H5N1

WHO: Solidarity Therapeutics Trial produces conclusive evidence on the effectiveness of repurposed drugs for COVID-19 in record time

A WHO news release: Solidarity Therapeutics Trial produces conclusive evidence on the effectiveness of repurposed drugs for COVID-19 in record time. The full release, with my bolding:

In just six months, the world’s largest randomized control trial on COVID-19 therapeutics has generated conclusive evidence on the effectiveness of repurposed drugs for the treatment of COVID-19. 

Interim results from the Solidarity Therapeutics Trial, coordinated by the World Health Organization, indicate that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalized patients. 

The study, which spans more than 30 countries, looked at the effects of these treatments on overall mortality, initiation of ventilation, and duration of hospital stay in hospitalized patients. Other uses of the drugs, for example in treatment of patients in the community or for prevention, would have to be examined using different trials.  

The progress achieved by the Solidarity Therapeutics Trial shows that large international trials are possible, even during a pandemic, and offer the promise of quickly and reliably answering critical public health questions concerning therapeutics. The results of the trial are under review for publication in a medical journal and have been uploaded as preprint at medRxiv available at this link: https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1 

The global platform of the Solidarity Trial is ready to rapidly evaluate promising new treatment options, with nearly 500 hospitals open as trial sites.  

Newer antiviral drugs, immunomodulators and anti-SARS COV-2 monoclonal antibodies are now being considered for evaluation. 

Curing COVID-19

An editorial in The Lancet Infectious Diseases: Curing COVID-19.

As the COVID-19 pandemic moves into its 10th month, greater patient survival suggests that treatment of severe disease has improved. How much of this improvement is due to better supportive care and how much to pharmaceuticals is a matter of debate. Given the huge effort that the biomedical community has put into finding drugs to treat COVID-19, with thousands of trials completed and ongoing, it's worth taking stock of the evidence for what has worked and what has not. 

The hunt for COVID-19 treatments has become extraordinarily politicised, and no more so than with the aminoquinoline drugs chloroquine and hydroxychloroquine. Early observational studies suggested a beneficial effect of treatment with these cheap drugs, leading to acclamation by US President Trump. However, randomised controlled trials (RCTs) in hospitalised patients have shown no effect of hydroxychloroquine in reducing mortality. One RCT hinted at an effect when used as post-exposure prophylaxis, but this was not statistically significant. 

Unless new, high-quality evidence emerges, the aminoquinolines appear to have no future in the management of COVID-19. Remdesivir, an antiviral, was also the subject of White House fanfare. The US Government has attempted to corner the market for this costly drug but results of clinical trials are ambiguous. One review concluded that remdesivir may reduce time to clinical improvement and decrease mortality but had no effect on need for invasive ventilation or length of hospital stay. A subsequent RCT found no effect on mortality. Although approved to treat COVID-19 in the USA and Europe, conclusive evidence to support remdesivir is lacking. 

For other antivirals, there is no good evidence for efficacy of favipiravir, although it has been approved in Russia, and the lopinavir/ritonavir combination showed no clinical benefit in the UK RECOVERY RCT.  

Immunomodulators to treat COVID-19 are being widely tested in clinical trials. Among the front-runners, evidence to support use of tocilizumab, a monoclonal antibody against interleukin-6 receptors, comes largely from observational studies. Roche, the manufacturer, has announced that the drug did not improve clinical status in a phase 3 RCT among patients with severe COVID-19-associated pneumonia. Similarly, good quality evidence on the use of convalescent plasma is still awaited. 

Large RCTs such as RECOVERY, which includes tocilizumab and convalescent plasma groups, should provide answers. Immunomodulators that do work are the corticosteroids. In the dexamethasone group of RECOVERY, deaths were reduced by 35% in ventilated patients and by 20% among those receiving oxygen only compared with those in the standard care group. 

An RCT of dexamethasone done in Brazil further supports the beneficial effect of the drug. The REMAP-CAP RCT of hydrocortisone—another corticosteroid—versus placebo in patients with severe COVID-19 showed a 93% improvement in the intervention group in days when organ support was not needed. Based on these findings, WHO guidelines recommend corticosteroids in patients with severe and critical COVID-19. 

Is targeted treatment reducing deaths as the disease continues to sweep around the world? Where there has been a resurgence of COVID-19 cases to levels at least as high as when the pandemic first struck in the spring, such as in the USA, France, and Spain, it has not been followed by a comparable increase in deaths, nor of people requiring admission to hospital. Thus, treatment alone cannot be responsible for saving lives.

Possible explanations for the recent disparity in cases and deaths include more widespread testing, meaning that the number of cases being detected is closer to the true burden of infection, whereas the accuracy of counting deaths remains unchanged; lower viral load at the point of transmission, and hence less severe disease, because of non-pharmaceutical measures such as mask wearing; and changes in the distribution of cases towards younger age groups. 

Data from England show that until recently cases have been fairly evenly distributed across all ages from 20 years upwards, but by the last 2 weeks of August cases in people aged 20–39 were about ten times the number in those aged 70 or more. Risk of COVID-19 death in young people is tiny compared with the elderly. However, cases in the young might yet spill over into older people, and the long-term consequences of non-fatal disease are unknown. 

Whatever the reasons for apparent declining mortality, the impact of drug treatments on the COVID-19 pandemic is still limited. The massive research effort needs to bear fruit with a broader range of effective therapies.

Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis

Today's big story is in JAMA: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. Excerpt:

Key Points 

Question  Is administration of systemic corticosteroids associated with reduced 28-day mortality in critically ill patients with coronavirus disease 2019 (COVID-19)? 

Findings  In this prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died, 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66). 

Meaning  Administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality in critically ill patients with COVID-19.  

Abstract 

Importance  Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.  

Objective  To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.  

Design, Setting, and Participants  Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. 

The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. 

Exposures  Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). 

Main Outcomes and Measures  The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. 

Results  A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). 

There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). 

Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.  

Conclusions and Relevance  In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

WHO has issued a clinical guidance on the use of corticosteroids for COVID-19.

What happens when COVID-19 collides with flu season?

Via JAMA: What Happens When COVID-19 Collides With Flu Season? Excerpt:

At a February 26 press conference, President Donald J. Trump said of the novel coronavirus, “This is like a flu,” and expressed surprise that as many as 69 000 people in the US die of influenza every year. 

However, the ensuing 5½ months have shown that coronavirus disease 2019 (COVID-19) is far deadlier and less predictable than seasonal influenza. Unlike influenza, COVID-19 does not appear to be seasonal, given the ever-increasing numbers of US cases this summer. 

So beginning this fall, the US for the first time will have to deal with a flu season wrapped in a global pandemic. Or, as the headline on a recent editorial by Edward Belongia, MD, and Michael Osterholm, PhD, MPH, described it, “a perfect storm.”  

Many questions remain about how flu season might affect the pandemic, and vice versa. For example, would coinfection with influenza worsen the course of COVID-19? Experts also aren’t certain whether influenza vaccination could help protect against COVID-19 or whether steps taken to mitigate COVID-19 will reduce the burden of the coming flu season.  

Some hints have come from preliminary research conducted in China, where influenza was still widely circulating when the first novel coronavirus infections emerged, and in the southern hemisphere, which is currently in the midst of its flu season.  

At least 2 things are clear: Quicker and more widely available testing is needed to distinguish between COVID-19 and influenza, which have similar symptoms, at least at first, but require different treatments. On top of that, a severe influenza season—the result of more virulent strains, inadequate vaccination rates, or a combination of both—coupled with a COVID-19 pandemic that shows no signs of abating, could overwhelm already taxed emergency departments and intensive care units.  

As pulmonary and critical care specialist Benjamin Singer, MD, wrote in a recent editorial, influenza and other causes of pneumonia represent the eighth leading cause of US deaths in nonpandemic years. 

“We can expect that the new reality of COVID-19 will only complicate the next influenza season,” Singer, of the Northwestern University Feinberg School of Medicine, concluded in his editorial.  

Flu-Like but Not Alike 

Distinguishing between influenza and COVID-19 “has important prognostic implications,” Singer said in an interview. “In many ways it matters that you find out quickly.” 

While the course of influenza is rapid, COVID-19 “kind of limps along a little bit,” he said. Knowing the reason for a patient’s respiratory symptoms “helps inform what you can expect.”  

Identifying the cause, of course, helps determine how best to treat respiratory symptoms, Singer noted. Although supportive care for influenza and COVID-19 is similar, drug treatments don’t overlap, he said. 

“We have things that we can do for COVID if we know someone’s infected,” he said. “If they have influenza, we can give antivirals targeted against influenza.” 

But mistakenly treating patients with influenza as though they have COVID-19 is wasteful and potentially harmful, Singer said.

COVID-19: Old-school treatment for a 21st century pandemic

Via The Los Angeles Times: Column One: Old-school treatment for a 21st century pandemic. Excerpt:

A few weeks after the new coronavirus arrived on U.S. shores, Dr. Arturo Casadevall hatched a plan to beat back the outbreak with a medical advance so powerful it had earned a Nobel Prize. 

In 1901.  

That’s when Dr. Emil Adolf von Behring was honored for pioneering the use of so-called convalescent serum as a treatment for diphtheria. In 1892, the Prussian bacteriologist infected horses with the pathogen that causes the deadly disease. If the beasts recovered, Von Behring harvested their blood, removed its red blood cells and clotting proteins, and introduced the resulting antibody-rich fluid into the bloodstreams of human diphtheria patients.  

Until a diphtheria vaccine came into broad use in the 1930s, Von Behring’s daring experiments saved countless lives. At the end of the 19th century, diphtheria, known as “the strangling angel,” was the 10th most common cause of death in the United States, and a pitiless killer of children. 

Convalescent serum would go on to become a mainstay of treatment for measles, mumps, tetanus, smallpox and polio before the “era of vaccine” began in the late 1940s. 

“It’s a beautiful history,” Casadevall, a microbiologist and physician at Johns Hopkins University, said with wistful ardor. “It was the birth of immunology.” 

Amid a pandemic response that promises marvels of genetic engineering, vaccines developed at “warp speed” and artificial intelligence at the bedside, it takes courage for a scientist to dust off a remedy from the history books and propose it as modern medicine. 

The yellowish elixir now drawn from the blood of recovered COVID-19 patients is plasma, which retains some clotting factors. It has been tried against the Ebola virus and novel strains of influenza, only to be shelved when vaccines became available. 

Reviving the 19th century invention to fight a 21st century pandemic is no job for the faint of heart. It will generate neither profits nor scientific glory. Yet to navigate a gauntlet of clinical trials and logistical challenges, it does require a mighty intellect, a heap of energy, the ability to muster an army of skilled recruits and a knack for fundraising. 

And so, nearly every night for five months, Casadevall and two longtime colleagues — Dr. Michael Joyner of the Mayo Clinic and Dr. Liise-anne Pirofski of Albert Einstein College of Medicine — have met online to plot the potential comeback of convalescent plasma. They hope it can become both a treatment for COVID-19 and a way to protect people at high risk of coronavirus infection from becoming ill.  

All in their 60s and well into accomplished careers at leading medical institutions, this trio might have spent the pandemic engaged in quieter pursuits. Instead, the three are putting immune system proteins from recovered patients through modern scientific trials, hoping to buy time for other medical advances to come along. 

They’ve created the National COVID-19 Convalescent Plasma Project, a consortium of 260 doctors and scientists from 57 institutions around the country. Members of their coalition have launched more than 50 laboratory studies and clinical trials, and as of Thursday, 79,059 patients had been treated under the project’s experimental “compassionate use” program. Preliminary findings are expected soon. 

Their passion has them living on “COVID time,” practicing science at all hours of the night and day as kids and spouses hover near their makeshift home offices. The pace of research has been compressed beyond recognition.

Steroid found to help prevent deaths of sickest COVID-19 patients

Via The Guardian: Steroid found to help prevent deaths of sickest coronavirus patients.

A cheap steroid has become the first life-saving treatment in the Covid-19 pandemic, described by scientists as a major breakthrough and raising hopes for the survival of thousands of the most seriously ill.  

Dexamethasone is cheap, available from any pharmacy, and easily obtainable anywhere in the world. Investigators said the drug was responsible for the survival of one in eight of the sickest patients – those who were on ventilators – in the Recovery trial, the biggest randomised, controlled trial of coronavirus treatments in the world.  

“It is the only drug so far shown to reduce mortality and it reduces it significantly,” said Peter Horby, a professor of emerging infectious diseases in the Nuffield department of medicine, at the University of Oxford, and one of the chief investigators of the trial. “It is a major breakthrough, I think.” 

Prof Martin Landray, his co-chief investigator said the sickest patients could begin to be treated with the drug immediately. “The search has been on for a treatment that actually reduces the risk of dying. There hasn’t been one until today.  

“This is a drug that is globally available. This is not an expensive drug. That is immensely important.” 

A total of 2,104 patients were chosen at random to receive 6mg of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days, and were compared with 4,321 patients chosen at random to continue with normal care alone. Among the latter group of patients, 28-day mortality was highest in those who required ventilation (41%), intermediate in those who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).  

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75; p=0.14). 

Based on these results, the use of dexamethasone would prevent one death of around eight ventilated patients, or one of about 25 patients requiring oxygen alone.  

Last week, the Recovery team, who have been trialling seven drugs and will add more, concluded that hydroxychloroquine did not benefit patients in hospital with Covid-19. 

Sir Patrick Vallance, the government’s chief scientific adviser, said: “This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine. 

“This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable. It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.”

Herbal remedy touted by some African governments for COVID-19, despite scientists’ warnings

This does not bode well at all. Via The Globe and Mail, Geoffrey York writes: Herbal remedy touted by some African governments for coronavirus, despite scientists’ warnings. Excerpt and then a comment:

When the government of Madagascar began touting an unproven herbal remedy for the novel coronavirus, one of its most enthusiastic supporters was Tanzanian President John Magufuli, who announced that he would dispatch a plane to pick up a supply of the beverage. 

The two governments are emerging as leaders of a movement to promote what they call “traditional African” solutions to the pandemic, although most African governments are declining to follow their approach. 

So far, five African governments – Tanzania, Equatorial Guinea, Guinea-Bissau, Comoros and the Republic of Congo – have obtained shipments of the Madagascar tonic or promised to import it, even though international experts have warned against it. 

Tanzania is perhaps the least surprising of these. For weeks, Mr. Magufuli has advocated prayers and hot steam as solutions to the virus. He refused to close churches, claiming that the virus “cannot survive in the body of Jesus.”  

His government has conducted only 652 tests for the virus, far fewer than its East African neighbours. After a dramatic rise in coronavirus cases and a wave of mysterious deaths, it has stopped releasing daily reports on case numbers. At last report, five days ago, there were 480 confirmed cases in the country, a 60-per-cent increase over the previous week’s report.  

Mr. Magufuli has blamed “imperialist sabotage” for the high number of positive test results. He suspended two top officials of the national health laboratory on Monday, alleging that the lab’s testing was faulty. But independent experts say the high rate of positive test results – about 74 per cent – is due to the limited amount of testing, which is detecting only those who arrive in hospitals with obvious symptoms. 

Because of the government’s refusal to release daily reports, rumours have flourished. Several deaths among politicians have been blamed on the coronavirus. Videos on social media have shown mysterious “night burials,” with workers wearing masks to protect themselves as they place coffins in the ground under cover of darkness.  

Opposition leaders have condemned the secrecy, alleging that the number of cases is far higher than the government admits. The government has defended its silence, complaining that “false statistics” were leading to panic and unrest in society.  

The Tanzanian government has a track record of secrecy. Last September, the World Health Organization issued a highly unusual statement about Tanzania’s failure to co-operate on suspected Ebola cases. “Despite several requests, WHO did not receive further details of any of these cases from Tanzanian authorities,” the statement said. 

The WHO has also cast doubt on the herbal tonic that Mr. Magufuli aims to import from Madagascar, an Indian Ocean island nation. The global health agency has emphasized that there is currently no cure for the coronavirus, and it has warned against the dangers of self-medication. 

The herbal tea, which Madagascar President Andry Rajoelina is promoting under the brand name “Covid-Organics,” is derived from several local plants, including artemisia, which is used in malaria treatment. Its value against the coronavirus is unproven and largely untested, but Mr. Rajoelina has boasted that it could “change the history of the entire world.”  

The concoction was reportedly tested on fewer than 20 people in a brief trial in Madagascar before the government’s promotional campaign began. Mr. Rajoelina went on national television in Madagascar last month to drink a bottle of the herbal beverage. He said he wanted to popularize the drink “to protect our population.” 

The Madagascar Academy of Medicine has questioned the value of the beverage, calling it scientifically unproven and potentially harmful, especially to children.  

Despite those warnings, soldiers have been going door-to-door in Madagascar’s capital, Antananarivo, to distribute the herbal potion, and Mr. Rajoelina has said it will be “obligatory” for schoolchildren to take the remedy. Hundreds of high-school students have already been forced to drink it, with some reportedly complaining that it tasted bitter and made them nauseous. 

In a statement on Monday, the WHO’s Africa division said it is “critical” that medicinal plants such as artemisia are tested for their efficacy and possible adverse side effects before they are used as a treatment. “Africans deserve to use medicines tested to the same standards as people in the rest of the world,” it said.

Not everyone in Madagascar is buying this nonsense. The Madagascar Tribune has a long editorial that says, among other things:

But we would have liked more vigilance, in what concerns a public health problem. Mass distribution of this product, why not in absolute terms? But in the opacity which surrounds the CVO, with its approximate dosages which cannot, for lack of scientific protocol, apply to all, with its problems of undocumented interactions, with its undocumented side effects, again lack of protocols tests carried out at a minimum, it is possible that the massive distribution of the product has perverse ... massive effects ... It would be regrettable if the distribution of Covid Organics did more visible damage than the pandemic itself.

Picard: There’s no silver bullet for curing COVID-19

Via The Globe and Mail, health columnist André Picard injects common sense into the debate: There’s no silver bullet for curing coronavirus. Excerpt:

The latest drug being touted as the miracle cure for COVID-19 is – pauses to check Twitter – remdesivir.  

News of “positive data” sent Gilead Sciences Inc.’s stock prices soaring and generated a flurry of hyperbolic media stories.  

The U.S. government-sponsored study – which has not yet been peer-reviewed or published – consisted of 1,063 patients in hospital with COVID-19 who were randomly assigned either to receive remdesivir, which is an antiviral drug, or a placebo.  

Those treated with the drug recovered (meaning they were discharged from hospital) after 11 days on average, compared with 15 days for the placebo group. Eight per cent of patients in the remdesivir group died, compared with 11 per cent in the placebo group. 

In other words, yet another drug U.S. President Donald Trump has touted as a “game-changer” is meh.  

Remdesivir appears, at best, to provide a modest reduction, if that, in recovery time for patients who are already recovering. Another rushed, partly completed study, published in The Lancet, found that patients treated with remdesivir had an average recovery time of 21 days, compared with 23 days for patients given a placebo. In other words – no significant difference.  

This doesn’t mean remdesivir is useless. It can, in the lab, stop the replication of the coronavirus. And it appears to do so, at least a bit, in some patients too.  

But it certainly isn’t a silver bullet. Nothing is. 

We have to break out of this ridiculous cycle of publication of partial information followed by overexuberance and then the necessary but always belated reality checks.  

Research takes time and we need to let the scientific process play out. Crossing a potential treatment off the list is not failure, it’s progress.

Both patience and rigorous standards are required despite the understandable yearning for some weapons in the global coronavirus fight.  

Right now, the blunt reality is that there are no effective drug treatments for COVID-19, let alone a cure. Treatment guidelines published earlier this week in the Canadian Medical Association Journal show just how few treatment tools are in the tool box. 

Scientists around the world are trying. There are an estimated 150 drugs under study, and another 70 vaccine candidates. Medicine is throwing everything but the kitchen sink at COVID-19.  

For the most part, scientists and clinicians are repurposing existing drugs. Remdesivir, for example, we developed to treat Ebola. A number of antivirals are being tested, including the HIV drugs lopinavir and ritonavir. 

The antimalarial drugs chloroquine and hydroxychloroquine were much-ballyhooed, described with Trumpian modesty as “the biggest game-changer in the history of medicine” before that balloon burst. 

Hydroxychloroquine is still being studied and used in some cases, but it appears to have limited benefits and potentially severe side effects like heart failure.  

Researchers are also examining drugs that calm the immune system, like interferon beta, which is used to treat multiple sclerosis, and dexamethasone, a steroid used to treat inflammation. 

These drugs have potential because they can squelch an overreaction of the immune system, such as the deadly “cytokine storm” that occurs in some COVID-19 patients. 

Another promising, but not yet ready for prime time, treatment is convalescent plasma – transfusing antibodies from the blood of people who have recovered from COVID-19 into sick patients. This approach, which has been around since the late 19th century, is being tested in Canada, but there are no definitive coronavirus-related results.  

What the world wants – and needs – to fight this pandemic is a vaccine. 

No matter how good treatments are, prevention is preferable. A coronavirus vaccine, if it can be developed, could prevent illness – entirely, or partly.

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Via JAMA Network: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. The key points and abstract: 

Key Points 

Question  What are the characteristics, clinical presentation, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the US?  

Findings  In this case series that included 5700 patients hospitalized with COVID-19 in the New York City area, the most common comorbidities were hypertension, obesity, and diabetes. Among patients who were discharged or died (n = 2634), 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died. 

Meaning  This study provides characteristics and early outcomes of patients hospitalized with COVID-19 in the New York City area. 

Abstract 

Importance  There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). 

Objective  To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. 

Design, Setting, and Participants  Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. 

Exposures  Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. 

Main Outcomes and Measures  Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.  

Results  A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. 

As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). 

Conclusions and Relevance  This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

Wuhan’s ICUs tend to the last few severely ill COVID-19 patients

Via Caixin Global: Wuhan’s ICUs Tend to the Last Few Severely Ill Covid-19 Patients. Excerpt:

On April 7, just one severely ill patient was still hooked up to an extracorporeal membrane oxygenation (ECMO) machine in the ICU of Wuhan’s Leishenshan Hospital.  

His face had a purplish hue and his mouth formed an “O” shape. Tubes of various sizes sprouted from both his head and body — his kidney function was being supported by dialysis and the ECMO machine was putting oxygen into his blood and pumping it around his body. Due to heart problems, his chest heaved violently.  

In the early evening, the monitor in front of the patient’s bed flashed red and sounded an alarm. Doctors and nurses surrounded his bed in an attempt to keep him alive, adjusting his blood’s oxygen level and pressure. After 30 minutes of effort, the siren finally subsided. 

The 68-year-old patient was not only one of the last remaining in Leishenshan, one of two emergency field hospitals built in Wuhan to treat Covid-19 patients, his stay was also one of the longest. The man developed symptoms on Feb. 1, his condition worsened nine days later and he was hospitalized with breathing difficulties, according to Peng Zhiyong, head of the intensive care units at Zhongnan Hospital of Wuhan University and Leishenshan Hospital. 

Both ventilation and intubation were applied to the patient, but his condition showed little improvement. On March 3, he was hooked up to the ECMO machine, and was still plugged in as of April 7. As a result of long-term intubation, he had twice developed infections along witih liver, heart and kidney complications. Yet the doctors wanted to keep trying.  

“The patient is tenacious and wants to live, so we aren’t giving up and want to bring him back,” one doctor said. 

The bed across from the man was occupied by a middle-aged woman, whose face had regained its color. She was able to move about the bed and was preparing to be discharged from the hospital the next day. 

“I think I was in the same shape as him,” she said, gesturing to her neighbor. The woman had developed symptoms in late January, and was in hospital for more than two months. At one point doctors also resorted to treating her with ECMO. She survived. 

“I’m grateful to them from bringing me back from the brink of death,” she said, giving them a thumbs up.  

According to Peng, on April 7, the two ICUs at Leishenshan still had 17 severely ill patients, who had all developed symptoms about two months earlier. In comparison, the average number of days a person takes to clear their body of the virus is 20. Among the 17 patients, about seven had acute illnesses, which doctors had deemed the biggest challenge. 

According to Peng, the severely ill fell into two categories. Those in the first category had suffered severe lung damage and function would not return in the short term, meaning they require ECMO support to live – at that time, Leishenshan only had one patient in this category. Patients in the second category had already recovered from the virus, but were experiencing complications such as multiple organ failure, or had underlying conditions prior to contracting the coronavirus. Covid-19 therefore induced other severe conditions such as coronary heart disease, stroke, and tumors, Peng said. 

Public statements from Hubei province’s health authorities showed that on April 14, 179 Covid-19 patients remained in Wuhan’s hospitals, 57 with acute illnesses and 33 who were critically ill. On Friday, the National Health Commission (NHC) announced that the situation had improved further: the number of patients with acute illnesses in Wuhan had fallen to zero, something perhaps unimaginable during the peak of China’s epidemic’s in mid-February, when nearly ten thousand were hospitalized. 

To concentrate medical resources in recent weeks, Hubei’s coronavirus epidemic response task force decided on April 12 to consolidate patients into facilities including Wuhan’s Tongji and Jinyintan hospitals, depending on their condition. 

On April 14, the last four severely ill patients at Leishenshan were transferred to Zhongnan Hospital. With it, the makeshift facility was retired, and Peng no longer had to go back and forth between the two locations. 

Zhongnan Hospital’s ICU now had a total of 13 patients from both Leishenshan and Jinyintan. According to officials, since it opened on Feb. 8, Leishenshan had taken in 2,011 patients, ranging from infants to people over 100 years old. A total of more than 1,900 recovered and were discharged, or roughly 94% of patients. 

The heads of ICUs that spoke to Caixin emphasized the importance of clinics that conduct screening and serve as gatekeepers. These, they say, are the real front line of the battle against Covid-19. As hospitals return to normal, they say, hospitals must make full use of their fever clinics and give full play to epidemiological investigations.