond­ed with unprece­dent­ed speed and mobi­liza­tion of resources. The new virus was iden­ti­fied extreme­ly quick­ly. Its genome was sequenced by Chinese sci­en­tists and shared around the world within weeks. The global sci­en­tif­ic com­mu­ni­ty has shared genom­ic and clin­i­cal data at unprece­dent­ed rates. Work on a vac­cine is well under way. The Chinese gov­ern­ment enact­ed dra­mat­ic con­tain­ment mea­sures, and the World Health Organization declared an emer­gency of inter­na­tion­al con­cern. All of this hap­pened in a frac­tion of the time it took to even iden­ti­fy H5N1 in 1997. And yet the out­break con­tin­ues to spread.

The Harvard epi­demi­ol­o­gy pro­fes­sor Marc Lipsitch is exact­ing in his dic­tion, even for an epi­demi­ol­o­gist. Twice in our con­ver­sa­tion he start­ed to say some­thing, then paused and said, “Actually, let me start again.” So it’s strik­ing when one of the points he wanted to get exact­ly right was this: “I think the likely out­come is that it will ulti­mate­ly not be con­tain­able.”

Containment is the first step in respond­ing to any out­break. In the case of COVID-19, the pos­si­bil­i­ty (how­ev­er implau­si­ble) of pre­vent­ing a pan­dem­ic seemed to play out in a matter of days. Starting in January, China began cor­don­ing off pro­gres­sive­ly larger areas, radi­at­ing out­ward from Wuhan City and even­tu­al­ly encap­su­lat­ing some 100 mil­lion people. People were barred from leav­ing home, and lec­tured by drones if they were caught out­side. Nonetheless, the virus has now been found in 24 coun­tries.

Despite the appar­ent inef­fec­tive­ness of such mea­sures — rel­a­tive to their inor­di­nate social and eco­nom­ic cost, at least — the crack­down con­tin­ues to esca­late. Under polit­i­cal pres­sure to “stop” the virus, last Thursday the Chinese gov­ern­ment announced that offi­cials in the Hubei province would be going door to door, test­ing people for fevers and look­ing for signs of ill­ness, then send­ing all poten­tial cases to quar­an­tine camps. But even with the ideal con­tain­ment, the virus’s spread may have been inevitable. Testing people who are already extreme­ly sick is an imper­fect strat­e­gy if people can spread the virus with­out even feel­ing bad enough to stay home from work.

Lipsitch pre­dicts that, within the coming year, some 40 to 70 per­cent of people around the world will be infect­ed with the virus that causes COVID-19. But, he clar­i­fies emphat­i­cal­ly, this does not mean that all will have severe ill­ness­es. “It’s likely that many will have mild dis­ease, or may be asymp­to­matic,” he said. As with influen­za, which is often life-threat­en­ing to people with chron­ic health con­di­tions and of older age, most cases pass with­out med­ical care. (Overall, around 14 percent of people with influen­za have no symp­toms.)

Lipsitch is far from alone in his belief that this virus will con­tin­ue to spread widely. The emerg­ing con­sen­sus among epi­demi­ol­o­gists is that the most likely out­come of this out­break is a new sea­son­al dis­ease — a fifth “endemic” coro­n­avirus. With the other four, people are not known to devel­op long-last­ing immu­ni­ty. If this one fol­lows suit, and if the dis­ease con­tin­ues to be as severe as it is now, “cold and flu season” could become “cold and flu and COVID-19 season.”

At this point, it is not even known how many people are infect­ed. As of Sunday, there have been 35 con­firmed cases in the U.S., according to the World Health Organization. But Lipsitch’s “very, very rough” esti­mate when we spoke a week ago (bank­ing on “mul­ti­ple assump­tions piled on top of each other,” he said) was that 100 or 200 people in the U.S. were infect­ed. That’s all it would take to seed the dis­ease widely. The rate of spread would depend on how con­ta­gious the dis­ease is in milder cases. On Friday, Chinese sci­en­tists report­ed in the med­ical jour­nal JAMA an appar­ent case of asymp­to­matic spread of the virus, from a patient with a normal chest CT scan. The researchers con­clud­ed with stolid under­state­ment that if this find­ing is not a bizarre abnor­mal­i­ty, “the pre­ven­tion of COVID-19 infec­tion would prove chal­leng­ing.”

Even if Lipsitch’s esti­mates were off by orders of mag­ni­tude, they wouldn’t likely change the over­all prog­no­sis. “Two hun­dred cases of a flu-like ill­ness during flu season — when you’re not test­ing for it — is very hard to detect,” Lipsitch said. “But it would be really good to know sooner rather than later whether that’s cor­rect, or whether we’ve mis­cal­cu­lat­ed some­thing. The only way to do that is by test­ing.”

Originally, doc­tors in the U.S. were advised not to test people unless they had been to China or had con­tact with some­one who had been diag­nosed with the dis­ease. Within the past two weeks, the CDC said it would start screen­ing people in five U.S. cities, in an effort to give some idea of how many cases are actu­al­ly out there. But tests are still not widely available. As of Friday, the Association of Public Health Laboratories said that only California, Nebraska, and Illinois had the capac­i­ty to test people for the virus.

With so little data, prog­no­sis is dif­fi­cult. But the con­cern that this virus is beyond con­tain­ment — that it will be with us indef­i­nite­ly — is nowhere more appar­ent than in the global race to find a vac­cine, one of the clear­est strate­gies for saving lives in the years to come.

Over the past month, stock prices of a small phar­ma­ceu­ti­cal com­pa­ny named Inovio more than dou­bled. In mid-January, it report­ed­ly discovered a vac­cine for the new coro­n­avirus. This claim has been repeat­ed in many news reports, even though it is tech­ni­cal­ly inac­cu­rate. Like other drugs, vac­cines require a long test­ing process to see if they indeed pro­tect people from dis­ease, and do so safely. What this com­pa­ny—and others—has done is copy a bit of the virus’s RNA that one day could prove to work as a vac­cine. It’s a promis­ing first step, but to call it a dis­cov­ery is like announc­ing a new surgery after sharp­en­ing a scalpel.

Though genet­ic sequenc­ing is now extreme­ly fast, making vac­cines is as much art as sci­ence. It involves find­ing a viral sequence that will reli­ably cause a pro­tec­tive immune-system memory but not trig­ger an acute inflam­ma­to­ry response that would itself cause symp­toms. (While the influen­za vac­cine cannotcause the flu, CDC warns that it can cause “flu-like symp­toms.”) Hitting this sweet spot requires test­ing, first in lab models and ani­mals, and even­tu­al­ly in people. One does not simply ship a bil­lion viral gene frag­ments around the world to be inject­ed into every­one at the moment of dis­cov­ery.

Inovio is far from the only small biotech com­pa­ny ven­tur­ing to create a sequence that strikes that bal­ance. Others include Moderna, CureVac, and Novavax. Academic researchers are also on the case, at Imperial College London and other uni­ver­si­ties, as are fed­er­al sci­en­tists in sev­er­al coun­tries, includ­ing at the U.S. National Institutes of Health. Anthony Fauci, head of the NIH’s National Institute of Allergy and Infectious Diseases, wrote in JAMA in January that the agency was work­ing at his­toric speed to find a vac­cine. During the SARS out­break in 2003, researchers moved from obtain­ing the genom­ic sequence of the virus and into a phase 1 clin­i­cal trial of a vac­cine in 20 months. Fauci wrote that his team has since com­pressed that time­line to just over three months for other virus­es, and for the new coro­n­avirus, “they hope to move even faster.”

New models have sprung up in recent years, too, that promise to speed up vac­cine devel­op­ment. One is the Coalition for Epidemic Preparedness (CEPI), which was launched in Norway in 2017 to finance and coor­di­nate the devel­op­ment of new vac­cines. Its founders include the gov­ern­ments of Norway and India, the Wellcome Trust, and the Bill & Melinda Gates Foundation. The group’s money is now flow­ing to Inovio and other small biotech start-ups, encour­ag­ing them to get into the risky busi­ness of vac­cine devel­op­ment. The group’s CEO, Richard Hatchett, shares Fauci’s basic time­line vision — a COVID-19 vac­cine ready for early phases of safety test­ing in April. If all goes well, by late summer test­ing could begin to see if the vac­cine actu­al­ly pre­vents dis­ease.

Overall, if all pieces fell into place, Hatchett guess­es it would be 12 to 18 months before an ini­tial prod­uct could be deemed safe and effec­tive. That time­line rep­re­sents “a vast accel­er­a­tion com­pared with the his­to­ry of vac­cine devel­op­ment,” he told me. But it’s also unprece­dent­ed­ly ambi­tious. “Even to pro­pose such a time­line at this point must be regard­ed as hugely aspi­ra­tional,” he added.

Even if that idyl­lic year-long pro­jec­tion were real­ized, the novel prod­uct would still require man­u­fac­tur­ing and dis­tri­b­u­tion. “An impor­tant con­sid­er­a­tion is whether the under­ly­ing approach can then be scaled to pro­duce mil­lions or even bil­lions of doses in coming years,” Hatchett said. Especially in an ongo­ing emer­gency, if bor­ders closed and supply chains broke, dis­tri­b­u­tion and pro­duc­tion could prove dif­fi­cult purely as a matter of logis­tics.

Fauci’s ini­tial opti­mism seemed to wane, too. Last week he said that the process of vac­cine devel­op­ment was prov­ing “very dif­fi­cult and very frus­trat­ing.” For all the advances in basic sci­ence, the process cannot pro­ceed to an actual vac­cine with­out exten­sive clin­i­cal test­ing, which requires man­u­fac­tur­ing many vac­cines and metic­u­lous­ly mon­i­tor­ing out­comes in people. The process could ulti­mate­ly cost hun­dreds of mil­lions of dol­lars — money that the NIH, start-ups, and uni­ver­si­ties don’t have. Nor do they have the pro­duc­tion facil­i­ties and tech­nol­o­gy to mass-man­u­fac­ture and dis­trib­ute a vac­cine.

Production of vac­cines has long been con­tin­gent on invest­ment from one of the hand­ful of giant global phar­ma­ceu­ti­cal com­pa­nies. At the Aspen Institute last week, Fauci lamented that none had yet to “step up” and commit to making the vac­cine. “Companies that have the skill to be able to do it are not going to just sit around and have a warm facil­i­ty, ready to go for when you need it,” he said. Even if they did, taking on a new prod­uct like this could mean mas­sive losses, espe­cial­ly if the demand faded or if people, for com­plex rea­sons, chose not to use the prod­uct.

Making vac­cines is so dif­fi­cult, cost inten­sive, and high risk that in the 1980s, when drug com­pa­nies began to incur legal costs over alleged harms caused by vac­cines, many opted to simply quit making them. To incen­tivize the phar­ma­ceu­ti­cal indus­try to keep pro­duc­ing these vital prod­ucts, the U.S. gov­ern­ment offered to indemnify anyone claiming to have been harmed by a vac­cine. The arrange­ment con­tin­ues to this day. Even still, drug com­pa­nies have gen­er­al­ly found it more prof­itable to invest in the daily-use drugs for chron­ic con­di­tions. And coro­n­avirus­es could present a par­tic­u­lar chal­lenge in that at their core they are, like influen­za virus­es, a single strand of RNA. This viral class is likely to mutate, and vac­cines may need to be in con­stant devel­op­ment, as with the flu.

“If we’re putting all our hopes in a vac­cine as being the answer, we’re in trou­ble,” Jason Schwartz, an assis­tant pro­fes­sor at Yale School of Public Health who stud­ies vac­cine policy, told me. The best-case sce­nario, as Schwartz sees it, is the one in which this vac­cine devel­op­ment hap­pens far too late to make a dif­fer­ence for the cur­rent out­break. The real prob­lem is that pre­pared­ness for this out­break should have been hap­pen­ing for the past decade, ever since SARS. “Had we not set the SARS-vac­cine-research pro­gram aside, we would have had a lot more of this foun­da­tion­al work that we could apply to this new, close­ly relat­ed virus, ” he said. But, as with Ebola, gov­ern­ment fund­ing and phar­ma­ceu­ti­cal-indus­try devel­op­ment evap­o­rat­ed once the sense of emer­gency lifted. “Some very early research ended up sit­ting on a shelf because that out­break ended before a vac­cine needed to be aggres­sive­ly devel­oped.”

On Saturday, Politico reported that the White House is prepar­ing to ask Congress for $1 bil­lion in emer­gency fund­ing for a coro­n­avirus response. This request, if it mate­ri­al­ized, would come in the same month in which President Donald Trump released a new budget proposal that would cut key ele­ments of pan­dem­ic pre­pared­ness — fund­ing for the CDC, the NIH, and for­eign aid.  

These long-term gov­ern­ment invest­ments matter because cre­at­ing vac­cines, antivi­ral med­ica­tions, and other vital tools requires decades of seri­ous invest­ment, even when demand is low. Market-based economies often strug­gle to devel­op a prod­uct for which there is no imme­di­ate demand and to dis­trib­ute prod­ucts to the places they’re needed. CEPI has been touted as a promis­ing model to incen­tivize vac­cine devel­op­ment before an emer­gency begins, but the group also has skep­tics. Last year, Doctors Without Borders wrote a scathing open letter, saying the model didn’t ensure equi­table dis­tri­b­u­tion or afford­abil­i­ty. CEPI sub­se­quent­ly updat­ed its poli­cies to fore­front equi­table access, and Manuel Martin, a med­ical inno­va­tion and access advis­er with Doctors Without Borders, told me last week that he’s now cau­tious­ly opti­mistic. “CEPI is absolute­ly promis­ing, and we really hope that it will be suc­cess­ful in pro­duc­ing a novel vac­cine,” he said. But he and his col­leagues are “wait­ing to see how CEPI’s com­mit­ments play out in prac­tice.”

These con­sid­er­a­tions matter not simply as human­i­tar­i­an benev­o­lence, but also as effec­tive policy. Getting vac­cines and other resources to the places where they will be most help­ful is essen­tial to stop dis­ease from spread­ing widely. During the 2009 H1N1 flu out­break, for exam­ple, Mexico was hit hard. In Australia, which was not, the gov­ern­ment prevented exports by its phar­ma­ceu­ti­cal indus­try until it filled the Australian government’s order for vac­cines. The more the world enters lock­down and self-preser­va­tion mode, the more dif­fi­cult it could be to sober­ly assess risk and effec­tive­ly dis­trib­ute tools, from vac­cines and res­pi­ra­tor masks to food and hand soap.

Italy, Iran, and South Korea are now among the coun­tries report­ing quick­ly grow­ing num­bers of detect­ed COVID-19 infec­tions. Many coun­tries have respond­ed with con­tain­ment attempts, despite the dubi­ous effi­ca­cy and inher­ent harms of China’s his­tor­i­cal­ly unprece­dent­ed crack­down. Certain con­tain­ment mea­sures will be appro­pri­ate, but widely ban­ning travel, clos­ing down cities, and hoard­ing resources are not real­is­tic solu­tions for an out­break that lasts years. All of these mea­sures come with risks of their own. Ultimately some pan­dem­ic respons­es will require open­ing bor­ders, not clos­ing them. At some point the expec­ta­tion that any area will escape effects of COVID-19 must be aban­doned: The dis­ease must be seen as everyone’s prob­lem.  

Source: Defense One

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