Hanneke Schuitmaker: Well, with working from home and social distancing, it's sort of a blurry timeline for me. I try to get up early in the mornings. The alarm is set for 6:30 a.m., I start work at 7:45 and finish in the evening at 9 or 10 p.m. I do stop occasionally to eat dinner with my family and walk my dog. I cannot say that the hours I spend working on this vaccine are normal. They add up to be a lot because there's so many things happening in parallel. While Im working from home, I do a lot of virtual meetings with my team, with sub teams, and with management to coordinate, to discuss our lab results, and to make decisions.
With much of the world living in lockdown, the spread of the new coronavirus, SARS-CoV-2, that was first detected in China late last year is beginning to slow in some places. As of April 19, 2.4 million had been infected and 165,000 killed by COVID-19, the disease caused by the virus.
While a safe, effective vaccine is still more than a year away, researchers are rushing to repurpose existing drugs and non-drug therapies as well as testing promising experimental drugs that were already in clinical trials.
Even moderately effective therapies or combinations could dramatically reduce the crushing demand on hospitals and intensive care units, changing the nature of the risk the new pathogen represents to populations and healthcare systems. New drugs, together with new diagnostics, antibody tests, patient- and contact-tracing technologies, disease surveillance and other early-warning tools, mean the anticipated next 'wave' of the global pandemic does not have to be nearly as bad as the first.
More than 70 vaccine candidates are also in development around the world, with at least five in preliminary testing in people. Here are some of the drugs, vaccines and other therapies in development:
1. GILEAD SCIENCES: Remdesivir
Type: Drug. Status: Repurposed experimental. Early results: 0-3 Months.
Antiviral drug, originally developed to combat RNA viruses including respiratory syncytial virus. At least 13 trials underway in China, Europe and the United States with preliminary results from two Chinese trials expected as soon as April 2020. A February assessment by the WHO flagged this candidate as the most promising for battling COVID-19.
Initial data are expected to come from studies of patients with relatively severe COVID-19. Because antivirals work best when patients are healthier, those results may show limited effectiveness.
2. Hydroxychloroquine / chloroquine
Type: Drug. Status: Repurposed. Early results: 0-3 Months.
Malaria drug also believed to have antiviral activity. Blocked SARS-CoV-2 entry into cells in an in-vitro experiment. In one small French study, some COVID-19 patients showed improvements but there was no way to know if the drug was the reason. Results published in April from another study in France and one in China found no benefit in patients treated with the drug. Dozens more clinical studies are underway around the world.
3. ROCHE: Actemra (tocilizumab)
Type: Drug. Status: Repurposed. Early results: 0-3 Months.
Monoclonal antibody approved for rheumatoid arthritis and also for treating the "cytokine storm" immune overresponse in cancer patients. Fifteen registered trials in China, Europe and the United States are testing it on COVID-19 patients, alone or in comparison to other therapies. One French trial is looking at 28-day effects on COVID-19 in patients with advanced or metastatic cancer.
4. SANOFI, REGENERON PHARMACEUTICALS: Kevzara (sarilumab)
Type: Drug. Status: Repurposed. Early results: 0-3 Months.
Monoclonal antibody approved for inflammatory arthritis, and in trials targeting the "cytokine storm" immune response in severely ill COVID-19 patients. Regeneron's chief scientific officer has said initial data on effectiveness could come by late April.
5. NOVARTIS, INCYTE: Jakavi (ruxolitinib)
Type: Drug. Status: Repurposed. Early results: 0-3 Months.
Developed to treat inflammatory and autoimmune diseases, and in late-stage development as a cream for atopic dermatitis. One trial each in Canada and Mexico will test the drug in COVID-19 patients with severe respiratory symptoms associated with the "cytokine storm" immune response, with preliminary results expected by June 2020. In the United States, Novartis established a managed access program for use in severe/very severe COVID-19 illness on April 7.
6. MODERNA/NIAID: mRNA 1273
Type: Vaccine. Status: Experimental. Early results: 0-3 Months.
RNA vaccine made with messenger-RNA (mRNA) encoding the spike protein of SARS-CoV-2 encapsulated in a lipid nanoparticle. The phase 1 trial with 45 subjects aged 18-55 at three locations in the United States will evaluate the vaccine's safety and provide early data on the immune response it induces. Trial completion is anticipated to be June 1, 2020.
Type: Non-drug therapy. Early results: 0-3 Months.
Blood plasma from recovered COVID-19 patients is transfused into patients who are currently ill, in the hope the freshly-made antibodies it contains will help fight the virus. The method has been used for more than 100 years and carries little risk of harm or side effects. Small case studies suggest it may help reduce virus levels, and controlled trials are in progress in China, Europe and the United States to gather stronger evidence for a benefit. Results published in April from a study in 10 patients with severe illness in China found significant improvement compared to similar patients who did not receive the treatment.
Immediately available and already in limited use, but supply of plasma from recovered patients may not be sufficient to meet all needs. Further studies of recovered patients must also determine if everyone produces a full immune response to the infection, including "neutralizing antibodies," at sufficiently high levels to become donors.
8. ABBVIE: Kaletra (lopinavir/ritonavir)
Type: Drug. Status: Repurposed. Early results: 0-3 Months.
Antiviral combination used to treat and prevent HIV infections. More than twenty trials around the world are testing the drug as a COVID-19 treatment or post-exposure prophylaxis for people with high-risk close contact with a confirmed case. Initial results expected as soon as May 2020.
One randomized controlled trial in China published results in March showing no differences in viral load or 28-day mortality among 199 patients. Median time to clinical improvement was one day shorter in patients taking the drug. However the same investigators, doctors at Jinyintan Hospital in Wuhan, said in April that they believe Kaletra, as well as a second drug, bismuth potassium citrate, helped some of the COVID-19 patients they treated.
9. CHONGQING PUBLIC HEALTH MEDICAL CENTER, CHONGQING SIDEMU BIOTECHNOLOGY TECHNOLOGY CO.,LTD: NKG2D-ACE2 CAR-NK cells
Type: Non-drug therapy. Status: Experimental. Early results: 0-3 Months.
NKG2D receptor for the immune system's natural killer (NK) cells paired with the ACE-2 receptor that the coronavirus uses to enter human cells. A multicenter Phase 1/2 trial in 90 patients is testing whether this cell therapy can prevent the SARS-CoV-2 virus from entering cells and multiplying, and will look at efficacy over 28 days in patients with severe or critical COVID-19 pneumonia.
Type: Vaccine. Status: Experimental. Early results: 0-3 Months.
Novavax said its Matrix-M adjuvant would be used with the vaccine candidate - NVX-CoV2373 - to enhance immune responses. Trials in 130 adults is expected to begin in mid-May with preliminary immunogenicity and safety results in July, according to the company.
Strong immunogenicity in animal tests, but might require two doses in humans, which would limit supply.
11. APEIRON BIOLOGICS: RhACE2 APN01
Type: Drug. Status: Experimental. Early results: 3-6 Months.
A recombinant human angiotensin converting enzyme 2 (rhACE2) under Phase-2 clinical development in ALI (Acute Lung Injury) and PAH (Pulmonal arterial hypertension). This synthetic version of the human protein that the novel coronavirus uses to enter cells is being tested in Austria to see if it can block viral entry and decrease viral replication in COVID-19 patients, reducing deaths or need for mechanical ventilation. Preliminary results from the trial that was announced on April 2 are expected in September 2020.
12. SHENZHEN GENO-IMMUNE MEDICAL INSTITUTE: Lentiviral Minigene Vaccines (LV-SMENP)
Type: Vaccine. Status: Experimental. Early results: 3-6 Months.
Engineered minigenes encoding viral antigens; lentiviral vector designed to infect dendritic and T cells to induce immunity. The trial in 100 adults in Shenzen, China, is expected to be complete by July 31, 2020.
13. MURDOCH CHILDREN'S RESEARCH INSTITUTE; UMC UTRECHT: BCG tuberculosis vaccine
Type: Vaccine. Status: Repurposed. Early results: 3-6 Months.
Bacillus Calmette-Gurin tuberculosis vaccine that induces a broad innate immune-system response, which has been shown to protect against infection or severe illness with other respiratory pathogens. Large trials in Australia and the Netherlands are testing whether using BCG to rev-up immune defenses in health workers and the elderly reduces unplanned absenteeism, respiratory illnesses including COVID-19, severe illnesses and deaths. Two additional trials by the Max Planck Institute in Germany of a TB vaccine candidate, VPM1002, are in the works.
14. INOVIO PHARMACEUTICALS, COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS (CEPI): INO-4800
Type: Vaccine. Status: Experimental. Early results: 3-6 Months.
DNA plasmid vaccine delivered into the skin via a patch-style electroporation device. A clinical trial launched on April 3 could yield preliminary data by late summer, according to the company, which has said it can manufacture 1 million doses by year-end for additional trials and emergency use.
15. UNIVERSITY OF AARHUS, DENMARK: Camostat mesylate
Type: Drug. Status: Repurposed. Early results: 6-12 Months.
Protease inhibitor licensed in Japan and South Korea to treat chronic pancreatitis. In vitro experiments found it blocks a mechanism SARS-Cov-2 uses to enter human cells. As of early April, an estimated 180 COVID-19 patients aged 18-110 were being recruited at nine locations in Denmark for a phase 2a trial that will examine 30-day changes in disease severity and mortality, with results expected by December 2020. The University of Tokyo also announced plans for a trial of camostat mesylate and a related drug, nafamostat mesylate, starting as early as April 2020.
Type: Drug. Status: Experimental. Early results: 6-12 Months.
Monoclonal antibody targeting complement activation product C5a. Designed to block a mechanism of inflammation, the drug is also in clinical trials for Hidradenitis Suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum. In early April, a trial in the Netherlands launched to test IFX-1 in patients with severe COVID-19 pneumonia, with preliminary results expected in late October 2020.
17. CANSINO BIOLOGICAL INC./BEIJING INSTITUTE OF BIOTECHNOLOGY: AD5-nCov
Type: Vaccine. Status: Experimental. Early results: 6-12 Months.
Non-replicating viral vector. A single-center phase 1 trial with 108 subjects aged 18-60 in Wuhan, Hubei, China, started in March to test the safety and immune responses generated by a recombinant vaccine that uses another respiratory virus, adenovirus, as a vector. On April 12, a randomized controlled phase 2 trial with 500 participants launched to test varying doses against placebo. Phase 1 completion is in late December 2020, and phase 2 results are expected in January 2021.
18. IMPERIAL COLLEGE LONDON: Aspirin, Clopidogrel, Rivaroxaban, Atorvastatin, Omeprazole
Type: Drug. Early results: 9-12 Months.
Trial of cardioprotective drugs to prevent direct damage to the heart muscle that appears to drive the severity of COVID-19 in certain patients as well as their likelihood of needing invasive critical care. The trial will include more than 3,000 patients in the United Kingdom, with a completion date of March 30, 2021.
19. UNIVERSITY OF OXFORD: ChAdOx1
Type: Vaccine. Status: Experimental. Early results: 12-18 Months.
Non-replicating chimpanzee adenovirus vector. Phase 1/2 trial with 510 subjects aged 18-55 at four centers in the United Kingdom. The trial will test safety and immunogenicity of one or two doses of the vaccine, and is expected to be completed in May 2021.
20. Serology / Antibody Testing
Type: Testing. Status: Experimental. Early results: 0-12 Months.
Governments and academic groups have started to test blood for antibodies indicating that a person has been exposed to the new virus, with or without showing symptoms. The presence of antibodies indicates past infection, but separate, ongoing research is needed to know what type and concentration of virus-neutralizing antibodies protect against a new infection, whether all infections produce a full antibody response, and how long protection might last.
Wide serology testing for antibodies will soon provide a broader understanding of the scope and dynamics of the pandemic, help identify which recovered patients may have some immunity to reinfection and for how long, and also help identify the neutralizing antibodies that could become templates for monoclonal antibody therapies as well as models for desired responses from a vaccine candidate. Data from serology testing are expected to begin appearing within weeks.
Early data on COVID-19 patients in China suggests that most develop varying amounts of antibodies in response to infection. One pre-publication report analyzed plasma from 175 patients and found that a sign of inflammation correlated with higher antibody titers and that younger patients were less likely to produce large amounts of antibodies.
Experts think instances of "reinfection" in recovered patients are more likely relapses in patients whose bodies had not cleared the virus. Data is still lacking on whether mild or symptomless infections generate meaningful antibody responses or protection.
Good, a COVID-19 Vaccine is in Development Will it Be Accessible to All Americans? Health Affairs
Kamran Jebreili/Associated Press
Tennis star Novak Djokovic spoke out against vaccination Sunday and said he would not want to be "forced" to take a vaccine to travel amid the COVID-19 pandemic.
"Personally, I am opposed to vaccination, and I wouldn't want to be forced by someone to take a vaccine in order to be able to travel," Djokovic said in a live Facebook chat. "But if it becomes compulsory, what will happen? I will have to make a decision. I have my own thoughts about the matter, and whether those thoughts will change at some point, I don't know.
"Hypothetically, if the season was to resume in July, August or September, though unlikely, I understand that a vaccine will become a requirement straight after we are out of strict quarantine, and there is no vaccine yet."
A vaccine for COVID-19 is believed to be at least a year away from being made widely available. Several are currently in the testing stage.
Djokovic did not delve into his reasoning for being against vaccination. There is nomedical reasonwhy vaccines would be considered unsafe.
Wimbledon already announced its cancellation, and the French Open has been pushed back to a September start due to the pandemic. It's unclear when either the ATP or WTA would resume. Many tournaments require international travel, which has been heavily restricted as more than2.3 million peoplehave been diagnosed with the virus.
All scheduled tournaments have beenpostponedor canceled until at least July 13.
A potential Covid-19 vaccine will be tested on people for the first time this week, it has been revealed.
The Health Secretary, Matt Hancock, made the revelation as he announced further funding for trials of two leading vaccine projects in the UK.
He said two projects based at Oxford University and Imperial College London were working on a possible vaccination jab to protect people from the virus.
And speaking at today's daily Downing Street briefing, Mr Hancock said both were making "rapid progress."
To help with this, he said Imperial College will receive 22.5 million to support its phase two clinical trials and Oxford will be granted 20 million to fund its clinical trials.
The Oxford project had in conjunction with the regulator "accelerated" the trials process and, as a result, the possible vaccine would be trailed in people from this Thursday, he said.
The government was also investing in manufacturing capability so that if either of these vaccines safely work they can make it available to the British people "as soon as humanely possible", he added.
Mr Hancock said the process for finding a vaccine would take trial and error but he has told UK scientists leading the search he would back them to the hilt and give them every resource they need in order to succeed.
"In the long run the best way to defeat coronavirus is through a vaccine," Mr Hancock said.
"This is a new disease. This is uncertain science but I am certain we will throw everything we've got at developing a vaccine.
"The UK is at the forefront of the global effort.
"We have put more money than any other country in the global search for a vacccine.
"And for all the efforts around the world, two of the leading vaccine developments are taking place here at home at Oxford and Imperial.
"Both of these promising projects are making rapid progress. And I've told the scientists leading them we will do everything in our power to support them.
"In normal times reaching this stage would take years and I am very proud of the work taken so far."
He later added: "The upside of being the first country in the world to develop a successful vaccine is so huge that I am throwing everything at it."
On Sunday, Sarah Gilbert, Professor of Vaccinology at Oxford University said of their project: "The prospects are very good, but it is clearly not completely certain."
She added they had already been given permission to recruit volunteers, take blood tests, explain the process and check their health status.
She said there were many crucial stages to the vaccine development.
These start with immunising healthy 18 to 55-year-olds, before moving into older age groups, looking at the safety and immune response to the vaccine.
"That's important because it's the older population that we really need to protect with the vaccine," she said.
Youve all heard the rosiest scenarios by now.
Vaccines are racing through clinical development at unheard-of speed, helped along by regulators working round the clock to beat Covid-19. And manufacturers have been laying the groundwork for mass production ahead of Phase I results.
The first wave of jabs and meds could break in a matter of months. With the NIH endorsing such remarks as Well have a vaccine by September, everyone from lawmakers to investors and the general public have been willing to buy into the notion that salvation lies right around the corner.
Then along comes a prominent analyst to pour a bucket of cold water on your hope of turning the tide by Christmas.
SVB Leerinks Geoffrey Porges took stock of the promise of global pandemic relief and offered to burst that little bubble for free.
For Porges, the only thing that lies around the corner is another corner. And then more corners. The path to a vaccine is long and hard, he notes. And the reality of that should be factored in as we size up the future.
In our experience it is very unlikely that we will have a general use vaccine in the 6-18 month accelerated timeframe that is being discussed. We believe that a 2-3 year timeline is the most optimistic for seeing a general use vaccine introduced, and as importantly, in the remote possibility that an approved, effective, safe general use vaccine was available a year from now, it would still take several years to confer sufficient herd immunity to prevent endemic spread of COVID19. We believe that achieving herd immunity sufficient to prevent epidemic spread is likely to occur in 2023 or 2024, given a highly accelerated timeline for vaccine development including demonstration of safety and efficacy in humans, and then design, development and implementation of a mass immunization program sufficient to get to a 70-80% immune threshold.
And that, he adds, is his optimistic projection. It could be much, much worse.
Sure, there are more than 70 vaccine programs going on now. But for Porges, if you add it all up, its like handing someone a dart and giving them 1 chance to hit a bulls eye at 24 feet 3 times the regulation distance. Hes also not enthusiastic that the closest vaccines to reality like the mRNA vaccines can pass muster quickly, as they are completely unproven.
Add to that a new virus we dont completely understand and you get a better idea of where Porges is coming from.
We do have the luxury of many different shots on goal with 70+ programs underway (to mix our sporting metaphors), but each one of these only has the same low probability and most of them cant deliver on the optimistic timelines now dominating policy makers and investors outlooks.
The only real shot at getting a vaccine into fast use is by requiring people to take a shot of something that no one knows the full story on with safety and efficacy iffy at best, notes the analyst. And that includes immunizing low-risk people for the sake of the older generation.
So give it 2-3 years for an effective vaccine, then 1-3 years for herd immunity. John Carroll
Almost a month after indicating its looking into testing its star C5 inhibitor Soliris for hospitalized patients with Covid-19, Alexion is going straight into Phase III with its follow-up drug, Ultomiris. The study will involve around 270 patients suffering from severe pneumonia, acute lung injury or acute respiratory distress syndrome and investigate whether Ultomiris can help them survive past 29 days.
The decision was based on early anecdotal information available from compassionate use cases in multiple countries as well as preclinical data suggesting that inhibition of terminal complement can lower cytokine and chemokine levels, thereby reducing lung inflammation.
In the Phase III trial which will include a control arm receiving best supportive treatment investigators will also assess the need for mechanical ventilation, oxygenation, duration of ICU stay and hospitalization, in addition to safety as secondary endpoints. Meanwhile Alexion is still running an expanded access program in the US and France for Soliris. Amber Tong
Apart from developing an efficacious and safe vaccine, a companys ability to manufacture the vaccine swiftly is paramount. Experts, including NIAID director Anthony Fauci, have stressed that the best strategy is for makers to shore up manufacturing even before they have concrete evidence of efficacy so that vaccines can be deployed quickly and widely if proven to be safe and potent.
Now, chiefs of pharmaceutical companies are asking governments to work together and provide substantial funding to assist with shoring up production. Industry alone cant provide all the investment needed now for billions of doses, Sanofi EVP David Loew said in an interview with the Financial Times.
Apart from vaccines, there is a global desperation for raw materials for existing treatments being repurposed and testing. Of particular concern are developing poorer nations, whose access to medical supplies is limited by scanter resources. Executives also worry that the Covid-19 situation will echo what happened in the aftermath of previous outbreaks, such as Ebola and the 2009 flu pandemic as the dust began to settle, companies struggled to maintain funding to develop potential drugs and vaccines for future outbreaks after governments cut them off.
The investment required is too large for any company, said Takeda chief Christophe Weber to the FT. Society will have to finance this huge investment. My fear is the same as after the flu pandemic, when everybody loses interest. Natalie Grover
On Sunday, White House advisor Peter Navarro took to Fox News to accuse China of taking a suite of actions to worsen the ongoing coronavirus crisis.
First of all, the virus was spawned in China. Second of all, they hid the virus behind the shield of the World Health Organization. The third thing they did was basically hoard personal protective equipment and now theyre profiteering from it, Navarro said on Fox News program Sunday Morning Futures.
The outspoken critic of China, who has been tasked by President Trump to work on supply issues relating to the pandemic, on Monday suggested on Fox News that the country is withholding data about early coronavirus infections in order to be the first to develop a vaccine.
One of the reasons that they may not have let us in and given us the data on this virus early, is theyre racing to get a vaccine and they think this is just a competitive business race, its a business proposition so that they can sell the vaccines to the world, he said.
The race to develop a vaccine has heated up, with Chinas CanSino as one of a handful of developers with a vaccine in human testing. Natalie Grover
A new study from Brazil, which suggested the combination of hydroxychloroquine and azithromycin had a significantly positive impact on early-stage suspected Covid-19 cases, was posted as a preliminary manuscript draft on Dropbox last week.
On Monday, the trial was suspended by the National Commission for Ethics in Research (Conep) after the agency discovered that testing was initiated before the company, a So Paulo-based hospital chain, received the greenlight to carry out the research. The researchers in charge were summoned for a hearing this Monday afternoon with the agency to provide clarification on suspected irregularities, according to a report.
There were a number of inconsistencies identified. For one, researchers had told Conep that patients with a confirmed diagnosis of Covid-19 would be included in the trial, but the manuscript released suggested that participants displaying flu-like symptoms without confirmed Covid-19 infections were included in the trial. Initially, the researchers also indicated the trial would enroll 200 participants, but the manuscript the number was closer to 700, the report said. Natalie Grover
For a look at all Endpoints News coronavirus stories, check out our special news channel.
A hospital patient in Stamford, Conn., who has COVID-19 symptoms gets his temperature checked. Severe infections with the novel coronavirus have been unusually high among African Americans and Latinos in many hospitals. John Moore/Getty Images hide caption
A hospital patient in Stamford, Conn., who has COVID-19 symptoms gets his temperature checked. Severe infections with the novel coronavirus have been unusually high among African Americans and Latinos in many hospitals.
Our patient in the emergency bay was not doing well. Beads of sweat lined his forehead and his eyes were closed; all of his energy was focused on breathing. Despite all of his efforts, he was sleepy and confused, telltale signs that his brain was not getting enough oxygen. He would inevitably need intubation heavy sedation and a breathing tube to prevent things from quickly getting worse.
I had to ask his son, a man in his early 20s, if it would be within his dad's wishes to intubate him. The young man was shaking with fear, too scared to speak aloud an answer. There were no other family members to help make this tough decision. As a black physician, I (Dr. Khidir) couldn't help but notice that once again it was a patient of color who was critically ill from what was almost certainly COVID-19.
Across the United States, we are seeing alarming statistics about the disproportionate toll of COVID-19 on Latino and black people. In New York City, the New York Times tells us, coronavirus is twice as deadly for these minorities as for their white counterparts. In both Chicago and Louisiana, black patients account for 70% of coronavirus deaths, even though they make up roughly a third of the population.
At Massachusetts General Hospital, where we practice, an estimated 35% to 40% of patients admitted to the hospital with the coronavirus are Latino that's a 400% increase over the percentage of patients admitted before the outbreak who were Latino.
In the emergency room, conversations about a patient's end-of-life wishes are taking place in broken Spanish, seconds before they get intubated. In the intensive care unit, doctors barely have time to update family members, because they're too bogged down by patient-care tasks to call an interpreter. For patients healthy enough to go home, our usual script around social distancing falls short, as many of our black and Latino patients are unable to self-isolate within large multigenerational households. In addition, many of these patients either are essential workers or live with one they cannot simply "stay home".
In a pandemic that has stretched U.S. health care resources thin, it's not surprising to see a worsening of already existent health care disparities. Several states and organizations have started to release Crisis Standards of Care guidelines in recent weeks these are meant to help hospitals ration critical resources like ventilators and intensive care unit beds, if and when the need is dire.
The overall aim of such guidelines, which can vary in their specifics from state to state and hospital to hospital, is to allocate limited resources to the people who are most likely to benefit from them.
To determine which patients get priority in treatment, several of the CSCs published so far, such as guidelines from Colorado and Massachusetts, recommend that the hospital use frameworks that include the patient's age and "SOFA" score (a measure of how critically ill the patient is at arrival, based on objective laboratory values). Importantly, they also include what we doctors call "comorbidities" other, underlying medical conditions that can put patients who are infected with this virus at a higher risk for worse outcomes.
We know that historically disadvantaged populations including black and Latino patients have a higher burden of the comorbidities traditionally used by hospitals to stratify patients by risk. This is largely because of structural and socioeconomic factors. Studies and statistics suggest that, compared to their white counterparts, black patients are 40% more likely to have high blood pressure, twice as likely to have heart failure, three times as likely to die from asthma-related complications, three times more likely to have chronic kidney disease, twice as likely to be diagnosed with colon and prostate cancer, and represent 44% of the HIV positive population. Similarly, Latino patients are twice as likely to both have and die from diabetes, and twice as likely to have chronic liver disease than non-Hispanic whites.
Although the foundational principle of Crisis Standards of Care guidelines are utilitarian and aim to benefit the greatest number of people while treating "individual cases fairly," a system that penalizes on the basis of comorbidities will undoubtedly and unfairly penalize the populations that are already more vulnerable to those conditions.
Furthermore, given the novelty of COVID-19, we still don't have a complete picture of which factors lead to worse outcomes. While some data suggest that patients with severe COVID-19 are more likely to have hypertension or respiratory or cardiovascular illnesses, there are also findings suggesting that men have more severe disease than women. Yet, the Crisis Standards of Care are not factoring sex into their scoring system. This means that we are arbitrarily choosing metrics to guess which patients will do better, and we're doing so at the expense of populations that have historically been marginalized by the health care system.
COVID-19 is already affecting and killing a disproportionate number of black and Latino patients across the United States. Using comorbidities as a proxy for disease severity to allocate resources, without taking into account race and ethnicity, will almost certainly mean that racial and ethnic minorities will be placed in the "back of the line" for critical care resources.
In order to do the greatest good for the greatest number of people ethically and fairly, standards of care must be informed by the existing inequalities in our country.
While we're not suggesting that comorbidities be removed from crisis standards of care altogether, we urge states to reevaluate current guidelines and include only major comorbidities with a known short-term impact on a patient's prognosis.
States should also track and make publicly available demographic data including race and ethnicity for patients hospitalized with COVID-19 in order to ensure that people of color are not being denied resources disproportionately. Lastly, states should ensure that the committees designing crisis standards of care are composed of a racially and ethnically diverse group of individuals in a way that is representative of their population.
It was devastating enough to have to tell my African American patient's young son that his dad's illness was so life-threatening we needed to place a breathing tube down his throat and send him to the intensive care unit. I can only imagine how he would feel if, in some unfortunate circumstance, we would have to tell him that his father would need to be taken off the ventilator to conserve resources.
Dr. Jossie Carreras Tartak and Dr. Hazar Khidir are residents in Emergency Medicine at Massachusetts General Hospital in Boston.
A week after testing positive for Covid-19, Joshua Fiske drove himself to a New Jersey hospital with a fever nearing 104 and a blood oxygen level extraordinarily low for an athletic 47-year-old. An X-ray revealed pneumonia in both lungs.
He was admitted but his condition worsened: He felt cold enough to shiver under five blankets in one moment, then sweated through his hospital gown the next. He worried he wouldnt pull through. He called his wife to say he loved her. He called his two sons and asked them to take care oftheirmother, then tapped out a letter to them on his phone. He wantedthem to grow into good, kind men,he told them. Above all, he urged, Dont let this event define you.
Among the many mysteries of Covid-19 is why relatively healthy young people suddenly become critically ill or die.
advertisement
One answer is what was happening to Fiske. His body had begun to fight the coronavirus with the immune systems equivalent of thermonuclear weapons proteins so powerful they risk annihilating the body they are supposed to protect. This massive over-reaction, known as acytokine storm, is believed to be a major reason that a growing number of exceedingly fit people find themselves fighting for their lives.
Immune cells release cytokines as part of the normal response to infections, but in many Covid-19 patients, this process gets out of hand, leading to inflammation and fluid buildup in the lungs. The storms pose a dilemma for doctors: Prescribe medications that tamp down the immune system at the wrong moment, and the body will be defenseless against the coronavirus or any opportunistic infection thats taken root. Do nothing, and theres a good chance the massive attack will shut down the lungs and other vital organs.
advertisement
Scientists have begun to study how many patients who become critically ill with Covid-19 experience these storms, which were initially seen in some of the earliest patients hospitalized in Wuhan, China. In one study of 53 patients in China, researchers concluded that three particular cytokines were correlated with disease severity and death. (The paper was posted on a preprint server and hasnt been peer-reviewed.)
The crucial question of what portion of critically ill patients are vulnerable to cytokine storms and why awaits more detailed research, said Randy Cron, a rheumatologist at the Childrens Hospital of Alabama and the University of Alabama at Birmingham. We dont know the numbers, but among previously healthy people ages 20 to 60 who require hospitalization, a significant number are suffering from cytokine storms in addition to the virus, Cron told STAT.
There are not yet data for the number of patients with cytokine storms who require ICU or ventilator care, Cron said. But outside the 85-year-old with hypertension or diabetes, if you are that sick, its very likely that thats what you are experiencing, he said.
Fiske was among the last people anybody would have expected to become seriously ill. A Livingston, N.J., urologist, he took up running seven years ago at the age of 40. Since then, he has completed the New York City marathon, and six half marathons from Philadelphia to Brooklyn, and he was running 16 to 20 miles a week.
On March16, after a day in the operating room, Fiskespiked a fever of 101. Hed been zealous about wearing personal protection equipment, and was shedding his scrubs in the garage and showering in the basement for weeks, but he knew the risks. Because he was a doctor, he was able to get tested for the virus at the hospital where he worked,Overlook Medical Center in Summit.
He felt OK at first, and stayed in his basement. He advised patients and talked to his wife and high-school age sonsby FaceTime. His friend and colleague, an infectious disease specialist named Meher Sultana, prescribed him the antibiotic Zithromax and the anti-malaria drug hydroxychloroquine, an unproven drug combination that has been used to help fight the virus.
But despite regular Tylenol, Fiskes fever persisted, and Sultana and his dad, Steven, a gastroenterologist, didnt like how he looked. On March 23, he went to the hospital.
His oxygen level was 91 percent, extraordinarily low for someone who was in such good shape. And although his lungs didnt hurt, an X-ray revealed the double pneumonia. He went quickly to an isolated room with a sliver of a window from which a nurse, Kasey Welch, could monitor him from so she wouldnt have to change her PPE every time she left his room. They, too, began to FaceTime.
Sultana prescribed intravenous fluids, Tylenol, and vitamin C, which did not help. He began to doubt he would survive, but his wife, Isabella, remained optimistic, summoning the memory of her Jewish grandmother, whod survived the Holocaust in Poland by hiding in the woods with her sister and Isabellas father. Some people pray to God, I prayed to my grandmother, she said.
Still, things were not looking good. It hurt to talk, and he labored even to shift positions in bed.
He just wasnt getting better, and he was starting to have a toxic look, Sultana said. I was getting very concerned about the possibility of permanent harm to his lungs.
On March 25, she and Fiskes father discussed the possibility of moving Josh to the intensive care unit and putting him on a ventilator, but that posed a separate array of dangers. The machines, while sometimes life-saving, can trigger a cascade of inflammation that leads to organ damage. Sultana found herself in the same position as doctors from China to Italy, from Spain to Argentina: fighting a virus that had been spreading in people for only for several months, and about which hardly anything was known. There was scant scientific literature to consult, and no playbook to follow.
Some doctors were discussing the possibility that many otherwise robust patients were experiencing cytokine storms. One key sign of that was the bodys levels of ferritin, a protein in the body that binds to iron.
Between admission on March 23 and the following day, Fiskes ferritin skyrocketed from 1,712 to 4,316 micrograms per liter, more than 10 times the normal amount. His level of C-reactive protein, another indicator of inflammation and potential cytokine storm, was 15 times the normal reading.
Sultana was running out of options, and she had to act quickly. She researched the anecdotal reports on treatments with potential against the coronavirus. One was a powerful anti-inflammatory drug often used to treat rheumatoid arthritis, an autoimmune disease in which the immune system also goes into overdrive, attacking the body. She reasoned that Fiske might respond to this drug, called Actemra, which inhibits a particular cytokine called IL-6. Following promising results in China when the drug was used off-label in Covid-19 patients, the FDA had approved its use in U.S. clinical trials in March. (Reports from Italy using a similar drug, Kezvara, showed similar outcomes; it is now in global clinical trials.)
None of this is how medicine is supposed to be practiced in the data-centric 21st century, but Sultana and her colleagues across the world have found themselves flinging any plausible weapon at the virus.
I couldnt even lie to him and say, Youre going to be OK,' Sultana said.
Fiskes father, 72, relied on more cinematic language to describe how he felt about the possibility he might lose his son. I dont panic easily, Steven Fiske said. But I was sad and scared for the first time in my medical career. I had to face the fact that medicine might not save my own son, who was another doctor.
This virus, Steven Fiske said, is a combination of Alien, The Day the Earth Stood Still, The Andromeda Strain, and Apocalypse Now.'
On the morning of March 26, with Fiskes fever still near 104, Welch gave him the infusion of Actemra. Within two hours, his fever dropped to 99 degrees and his oxygen levels returned to near normal.
It appeared the drug had worked. Youre going to be fine, Sultana reassured him by FaceTime.
Fiske stayed in isolation for four more days, improving daily and taking his own vitals so the nurses wouldnt need to use more PPE. On March 30, Welch wheeled Fiske out of his room and into the lobby, where Isabella was waiting. For the first time, she allowed herself to cry.
He spent the next week in his basement, video-consulting with patients. On April 6, after 20 days without touching another person, he climbed the stairs and rejoined his wife and sons, ages 17 and 15.
Fiske has slowly resumed exercising, completing three 10-minute miles and a few sessions on his exercise bicycle. And last week, he returned to the office for the first time in a month. He is happy to be seeing patients in person again.
Soon, he is scheduled to return, as a surgeon, to the hospital where he was so recently treated. His experiences have shifted his perspective.
Ive never been nervous walking into a hospital before, Fiske said. I fought a war, and Im going back to the same battlefield.
Cloe Poisson :: CTMirror.org
A healthcare worker with 1199 SEIU holds a sign demanding more PPE, or Personal Protective Equipment, to protect from Covid-19 during a Caregivers Caravan of union nursing home workers at the state Capitol last week.
State health officials confirmed Monday that more than half of all coronavirus-related deaths in Connecticut involve nursing home residents despite very recent projections that it had been closer to one-third.
The state reclassified the cause of death last week to COVID-19 for some nursing home residents as they worked with local health officials to develop a more uniform method of assessing the pandemics impact on the industry.
We wanted to make sure we were reporting the deaths as accurately as possible, Dr. Lynn Sosa, deputy state epidemiologist, told the CT Mirror on Monday. There was a lot of data coming from multiple sources and we were really doing the best that we can.
Gov. Ned Lamont released a report last Thursday that showed 375 nursing home residents had died from the coronavirus between the pandemics start and April 14.
Thats a 76% percent increase 212 more COVID-19-related deaths among residents from the total reported on April 13.
Coronavirus-related deaths among residents hadnt increased by more than 30 people even once between April 7 and 13.
Put another way, the state report indicated 35% of all coronavirus-related deaths in Connecticut involved nursing home residents through April 13, but by the following day it had swelled to 56%.
Health care experts have warned repeatedly that patients over 60 are among the most vulnerable to complications from the disease and the average age of nursing home admissions in Connecticut is around 80.
Still, the April 14 death total was clearly an outlier or the totals reported earlier in the month likely were too low.
State health officials concluded the data collected from April 7-13 was the problem.
The administration began adding nursing home numbers to its daily briefings on April 7, assigning staff each morning to call all of the states 213 nursing homes, Sosa said. Information from the calls was placed in a spreadsheet that was constantly updated as nursing homes reported developments to the states epidemiology lab.
But even with those daily efforts, there was a hole.
State records on cause of death didnt always match up with those of local health districts.
And health officials discovered it April 14 and 15 when the administration took time off from reporting nursing home data to create a new digital reporting system to replace the daily phone calls.
In some instances, nursing home residents that were showing COVID-19 symptoms but had not been tested before dying were categorized differently. Some were reported as positive. Others simply were reported as having died from respiratory illnesses.
And a shortage of time and available test kits also meant it wasnt always feasible to clarify every uncertain case immediately, Sosa said.
After two days of conferring, state and local health officials had a better, unified understanding on how to identify COVID-19. Officials decided to conclude that the coronavirus was responsible for death when a preponderance of medical evidence pointed in that direction.
The grimmer data sparked calls from state legislators Monday to immediately channel more protective equipment and training into itsnursing home facilities.
We have to act now to stop this from creating any further spread in our most vulnerable population, said Deputy House Minority Leader Vincent J. Candelora, R-North Branford. With the new numbers we have, we have to be sounding the alarm.
Candelora said state government should immediately ensure that all nursing homes have adequate supplies of masks, gloves and other personal protection equipment, as well as the training to use them.
Its important that we have the best data so we can evaluate our response and the direction we go in as a state, said Rep. Toni E. Walker, D-New Haven, co-chairwoman of the Appropriations Committee. I know the administration is trying very hard to do everything that is possible. But the data is saying this is not working.
The Lamont administration announced Sunday it was expanding its emergency Medicaid rate increase for nursing homes from 10% to 15%. But this followed a letter from nursing home industry leaders warning facilities were days away from financial catastrophe due to increased coronavirus-related staffing and equipment costs.
McKnights, an online news site specializing in long-term care issues, published an analysis earlier this month of personal protection equipment cost increases amidst the pandemic.
Mark-ups included: 215% for hand sanitizer; 267% for latex gloves; 1,513% for N95 masks; and 2,000% for disposable gowns.
The Lamont administration also recently announced it would begin visits to every nursing home in the state to better understand their needs.
The states two largest nursing home associations called Monday for more careful government scrutiny of COVID-19 data going forward.
The incidents of COVID-related deaths are increasing in nursing homes, consistent with data indicating the impact the virus has on older populations wrote Matthew Barrett, president of the Connecticut Association of Health Care Facilities and Mag Morelli, president of LeadingAge Connecticut. We need to be sure the data we are collecting and the manner in which it is collected is gathered and reported consistently and accurately so that we can utilize it to the fullest extent in our efforts to fight this historic and unprecedented pandemic.
Staff writer Jacqueline Rabe Thomas contributed to this story.
A man wearing a face mask as a preventive measure against the spread of the new coronavirus walks next to commercial buildings in the Raffles Place financial business district in Singapore on April 14. Roslan Rahman/AFP via Getty Images hide caption
A man wearing a face mask as a preventive measure against the spread of the new coronavirus walks next to commercial buildings in the Raffles Place financial business district in Singapore on April 14.
Robert Muggah is a principal of the SecDev Group and cofounder of the Igarape Institute. His latest book, Terra Incognita, co-authored with Ian Goldin, focuses on the systemic threats facing our world.
Thomas Ermacora is a city futurist, regeneration architect and technology investor, co-author of Recoded City: Co-Creating Urban Futures.
The COVID-19 pandemic brought the world's bustling cities to a screeching halt. The outbreak has revealed how urban centers are the front and last lines of defense against infectious disease outbreaks. They are also the key to leading national and global recovery.
The pandemic hit some cities harder than others. It is exposing the fault lines that stratify our societies, especially inequalities in income, gender, race and opportunity. Decisions made in the coming months not just by national leaders, but governors and mayors, will have generational consequences. Some cities will flourish, emerging more resilient than before. Most will suffer and others will collapse.
The severity of the pandemic is connected fundamentally to governance. Where there is leadership and coordination, as in Copenhagen, Seoul or Taipei, the virus is more rapidly contained. Where there is competition and dysfunction, fatality rates are higher. The coronavirus has exposed the tattered state of the social contract in nations rich and poor. These failures will have consequential knock-on effects.
We are about to start one of the greatest experiments in recent history as cities everywhere emerge from lockdown. The stakes could not be higher. A staggering 81% of the global workforce is affected by full or partial shutdown measures. Most people live pay-check to pay-check and cannot afford to stay isolated.
But this is just the beginning: We can expect waves of infectious disease outbreaks for years until we have a vaccine and strong antiviral options.
Everyone agrees that cities cannot stay in lockdown indefinitely. So how are they expected to cope? In the short-term, face masks, test kits, digital contact tracing, social distancing and other restrictions will be ubiquitous. Measures will vary in intensity and invasiveness from city to city. In China, cellphone-based contact tracing is already the norm with people color-coded according to their risk of infectiousness. Residential management committees are also keeping villagers from moving to cities.
A number of European cities that implemented stringent social distancing measures are now cautiously opening day cares, schools, universities and businesses. States across the U.S. are considering steps to open back up. Cities across Africa, Asia and Latin America are facing hard choices given that, in many areas, social distancing measures were a virtual impossibility to begin with.
After saving lives, an important question facing every mayor is what does a city look like in the COVID-19 era? We identified nine trends that are likely to play out in the months and years ahead.
First, the places where people congregate from sports arenas to shopping malls and will be smartly retrofitted for social distancing. Some are already offering virtual and augmented reality alternatives. We can expect these trends to continue speeding up.
Second, the shift to online retail will be accelerated. Most stores selling products from computers to car parts are moving to cyberspace. Although some of them will recover, the pandemic could be terminal for those that could not survive prolonged supply and demand shocks. Sadly, smaller businesses are most at risk despite being the very assets that contribute to city identity and character.
Third, urban mobility will undergo a series of corrections. For one, public buses, trains and ferries may come back more aggressively than before. Ride-sharing options will slow down until hygienic solutions are available. Self-driving alternatives could start arriving, threatening millions of jobs. More people will want to work from home or take their bikes to work. Cities will give more space to pedestrians, a rare silver lining to the crisis.
Fourth, the way societies consume and produce food in cities will be overhauled. The overdependence on just-in-time global supply chains and meat-based diets is perilous. Cities are fundamentally rethinking local and more sustainable production. Expect to see a boom in vertical and urban gardens, or even better, rooftop and container farming. Likewise, public spaces and parks will be reenvisioned to accommodate food production, as well as to mitigate threats from flooding and storms.
Fifth, privacy and politics will be deeply affected, and mostly for the worse. China is pioneering massive surveillance in the name of population health and marketing its expertise to other nations. COVID-19 not only threatens to disrupt elections and public demonstrations, but intrusive technological responses could rapidly overwhelm other human rights as well.
Sixth, the climate dividend is already revealing itself as fewer people fly, drive and pollute. Residents of some Indian cities can see the Himalayas and people are breathing cleaner air in Beijing. This is an experience that people may not want to relinquish in the new abnormal. But there are also environmental risks from the pandemic, especially as it potentially slows down global efforts to meet lower emissions goals set in the Paris Climate Agreement. City networks such as C40 will become more important than ever.
Seventh, the virus is strengthening social cohesion in some cities. Neighborhood groups are spontaneously coming together online to help the elderly, homeless and migrants. These hyperlocal structures are vital given the repeated failures of federal and state-level responses. If empowered and given more voice, they will play a crucial role in city renewal.
Eighth, COVID-19 is accelerating several social trends that were already underway. It is hastening the shift from structured office environments to more flexible, virtual and home-based work arrangements. Reduced demand for office space will hurt cities, especially their density. It is also drawing attention to the epidemic of loneliness and mental illness in many cities, and could lead to greater efforts to provide appropriate services and solidarity.
All of these COVID-19 trends are reinforcing the central place of digital connectivity, and cyber security, and the functions of residential areas where people live and work. They also underline the ways in which cities need to reimagine their overall vision and design. We can expect to see new urban design standards that combine crisis response with long-term, equitable benefits for society and the environment. The example of Amsterdam stands out, as it moves toward a city planning model built on "doughnut economics."
With over half of the world's population living in cities, they are important for scaling solutions on this pandemic and the next one. Cities have always exhibited the capacity to evolve after crises. There's a reason why people say the city is where the future happens first. If mayors, business leaders and civic entrepreneurs make the right decisions now, many cities might bounce back better than before. The most successful of them will design-in principles of resilience, sustainability and regenerative economics alongside a radical intolerance for inequality.
