COVID 4
Rick Hodes, MD, MACP
JDC-Ethiopia
EthiopianSpines@gmail.com
20 April, 2020
To my Ethiopian colleagues:
I am writing to give a small update about coronavirus.
As the situation has improved a bit in New York, other areas of the United States, such as Los Angeles, are getting worse. There is an ongoing discussion about reopening the United States in various places, but that is hampered by limited testing and limited contact tracing. In addition, there is fear of a 2ndwave of disease.
The 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1) epidemics in America had 2 waves (11). The 1918 (H1N1) influenza epidemic (probably avian in origin) had 3 waves.
1) 1918 Influenza epidemic
In the 1918 influenza epidemic, between 50 and 100 million people died worldwide, and 500 million (1/3 of the world) were infected. There were 3 waves of disease: early in 1918, the last months of 1918, and again in 1919. Mortality in the second wave was about 3x worse than the first wave; people who developed illness in the first wave were protected in the 2ndwave. By the time the third wave hit, there had been “antigen drift” and previous infection was not protective. Between 2.5% and 5% of the world’s population died, including 21-71% of pregnant women who were infected. Unlike this epidemic, the peak age of death was 27 (3), but there was also high mortality in those <5 and >65 (12). It had a “W-shape” curve.
There is a debate over actual cause of death in 1918 patients. Expert John Barry believes that about 1/3 died of ARDS, and 2/3 died of secondary bacterial pneumonia (3).
In Ethiopia, this is still known as the “Hedar Beshita,” and 26 year old Tefari Mekonnen, (future Haile Selassie), contracted the disease. It is believed that 10,000 residents of Addis Ababa died, including the majority of physicians, and up to 50,000 Ethiopians perished (4,5). In Ghana 100,000 died.
2) Characteristics of the COVID-19 disease in New York: first admitted patients
Analysis of the first 393 patients (age 18+) admitted from 5-27 March at 2 academic hospitals. The average age was 62, 60.6% were male, 36% had obesity (1). In New York, 22% of the population is obese (2).
Presenting symptoms:
Cough 79.4%
Fever 77%
Dyspnea 57%
Myalgas 24%
diarrhea 24%
nausea + vomiting 19%
33.1% (130 people) were put on ventilators. As of about 17 April, only 40 patients (10.2%) were extubated, 40 patients (10.2%) died, and 66.2% (have been discharged. 23.7% had incomplete outcome data.
Smoking did not seem a risk factor. 17/128 (13.3%) of intubated patients required new renal dialysis. This is a great concern.
What we have learned:
a) Kidney disease:
A Chinese study found that 43.9% of patients had proteinuria, and 26.7% had hematuria, and 14.4% had elevated creatinine on admission. Acute kidney injury developed in 5.1% (1,7,8).
The 13.1% rate seems too low. Yesterday a senior academic physician in New York told me that 26% of his ICU COVID-19 patients were on dialysis, they have a major shortage of dialysis machines, and they are forced to share machines between 2 patients.
The renal pathology is not known. An academic nephrologist I consulted said “This is probably part of the cytokine surge leading to an ATN (acute tubular necrosis). In other cases it’s probably volume mediated - either dehydration from the diarrhea and insensible losses from the fever. Alternatively, cardiorenal pathophysiology in some patients may be occurring.” The natural history is not yet known. If ATN, it may resolve after days or weeks of renal dialysis. See the NYTimes article attached (8).
b) Promising treatment: Remdesivir:
The University of Chicago discussed their experience in an internal webinar, which has not yet been published. They recruited 125 patients (113 severe), none of whom needed a ventilator at presentation (that was exclusionary criteria). They were given daily remdesivir IV, up to 10 days as needed. They had only 2 deaths, and many were discharged by day 6. There is an ongoing NIH blinded trial of remdesivir, which should give more decisive data. Another study of 400 patients “locked” their data on 16 April, and it is now in analysis (6)
c) Unpromising treatment: hydroxychloroquine
While politicians and TV doctors are calling this a “game changer,” 3 physicians I have spoken with who are actually treating patients daily, do not think it works. Furthermore, a preprint of a meta-analysis of 11 studies also showed lack of efficacy (9). When combined with azithromycin, you have 2 drugs, which prolong the Q-T interval and can potentially cause dangerous arrhythmia.
c) Children:
In the US, 2% of confirmed COVID-19 cases were age <18. In China that number is 2.2%, in Italy, 1.2% (10).
Why the low rate? I have heard 2 possibilities: a) children have more viral immunity in general, which may help here, or b) the SARS-CoV-2 spike (S) glycoprotein binds to the cell membrane protein angiotensin-converting enzyme 2 (ACE2) to enter human cells. It has been proposed that children have less developed ACE2 binding sites. I will address the topic of possibly asymptomatic spread in the future. I have not yet come to an understanding.
d) Proning:
Everyone I have spoken with recommends this, and report that it may prevent the need for intubation. They usually favor a trial of proning before intubation.
At Columbia University, there is a dedicated “Proning team,” to teach and promote this, composed of nurses, respiratory therapists, and physical therapists.
Here is the Nebraska “pronocol” for proning: https://www.nebraskamed.com/sites/default/files/documents/covid-19/proning-protocol.pdf
Here is an instructional video on proning:
https://www.youtube.com/watch?v=E_6jT9R7WJs
Here is a proning checklist:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496747/
e) Covering all COVID-19 patients with antibiotics:
There seems to be no standard of care here.
Resources for medical personnel:
Excellent refresher on critical care issues for non-ICU clinicians
https://covid19.sccm.org/nonicu.htm
Excellent searchable resource of data published and guidelines
https://infectioncontrol.ucsfmedicalcenter.org/covid-kb
Excellent resource of treatment strategies
https://covid.idea.medicine.uw.edu/
Lastly, I want to commend my Ethiopian colleagues for their care and dedication. I am open to any questions you may have.
Sincerely,
Rick
Rick Hodes, MD, MACP
JDC-Ethiopia
EthiopianSpines@gmail.com
References:
1) Goyal P, Choi JJ, Pinheiro LC, et al: Clinical characteristics of COVID-19 in New York City. NEJM 17 April, 2020, p.
2) https://www1.nyc.gov/site/doh/health/health-topics/obesity.page
3) Barry J: the Great Influenza: the story of the deadliest pandemic in history, Viking Books, 2004
4) Pankhurst R: A historical note on influenza in Ethiopia. Medical History 1977; 21:195-200.
5) Yayehyirad Kitaw, Mirgissa Kaba: A Century after Yehidar-beshita (The Spanish Flu in Ethiopia): are we prepared for the next pandemic? Ethiopian Journal of health Development, January 1918; 32(1): 59-62
7) Cheng Y, Luo R, Wang K: Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney International 2020; March 20.
8) https://www.nytimes.com/2020/04/18/health/kidney-dialysis- coronavirus.html?searchResultPosition=1
9) https://www.medrxiv.org/content/10.1101/2020.04.13.20064295v1
10) https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html
11) Mummert A, Weiss H, Long, LP, et al: A perspective on multiple waves of influenza pandemics. PloS One 2013 Apr 23;8(4):e60343. doi: 10.1371/journal.pone.0060343. Print 2013.
12) https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html
An Overlooked, Possibly Fatal Coronavirus Crisis: A Dire Need for Kidney Dialysis
New York Times, 18 April, 2020
Ventilators aren’t the only machines in intensive care units that are in short supply. Doctors have been confronting an unexpected rise in patients with failing kidneys.
By Reed Abelson, Sheri Fink, Nicholas Kulish and Katie Thomas
For weeks, U.S. government officials and hospital executives have warned of a looming shortage of ventilators as the coronavirus pandemic descended.
But now, doctors are sounding an alarm about an unexpected and perhaps overlooked crisis: a surge in Covid-19 patients with kidney failure that is leading to shortages of machines, supplies and staff required for emergency dialysis.
In recent weeks, doctors on the front lines in intensive care units in New York and other hard-hit cities have learned that the coronavirus isn’t only a respiratory disease that has led to a crushing demand for ventilators.
The disease is also shutting down some patients’ kidneys, posing yet another series of life-and-death calculations for doctors who must ferry a limited supply of specialized dialysis machines from one patient in kidney failure to the next. All the while fearing they may not be able to hook up everyone in time to save them.
It is not yet known whether the kidneys are a major target of the virus, or whether they’re just one more organ falling victim as a patient’s ravaged body surrenders. Dialysis fills the vital roles the kidneys play, cleaning the blood of toxins, balancing essential components including electrolytes, keeping blood pressure in check and removing excess fluids. It can be a temporary measure while the kidneys recover, or it can be used long-term if they do not. Another unknown is whether the kidney damage caused by the virus is permanent.
“The nephrologists in New York City are going slightly crazy making sure that everyone with kidney failure gets treatment,” said Dr. David S. Goldfarb, chief of nephrology at the New York campus of the New York Harbor VA Health Care System. “We don’t want people to die of inadequate dialysis.”
“Nothing like this has ever been seen in terms of the number of people needing kidney replacement therapy,” he said.
Outside of New York, the growing demand nationwide for kidney treatments is fraying the most advanced care units in hospitals at emerging hot spots like Boston, Chicago, New Orleans and Detroit.
Kidney specialists now estimate that 20 percent to 40 percent of I.C.U. patients with the coronavirus suffered kidney failure and needed emergency dialysis, according to Dr. Alan Kliger, a nephrologist at Yale University School of Medicine who is co-chairman of a Covid-19 response team for the American Society of Nephrology.
Hospitals’ “usual supplies are very quickly running out,” he said.
One doctor in New York City, who was not authorized to speak publicly, recalled anguished exchanges with other physicians last week. “You’re yelling at them. You’re telling them you don’t have a dialysis machine to give them. You hear the intensity and the desperation in the other person’s voice,” the doctor said. “My job was hell.”
As the coronavirus spread rapidly in New York and in other cities, governors and mayors clamored for thousands more ventilators. But doctors have been surprised by the scarcity of dialysis machines and supplies, especially specialized equipment for continuous dialysis. That treatment is often used to replace the work of injured kidneys in critically ill patients.
The shortages involved not only the machines, but also fluids and other supplies needed for the dialysis regimen. Having enough trained nurses to provide the treatment has also been a bottleneck. Hospitals said they have called on the federal government to help prioritize equipment, supplies and personnel for the areas of the country that most need it, adding that manufacturers had not been fully responsive to the higher demand.
The fluids needed to run the dialysis machines are not on the Food and Drug Administration’s watch list of potential drug shortages, although the agency said it was closely monitoring the supply. The Federal Emergency Management Agency described the shortage of supplies and equipment as “unprecedented,” and said it was working with manufacturers and hospitals to identify additional supplies, both in the United States and overseas.
“Everybody thought about this as a respiratory illness,” said Dr. David Charytan, the chief of nephrology at N.Y.U. Langone Medical Center. “I don’t think this has been on people’s radar screen.”
The supplies allocated by manufacturers are insufficient, Dr. Charytan said, adding that the hospital switched to another type of machine when it couldn’t get additional equipment it had wanted. “It just doesn’t come anywhere close to meeting the need,” he said.
Early reports out of China suggested a low incidence of kidney damage from Covid-19, although there were some indications that the virus might directly affect the kidneys. As more data emerged from there, and as the pandemic began to take hold in Italy, word began to filter out to the broader nephrology community that many of the most seriously ill patients, those on ventilators, would also require dialysis.
It’s not yet known whether the organ injury results from the virus infecting kidney cells or is a secondary effect of critical illness or the increased tendency for blood clots to form in people with the disease.
The volume of patients needing dialysis is “orders of magnitude greater than the number of patients we would normally dialyze,” said Dr. Barbara Murphy, who is the chair of the department of medicine at Mount Sinai Health System. At her hospital alone, the number of patients requiring dialysis has risen threefold, she said.
The shortages in the United States highlight a lack of planning among state and federal officials to ensue that “hot spots like New York are given preferential access given the sheer volumes,” Dr. Murphy said.
Dr. Murphy said areas of the country that are planning for a possible surge in the demand for ventilators “also need to think about dialysis” and a national distribution system.
Hospitals are now pleading with the major manufacturers to send more supplies. As the coronavirus reached the United States, Baxter and NxStage, owned by Fresenius, placed limits on what hospitals could order to prevent hoarding.
Dr. Michael J. Ross, the chief of the nephrology division at Montefiore Health System in New York, said he spoke on the phone last Sunday with leaders of a company that produces dialysis supplies, “expressing how critical a situation this was for our patients.”
The call was about getting more machines, filters, pre-mixed fluids and tubing for continuous dialysis, he said.
The shortage of dialysis supplies in New York City hospitals was first reported by Politico.
The two main manufacturers of equipment and supplies for dialysis said orders were up fivefold, and that they were ramping up manufacturing as well as sending equipment and nursing staff to the New York region. Baxter, which is based in Illinois, said it also saw an increase in demand from China and Europe, and was flying in extra products from Europe this weekend.
“The demand spike was so fast and so high,” said Lauren Russ, a spokeswoman for Baxter. “We’re doing everything we possibly can.”
On Friday, Fresenius announced it was creating a national supply of machines that can be moved from place to place. “We are committed to supporting hospitals with continuous supply, particularly in markets most heavily impacted, so that patients can get the care they need,” said Bill Valle, the chief executive of Fresenius Medical Care North America in Massachusetts, in a statement.
Gov. Andrew M. Cuomo of New York was asked at his briefing on Thursday about hospital reports indicating that dialysis machines were in short supply. Dr. Howard Zucker, the state’s health commissioner, said “there are not shortages across the board,” and Mr. Cuomo said that hospitals in need of equipment would get it.
In a statement, José E. Almeida, Baxter’s chief executive, said that the company was trying to prioritize the delivery of products “where they are most needed — hospitals that are being overwhelmed by an influx of patients who are critically ill from Covid-19.”
At Columbia University Irving Medical Center, Dr. Donald Landry, the chair of medicine, directly contacted Mr. Valle of Fresenius when other efforts failed and the situation grew desperate. While Dr. Landry said he was appreciative that the company responded by sending more machines, supplies and dialysis nurses, he described the experience as a warning to better prepare. “New York City gave us a glimpse of when a system comes up right to the edge,” he said.
Dr. Joshua Rosenberg, an attending physician in the intensive care unit at The Brooklyn Hospital Center, said on Thursday that he was seeing acute kidney injury in a wide range of patients, beyond those who were predisposed to kidney disease because they had high blood pressure or diabetes.
Miriam Figueroa, a dialysis nurse at the hospital, went from patient to patient on Thursday, providing three-hour dialysis treatments in a Covid-19 intensive care unit set up in a former chemotherapy infusion unit.
Some patients in the I.C.U. had developed acute kidney injury. They were receiving emergency dialysis through a vein in the neck, including one hospital staff member.
Ms. Figueroa said that as the need for dialysis for critically ill patients increased, the dialysis service had coped by moving machines and supplies from outpatient clinics to the inpatient wards. “We have to pull machines to do bedside” dialysis, she said, “so there are less patients that can be done as an outpatient.”
More than a dozen of the hospital’s roughly 240 patients in its outpatient dialysis clinic have died of Covid-19, according to Dr. Priyanka Singh, one of the attending nephrologists. People with chronic kidney disease may be particularly vulnerable.
Doctors are also employing alternative types of dialysis.
Some New York hospitals, including N.Y.U., Montefiore and Weill Cornell, that are in short supply of the more specialized dialysis machines — needed for what is known as continuous renal replacement therapy — have turned to peritoneal dialysis. It is typically used in patients with chronic kidney disease who want to treat themselves at home. The treatment is not always optimal in hospital patients, especially in those whose conditions are less stable, but “we are trying to give patients something,” Dr. Charytan said.
One problem with peritoneal dialysis in the context of Covid is that it requires putting a catheter in a patient’s abdomen. That makes it difficult to use in those with failing lungs who need proning, a technique in which patients are rolled onto their stomach to help them take in oxygen. Some hospitals, including Montefiore, are placing the catheter toward the patient’s side to help with the problem.
Some hospitals are also struggling to find enough nurses and technicians to provide dialysis, especially after some who were most skilled at providing the therapy fell sick with the virus themselves. “We did lose nurses to illness,” Dr. Murphy of Mount Sinai said. “We’re just getting some of those nurses back, but it’s been a challenge. We’ve exhausted every avenue that we have within the state with regards to being able to increase nursing.”
Doctors say they are wrestling with how to ensure that patients who require immediate care receive it while assessing whether others can wait.
“Now we have to think harder about whether or not that patient truly needs it and can we manage them medically without dialysis another day so we can provide dialysis to someone who more urgently needs dialysis,” Dr. Ross of Montefiore said. “Those are not decisions we like to make.”