
Cartoon – The Light in the Tunnel



They have been at this for almost a year. While politicians argued about masks, superspreader weddings made the news, a presidential election came and went, and at least 281,000 Americans died, nurses reported for work. The Post asked seven ICU nurses what it’s been like to care for the sickest covid patients. This is what they want you to know.
As of Dec. 7, Idaho has seen 110,510 total confirmed cases, 1,035 deaths, and 477 people are currently hospitalized with the virus.

Our staff are getting sick. Our physicians are getting sick. And they’re not getting it from the hospital. They’re getting it from the community. We are almost lucky to care for the covid patients because we know who they are. Anytime we go into these rooms, we know exactly what we need to do. We have all the PPE we need. And as long as we are diligent and follow all the processes that are in place, we can keep ourselves safe. That’s not what worries me at all. Going out into the community is scarier than coming into work every day. Because you don’t know who has it.
This virus has caused this feeling, this sense of isolation. The covid unit is an isolated desert. Every door is shut. Every room has negative airflow. By the time you put your N95 mask on and then your surgical mask over the top of that, then you put your isolation gown on and your face shield on top of that, you can’t tell who is who. So much of health care is about that personal touch — now, our patients can’t even see our name badges because they are on under our gowns. All they see are our eyes through our face mask.
A lot of families are hesitant to have Zoom calls with patients because it can be uncomfortable and awkward. Especially if these patients are sedated and intubated. There’s always that awkwardness of: Can they hear you? Can they not hear you? Even as nurses, we feel like we’re talking to the wall. But we talk to them just as if they were awake. Allowing families to play their music that they like or pray with them or just talk to them can absolutely help. You see vital signs change.
One patient, all she wanted to do was have her son sing her a song. I think I spent over an hour in the room listening to him play the guitar and sing her a song. He sang her mostly hymns.
Death is a very intimate event that normally involves a lot of family members that help bring closure and that helps everyone process. In normal circumstances, health care providers form these relationships with the family at the bedside. All of that has been removed. And we now have to try to form those relationships over the telephone. It’s a traumatic experience. And it’s a long drawn-out process. A lot of people don’t make it out of here. It’s a slow, lonely death.
The amount of death with covid is profound. As nurses, we have learned to process death, but the amount of death has happened in such a short span of time — that’s what’s been overwhelming. I had a patient that we did a Zoom call with. His four-year-old granddaughter lived with him. And she brought tears to the room. The naivete of a four-year-old. Her grandfather was intubated so he couldn’t talk. But he could kind of look around the room. But the innocence of her, saying, “Come home, Pa. I miss you, Pa. I love you Pa,” all through a video screen. The 14-year-old that also lived with them couldn’t formulate words to say anything, and he didn’t know what to do or say in that video. But the four-year-old was telling Pa to come home.
As of Dec. 7, Mississippi has seen 166,194 total confirmed cases, 3,961 deaths, and 1,157 people are currently hospitalized with the virus.
There are some patients who have been in their younger 20s and their younger 30s, and I think maybe those are the hardest cases. They have families and they have kids just like I do, and it’s hard coming into work and taking care of them. Knowing they’re supposed to be going to college, they’re supposed to be getting married, they’re supposed to be having kids and, instead, they’re laying in a hospital bed on a ventilator fighting for their life.
They have their whole entire lives ahead of them, and then they get hit with this disease that everybody thinks is a hoax and then they die.
I worked in the ER a month ago, so I know exactly what’s going on down there, and now I work in the ICU, so I know exactly what’s going on on both sides of it. There are no ICU beds in the hospital. None. When there are no ICU beds, we hold them in the ER, or we hold them in the PACU (post-anesthesia care unit). The ER still has to treat our trauma patients, our car accidents, our gunshot victims. So when we have those ICU holds in the ER, it obviously makes the jobs of nurses and doctors in the ER way more difficult than it needs to be. We are treating patients in the hallway. They’re just trying to do the best they can with the resources that we have.
There is no room left, essentially, and I think that’s really what people don’t seem to understand. And I get it, when you’re not in health care you don’t really see our side of it, but we’re seeing the worst of it. It’s hard for us to convey that to the public because they don’t seem to want to take our word for it — but take our word for it. Take our word for it.
As of Dec. 7, Iowa has seen 244,844 total confirmed cases, 2,717 deaths, and 898 people are currently hospitalized with the virus.
I cry every day when I walk in to work, and I cry every day when I walk to my car after work.
You get it out of your system before you show up and you do your job and you’re fine. Then, you go home and you cry before you get home. And then you go home and be mom.
My 9-year-old daughter asks frequently, “Mommy, how many patients were there today? Mommy, how many sick ones were there today? Were you safe? Was everything okay? Do you have to go to work again? How many patients?” She gets it.
I think one thing that people do not appreciate is it’s not only the number or volume of patients that comes through — it’s the level of care that they require, which is so much greater than a standard patient in the ICU or a standard patient in the floor, because they can get very, very sick very quickly.
We were walking a patient who was on ECMO, which is extracorporeal membrane oxygenation, and it took five people to walk her. That’s not normal.
I work in the MICU, so it’s never like a party up in here, but it used to at least be, nine times out of ten, calm and controlled and tidy and clean. Occasionally stuff would go bad and we would all run and help, and then we would all go about our days. Now it just feels like, especially of late, there is equipment everywhere. There are gowns everywhere. There are gloves everywhere, there are people everywhere, and there are fires everywhere.
I’m actually scared, and I’ve never been scared at work before. I am scared that we will lose control.
It’s the human resources we are running low on. We can make a bed, we can find a ventilator, we have PPE. But it’s the human cost of caring for these patients that has been keeping me up at night the past couple of weeks and really making me nauseous every day.
I didn’t think it would be over by now, but I didn’t think we’d be getting hit this hard this late. I thought we’d still just be smoldering. I didn’t know that we would just be a raging fire at this point in time. We’re not prepared for that, but here we are.
After this, I’m going to take my kids to a beach or somewhere.
As of Dec. 7, Illinois has seen 796,264 total confirmed cases, 14,216 deaths, and 5,190 people are currently hospitalized with the virus.

I’ve taken care of a lot of husband-wife patients, unfortunately. One of the cases was one in which the husband had tested positive for covid first, but he was a mild case. She was a little bit more serious. She ended up on our unit.
The husband ended up in the hospital the next day, but he was on the step-down unit. When I admitted her, she was terrified, especially knowing that her husband was upstairs in another unit. She was having a hard time breathing, and she grabbed onto my hand and looked at me. She goes, “Am I gonna die?” I mean, I didn’t know what to say. And I just told her, “Not on my watch.” So we just kept on going. But unfortunately, she got intubated the next day.
Then I was sent to work upstairs on the step-down unit. I had her husband that next day, and he was actually quite happy that I saw her. He goes, “You took care of my wife, how is she? I heard that she’s not doing well.” I didn’t know what to say to him, either. I just said, “You know, she’s in the best of care. We’ll take really good care of her.” And he looked really relieved. He goes, “I’m just so glad that someone who had seen her is here now to talk to me.” And my heart broke with that.
She ended up passing. A few days after, he went home, and I didn’t see him, so I don’t know how he took it. He wasn’t able to see her before she passed.
We wear personal air purification respirators on our heads — these big white domes over our heads with a respirator hose going to a machine strapped around our waist, and we look like astronauts walking through the unit, going in and out of patients’ rooms with our plastic gowns and gloves.
It can be frightening to family members if they’re allowed to come to visit and definitely for patients because we’re kind of scary-looking. It can be frantic at times. You walk through the hall, and you see a lot of patients on ventilators. You hear a lot of beeping. People are rounding constantly to check on patients. It’s a busy place.
You don’t know what to tell family members when you see them. What can you say? You just say, “I’m sorry.” You can’t even hug them. I used to be able to hug family members, but you can’t with all the gear.
When patients are scared, I will hold their hand even though I’m wearing gloves. I look them in the eyes as much as I can because really, that’s all you can see. You can’t see our faces. You can barely even hear past the mask. So I’ll make sure to look at them. I try to make an effort to smile with my eyes and to just hold their hand if they need it.
As of Dec. 7, Utah has seen 215,407 total confirmed cases and 939 deaths.

These patients are different than the typical patient. They’re very complex. They can change in the blink of an eye. And it’s very hard as a nurse when you wrap your heart and soul into taking care of these patients. I started noticing that I was emotionally tired. I was physically completely exhausted. And I was beginning to question whether or not I could continue forward being a nurse at all. I was past my physical capacity.
I happened to be working a day where another health care worker who was a veteran said that this was like a combat zone, and for some reason in my head, that validated the way that I was feeling. So I reached out to one of my best friends who is a veteran, a flight medic, and he said, “I meditate and do yoga.”
Once I started doing that, I was able to handle the emotional crises, the physical pain of working so, so many long, hard hours. We do something called proning, where you take patients and flip them over onto their bellies. And that sounds really easy, but it takes a team of a minimum of five people. It is extremely taxing on your body. It hurts. And I lift weights! The meditation and yoga really has saved my life, my mental capacity, my spiritual capacity, my physical capacity, everything that is required to give to these patients.
Hopefully by 8 p.m., I’m out in the parking lot and spend a minute in my car to unload from my day. It’s all about taking a moment to breathe for myself and then going through whatever came up that day that I need to let go of. It depends on how complicated my patient was that day, whether I can let my whole day go or if I have to spend time to go through each piece and work it down to: What did I do right? Did I miss something? Sometimes I just can’t let some details go quickly, and I have to work them down to allow myself to say I did everything that I possibly could for this individual this day, in this time, in this situation. And whatever the outcome was or is, I followed protocol. I did everything that I knew how to do. And it’s going to be OK.
I find it very frustrating when I go out and about on my days off and I see people very blatantly not wearing masks or trying to tell me how come they don’t work or telling me that this pandemic isn’t real. I find it completely disrespectful to the work we do to save people’s lives, to have people think that this pandemic isn’t real, to show utter disregard for people around them, not trying to do their part.
And I really wish that I could take people on a day with me so that they can see what I see. So that they can feel your feet ache so bad that you wish they’d just fall off, because you’re on that concrete for so many hours. Your back aches because you’re wearing equipment to save your life — so that you can save somebody else’s life. And your head hurts. I’ve never had so many headaches in my life because part of the equipment sits on your head, and after 12 hours, it starts to exert so much pressure that you start to have a headache, and you’re dehydrated.
Early in the pandemic, I remember walking into this room, and this young patient was crying and asked me if they were going to die. And I’m a mom of teenagers. For me, that was awful because this patient was all alone, and we as staff were minimizing contact because we didn’t want to get the virus.
This patient started physically trembling in the bed. I couldn’t take it anymore, and I went over and just held this patient because that’s what I’d want somebody to do for my children. That was my first patient that I held like that. And there have been many since.
As of Dec. 7, Utah has seen 215,407 total confirmed cases and 939 deaths.

A few weeks ago, my wife and I were on a date at a restaurant. And in the middle of nowhere, I had this panic attack and went and hid in the bathroom stall for half an hour. I have no idea what brought it on. I just couldn’t handle being there right then, which was weird for me. That’s the first time anything like that has happened. But since then, it’s happened multiple times, where the anxiety and stress is overwhelming, and I can’t handle it. So I have to go and excuse myself for a little bit.
Balancing work and life is something that used to seem possible. Now it doesn’t seem like there is any difference between the two. I fall asleep and I dream about my patients.
When we got our first covid patient in February in the hospital, in the ICU, we all kind of thought it was a little bit of a joke, to be honest. I had this patient, and he was sitting there with minimal amounts of oxygen in the room just watching TV. He’s like, “I’m fine. I don’t know why everyone’s freaking out about this.” And I thought the same thing. And then a few hours later, he stands to go pee, and I’m looking at his monitor. And it drops down to the low 90s. Ninety-two is about as low as you want to go. And then it starts dropping down lower, to about the 70s. Then it gets down into the 60s and 50s. And that’s dangerous territory. That’s where brain cells start dying and you start having some serious problems.
I run into the room. We get him back into bed and throw all the oxygen that we have in the room on him, crank everything up, and he’s not recovering from it. We had to intubate right then and there. And about an hour later, he finally starts recovering a little bit. But at this point, he’s sedated, he’s on the ventilator. Everything is worse. And that’s the first time where it’s like: Oh, crap, this is serious. This is something else. I’ve never seen anything like that before.
If a patient’s heart stops or if they stop breathing, we call a code blue, and that’s when the doctor, respiratory therapist, nurses, everybody comes into the room. We start chest compressions or CPR or that kind of stuff. This one patient’s heart is not working. So I call the code blue. We all get in there. We start doing the chest compressions. Five minutes later, we get the patient back. We all go back about our work. Twenty minutes later, same thing happens again. We start doing the chest compressions. We start pushing medications as fast as we can to get the patient back again.
The spouse comes into the hospital. I explain: “Just so you know, this is what happened before. It could possibly happen again. If it does, I’m going to need you to step outside of the room.” And as I’m explaining this, sure enough, it happens again. We lose the pulse. We lose the heartbeat. So I ask her to leave the room. Everyone gets in there, and we start going for it. We went for almost two hours: chest compressions, pushing medications, shocking the patient’s heart.
The doctor is ultimately the one who makes the decision about when we stop, and they call time of death. But typically in situations like that, where it’s unexpected and sudden, they want to make sure that everybody can go home that night feeling OK about what they did, knowing that they did everything. And after an hour, he stops, turns to the room and asks: Does anyone have a problem with us stopping?
I didn’t have a problem, but then as he’s saying that, I look out the window, and the patient’s wife is just watching us. She’s been sitting out there watching us for an hour, and no one’s saying anything.
And I ask them to keep going.
So we did. We went almost for another hour after that, and we didn’t get the patient back. He ended up dying.
But I think for me, that was important — to keep going. Not because we thought we would get them back, but so that his wife would know that we did everything we could.
I still go to bed with her face kind of burned into my mind, of just seeing her sitting out there watching us, and that’s what kills me.
As of Dec. 7, Ohio has seen 475,024 total confirmed cases and 6,959 deaths.

I graduated from nursing school in May 2019. I started here at the Wexner in August. Our orientation is a 20-week program, and so I came out on my own Jan. 12, 2020. The pandemic hit us at the end of February.
In nursing school, I think your biggest fears are making med errors, or harming your patient in some way, or just not knowing how to do everything. Did I check my patient’s blood pressure before I gave this blood pressure medication, or did I give the correct dose of a specific medication? I had heard stories about that on the unit, like make sure you’re careful with the needle stick, or make sure you’re careful with this medication. And I don’t even think about those kinds of things anymore.
Now it’s the fear of the unknown. It’s the fear that anything could happen because of this virus and my patient could die regardless of what I do.
When I got my first covid-positive patient, I remember thinking: Somebody did the assignment wrong because there’s no way that they believe that I should be taking care of this patient. I can remember the feeling. I can remember the day. It was a weekend. I was on a day shift. And I was thinking to myself: Who trusted me, the new nurse to take care of a covid-positive patient? How am I going to do this? How am I going to keep this patient safe? How am I going to keep myself safe? Am I safe? Wait, who cares about me? Let’s get back to the patient. What do they need?
At the time, I didn’t even understand some of the ventilator settings because I was still that new, and it was still that fresh to me. And I thought: This machine is doing that much work for them, and I don’t know enough about it, but I’m going to make sure that I get it done and I’m going to figure it out today to make sure that this patient gets everything that they need. And I’m going to call their family and double check with them and check in with them and call them.
That patient is alive. That patient is no longer in the hospital. As far as I know, that patient is home and safe with family.
I would feel like: There’s someone more experienced. There’s someone more adequate to deal with this. And I was like — oh, it’s me. This is me, I’m doing this, and I’ve been doing it ever since.
I saw new nurses come out of orientation, and I saw the type of assignments that they would get. So my mind fixated on like: I’m going to get patients that are ready to transfer out. They can talk, they can eat. They’re just waiting for a bed on another unit. Or maybe it’s a patient who needs long-term care. So they’re waiting to go to a facility to be discharged. And so I was thinking to myself: I’m going to get my feet wet. It’s going to be great. I’m going to build up this experience, and then I’m going to start getting sicker patients, and I’m going to be ready.
Once covid hit, there was no room for those types of patients anymore. Everyone had covid, everyone was sick, everyone was intubated or approaching intubation.
And for me, I just wanted my first experience. I wanted to have the simple experience of building and getting better. But that’s not what was in store. And I can’t say that I’m upset about it today. I’m grateful for this experience. I don’t wish this pandemic on anyone. I wish it was not here. I wish that it was different. But as a nurse, as a new nurse, these experiences are unique to me. It’s making me a better nurse. It’s made me a better person, and I can only continue to just be.
We did cry in the beginning, and now not so much. I think we all struggled when we had a young death. Someone in their 20s was very difficult for us. Because you think: That was a young life. What a young life that was, and they’re not here anymore. Because of a virus. That’s hard. It’s very hard.
But now it’s just — it’s almost everyone’s story.

AstraZeneca on Monday became the third pharmaceutical company to announce remarkable results from late-stage trials of a coronavirus vaccine, saying that its candidate, developed by Oxford University, is up to 90 percent effective.
This is the third straight week to begin with buoyant scientific news that suggests, even as coronavirus cases surge to devastating levels in many countries, an end to the pandemic is in sight.
Pfizer and its German partner BioNTech and Moderna have each reported vaccines that are 95 percent effective in clinical trials. A direct comparison to the Oxford-AstraZeneca vaccine is complicated, due to the trial design, but the vaccine may be a more realistic option for much of the world, as it is likely to be cheaper and does not need to be stored at subzero temperatures.
Peter Piot, director of the London School of Hygiene & Tropical Medicine, who was instrumental in the battle against AIDS, said the positive results from three vaccine candidates cannot be overestimated.
“2020 will be remembered for the many lives lost from covid-19, lockdowns and the U.S. election. Science should now be added to this list,” said Piot, adding, “the only way to stop covid-19 in its tracks is having multiple effective and safe vaccines that can be deployed all around the world and in vast quantities.”
“I’m totally delighted,” said Hildegund C.J. Ertl, a vaccine expert at the Wistar Institute in Philadelphia. Adding to the results from Pfizer and Moderna, “what it tells me is this virus can be beaten quite easily: 90 to 95 percent efficacy is something we’d dream about for influenza virus, and we’d never get it.”
The Oxford-AstraZeneca team said in a video conference with journalists that its candidate offered 90 percent protection against the virus when a subject received a half-dose, followed with a full dose one month later. Efficacy was lower — 62 percent — when subjects received two full doses a month apart. The interim results, therefore, averaged to 70 percent efficacy.
Andrew Pollard, chief investigator of the Oxford trial, said the findings showed the vaccine would save many lives.
“Excitingly, we’ve found that one of our dosing regimens may be around 90 percent effective, and if this dosing regimen is used, more people could be vaccinated with planned vaccine supply,” he said.
Britain has preordered 100 million doses — which at a dose and a half per person would cover most of its population. The United States has ordered 300 million.
The results have yet to be peer-reviewed or published, and will be scrutinized by regulators. Many questions remain, including whether the vaccine can reduce transmission of the virus by people without symptoms, which would have repercussions for how soon people could stop wearing masks. It is also unclear how long the immunity from the vaccine lasts — a crucial question.
Sarah Gilbert, a lead Oxford researcher, cautioned that the dose-and-a-half regimen would have to be more closely studied to be fully understood. But she said the first half-dose might be priming a person’s immune system just enough, and that the second booster then encourages the body to produce a robust defense against sickness and infection.
AstraZeneca and Oxford have been conducting Phase 3 clinical trials worldwide, with the most recent data coming from an interim analysis based on 131 coronavirus infections in Britain and Brazil among 10,000 volunteers, with half getting the vaccine and half getting a placebo.
The company said it would present the results to Britain’s health-care products regulators immediately and would seek approval to fine-tune its clinical trials in the United States, to further assess the half-dose shot followed by a booster.
Because the vaccine is already in production, if approved, the first 4 million doses could be ready in December, and 40 million could be delivered in the first quarter of 2021, company executives said. By the spring, the company and its global partners in India, Brazil, Russia and the United States could be cranking out 100 million to 200 million doses a month.
British Health Secretary Matt Hancock said “should all that go well, the bulk of the rollout will be in the new year.”
In a statement to Parliament, Prime Minister Boris Johnson said that vaccines were “edging ever closer to liberating us from the virus, demonstrating emphatically that this is not a pandemic without end. We can take great heart from today’s news, which has the makings of a wonderful British scientific achievement.”
World markets have rallied on optimistic vaccine news, though shares in AstraZeneca were down Monday on the London stock exchange.
No participants who received the vaccine developed severe cases or required hospitalization, AstraZeneca said Monday. The drugmaker also said that no “serious safety events” were reported in connection with the vaccine, which was typically “well tolerated” by participants regardless of their dosing levels or ages.
The vaccine uses a harmless cold virus that typically infects chimpanzees to deliver to the body’s cells the genetic code of the spike protein that dots the outside of the coronavirus. That teaches the body’s immune system to recognize and block the real virus.
Although the reason the regimen with an initial half-dose worked better remains to be teased out, Ertl said that it could be related to the fact that the body’s immune system can develop a defense system to block the harmless virus that’s used to deliver the spike protein’s code. Giving a smaller initial dose may lessen those defenses, and make the vaccine more effective.
Several other vaccines in late-stage development use a similar technology, harnessing a harmless virus to deliver a payload that will teach the immune system how to fight off the real thing — including the Johnson & Johnson vaccine, the Russian vaccine being developed by the Gamaleya Research Institute and the vaccine made by CanSino Biologics in China.
While the results released by AstraZeneca indicate somewhat lower efficacy than Pfizer and Moderna, the vaccine can be stored and transported at normal refrigerated conditions for up to six months. That could make it significantly easier to roll out than Pfizer’s vaccine, which has to be stored at minus-70 degrees Celsius, or Moderna’s, which is stable in refrigerated conditions for only 30 days and must be frozen at minus-20 degrees Celsius after that.
The Oxford-AstraZeneca vaccine was first developed in a small laboratory running on a shoestring budget by Gilbert at Oxford and her team. The university kicked in 1 million pounds ($1.3 million) and then sought a manufacturing partner, before settling on AstraZeneca.
“We wanted to ensure there wouldn’t be any profiteering off the pandemic,” said Louise Richardson, the university’s vice chancellor, so that their vaccine would be widely distributed “and wouldn’t just be for the wealthy and the first world.”
The scientists said that although it appeared to be a race, or a competition, among the front-running vaccine developers, no one company could produce by itself the millions of doses needed to end the pandemic.
“We don’t have enough supply for the whole planet,” Pollard said, adding that the important message is that today there are at least three highly effective, safe vaccines, that also appear to work well among the elderly, and that they are produced using different technologies, ensuring the quickest route to manufacture the billions of doses that will be necessary.
Pollard said it is “unclear why” the different vaccines were producing different results, and he said he and the scientific community awaited full data sets from all the clinical trials to fully understand what is going on. He said different studies were also using different end points to describe efficacy.
“At this moment we can’t fully explain the differences,” Pollard said. “It’s critical to understand what everyone is measuring.”

Like a lot of people, I have really gotten into listening to podcasts over the last year. They’re such an immersive way to learn about the world, and I like how the format lets you dive as deep on a topic as you want. So, I was inspired to start one of my own—but I knew I couldn’t do it on my own.
I couldn’t ask for a better partner on this project than Rashida Jones. A mutual friend suggested that the two of us might have a lot to talk about, and it turned out he was right. I already knew she was a talented actor, but I was impressed by her thoughtful perspective on the world. So, we decided to start a podcast that lets us think through some of today’s most pressing problems together. In our first episode, Rashida and I explore a big question that is top of mind for many people: what will the world look like after COVID-19?
I know it’s hard to imagine right now while new cases are surging around the world, but there will come a time when the COVID-19 pandemic is behind us. I think it’s safe to assume that society will be changed forever, given how disruptive the virus has been to virtually every part of our lives.
Unfortunately, we still have a long way to go before life truly gets back to “normal.” Rashida and I were joined by Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, to discuss what to expect in the months to come. I’ve had the opportunity to work with Dr. Fauci on a number of global health issues over the years, including the quest for an HIV vaccine and cure. He’s such a quiet and unassuming guy normally, so it’s been wild to watch him become a huge celebrity.
Dr. Fauci and I are both optimistic that a vaccine will bring an end to the pandemic at some point in the near future. But what the world looks like after that is a lot less clear. I suspect that some of the digitization trends we’ve seen—especially in the areas of online learning, telemedicine, and remote work—will become a regular part of our lives. I hope this episode leaves you hopeful about the future and curious about what comes next.


Hospitalized COVID-19 patients receiving SNG001, inhaled nebulized interferon beta-1a, were more likely to show clinical improvement than those receiving placebo, a small pilot study in the U.K. found.
Patients randomized to receive SNG001 for 14 days had greater odds of improvement on the World Health Organization (WHO) ordinal scale for clinical improvement (OSCI; OR 2.32, 95% CI 1.07-5.04, P=0.033) on day 15 or 16 compared with those receiving placebo, reported Tom Wilkinson, PhD, of University of Southampton in England, and colleagues.
Moreover, patients in the intervention group were more likely to revert to an OSCI score of 1, or no limitation of activities, on day 15 or 16 (HR 2.19, 95% CI 1.03-4.69, P=0.043), the authors wrote in the Lancet Respiratory Medicine.
Type 1 interferon is “one of the first cytokines induced by viral infection of a cell and is a primary driver of innate immune responses in the human lung,” the researchers noted. They explained that SNG001 is a formulation of recombinant interferon beta “for inhaled delivery by [nebulizer],” which has been well tolerated in clinical studies among patients with asthma or chronic obstructive pulmonary disease.
Interestingly, an accompanying editorial by Nathan Peiffer-Smadja, MD, and Yazdan Yazdanpanah, MD, PhD, both of Assistance-Publique Hôpitaux de Paris in France, noted that interferon failed in preliminary results from the WHO’s SOLIDARITY trial.
In addition to different composition of the two trials, the editorialists found another key difference: route of administration. SOLIDARITY used subcutaneous interferon beta-1a, whereas this trial used nebulized therapy that “delivers interferon beta-1a directly to the respiratory tract.”
“[Nebulized] therapy allows targeted delivery of interferon to the lungs, where it can induce the expression of interferon-stimulated genes that participate directly … or indirectly … in the antiviral response in the mucosa,” Peiffer-Smadja and Yazdanpanah wrote.
For the new study, Wilkinson and colleagues randomized adults hospitalized with COVID-19 symptoms, who tested positive for SARS-CoV-2 via reverse-transcriptase polymerase chain reaction or point-of-care test to receive either SNG001 or inhaled placebo for 14 days. Primary outcome was change in clinical condition on the WHO OSCI (a 9-point scale where 0 means no infection and 8 means death).
From March 30 to May 30, a total of 48 patients were randomized to SNG001 and 50 to placebo in an intent-to-treat analysis. Patients were a mean age of 57, 59% were men, and 80% were white. Baseline comorbidities included hypertension, cardiovascular disease, diabetes, chronic lung condition, and cancer.
Demographic characteristics between groups were similar, although the SNG001 group had more severe disease, with 77% of patients receiving oxygen therapy vs 58% in the placebo group. Mean duration of symptoms before treatment initiation was 10 days.
In the SNG001 group, the odds of improvement were more than three-fold greater on day 28 versus placebo (OR 3.15, 95% CI 1.39-7.14, P=0.046), the authors noted.
Five patients underwent intubation or died compared with three in the intervention group. Over the 14 days of treatment, patients in the intervention group were more than twice as likely to recover.
There was no difference in the odds of hospital discharge or time to hospital discharge between groups. By day 14, 73% of the placebo group and 69% of the intervention group had been discharged.
Regarding safety, 54% of patients in the intervention group and 60% in the placebo group reported treatment-emergent adverse events, the most common of which was headache (15% and 10%, respectively). Fewer patients in the intervention group had serious adverse events compared with placebo (15% vs 28%), and the most common were respiratory failure (6% vs 12%) and pneumonia (6% each).
One patient in the placebo group had multiple organ dysfunction syndrome and one had pulmonary embolism, which caused them to withdraw from the study. These patients later died, along with a third patient in the placebo group, who died of COVID-19 pneumonia.
In their editorial, Peiffer-Smadja and Yazdanpanah noted that the study was not powered to assess mortality outcomes, and called for large randomized trials to investigate the effectiveness of nebulized interferon beta-1a, speculating that it might benefit patients in an early stage of disease in the outpatient setting.
“In patients with severe COVID-19, an exacerbated inflammatory response has been identified as a cause of pulmonary complications, and interferon beta-1a — a pro-inflammatory cytokine — could increase the inflammatory response and be associated with safety issues,” the editorialists wrote.
They added that safety will also be a concern, as “[nebulization] of interferon has no marketing [authorization] for any indication yet.”
Notably, COVID-19 guidelines from the National Institutes of Health recommend against the use of interferon, except within a randomized clinical trial.
https://www.yahoo.com/news/why-covid-19-kills-certain-100211975.html
Dr. Megan Ranney has learned a lot about Covid-19 since she began treating patients with the disease in the emergency department in February.
But there’s one question she still can’t answer: What makes some patients so much sicker than others?
Advancing age and underlying medical problems explain only part of the phenomenon, said Ranney, who has seen patients of similar age, background and health status follow wildly different trajectories.
“Why does one 40-year-old get really sick and another one not even need to be admitted?” asked Ranney, an associate professor of emergency medicine at Brown University.
In some cases, provocative new research shows, some people — men in particular — succumb because their immune systems are hit by friendly fire. Researchers hope the finding will help them develop targeted therapies for those patients.
In an international study in Science, 10 percent of nearly 1,000 Covid-19 patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons. These antibodies — known as autoantibodies, because they attack the body itself — weren’t found at all in 663 people with mild or asymptomatic Covid-19 infections. Only four of 1,227 healthy patients had the autoantibodies. The study was led by the Covid Human Genetic Effort, which includes 200 research centers in 40 countries.
“This is one of the most important things we’ve learned about the immune system since the start of the pandemic,” said Dr. Eric Topol, executive vice president for research at Scripps Research in San Diego, who wasn’t involved in the new study. “This is a breakthrough finding.”
In a second Science study by the same team, the authors found that an additional 3.5 percent of critically ill patients had mutations in genes that control the interferons involved in fighting viruses. Given that the body has 500 to 600 of those genes, it’s possible that researchers will find more mutations, said Qian Zhang, lead author of the second study.
Interferons serve as the body’s first line of defense against infection, sounding the alarm and activating an army of virus-fighting genes, said virologist Angela Rasmussen, an associate research scientist at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health.
“Interferons are like a fire alarm and a sprinkler system all in one,” said Rasmussen, who wasn’t involved in the new studies.
Lab studies show that interferons are suppressed in some people with Covid-19, perhaps by the virus itself.
Interferons are particularly important for protecting the body against new viruses, such as the coronavirus, which the body has never encountered, said Zhang, a researcher at Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases.
When infected with the novel coronavirus, “your body should have alarms ringing everywhere,” Zhang said. “If you don’t get the alarm out, you could have viruses everywhere in large numbers.”
Significantly, patients didn’t make autoantibodies in response to the virus. Instead, they appeared to have had them before the pandemic even began, said Paul Bastard, the antibody study’s lead author, who is also a researcher at Rockefeller University.
For reasons that researchers don’t understand, the autoantibodies never caused a problem until patients were infected with Covid-19, Bastard said. Somehow, the coronavirus, or the immune response it triggered, appears to have set them in motion.
“Before Covid, their condition was silent,” Bastard said. “Most of them hadn’t gotten sick before.”
Bastard said he now wonders whether autoantibodies against interferon also increase the risk from other viruses, such as influenza. Among patients in his study, “some of them had gotten flu in the past, and we’re looking to see if the autoantibodies could have had an effect on flu.”
Scientists have long known that viruses and the immune system compete in a sort of arms race, with viruses evolving ways to evade the immune system and even suppress its response, said Sabra Klein, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.
Antibodies are usually the heroes of the immune system, defending the body against viruses and other threats. But sometimes, in a phenomenon known as autoimmune disease, the immune system appears confused and creates autoantibodies. This occurs in diseases such as rheumatoid arthritis, when antibodies attack the joints, and Type 1 diabetes, in which the immune system attacks insulin-producing cells in the pancreas.
Although doctors don’t know the exact causes of autoimmune disease, they’ve observed that the conditions often occur after viral infections. Autoimmune diseases are more common as people age.
In yet another unexpected finding, 94 percent of patients in the study with the autoantibodies were men. About 12.5 percent of men with life-threatening Covid-19 pneumonia had autoantibodies against interferon, compared with 2.6 percent of women.
That was unexpected, given that autoimmune disease is far more common in women, Klein said.
“I’ve been studying sex differences in viral infections for 22 years, and I don’t think anybody who studies autoantibodies thought this would be a risk factor for Covid-19,” Klein said.
The study might help explain why men are more likely than women to become critically ill with Covid-19 and die, Klein said.
“You see significantly more men dying in their 30s, not just in their 80s,” she said.
Akiko Iwasaki, a professor of immunobiology at the Yale School of Medicine, noted that several genes involved in the immune system’s response to viruses are on the X chromosome.
Women have two copies of this chromosome — along with two copies of each gene. That gives women a backup in case one copy of a gene becomes defective, Iwasaki said.
Men, however, have only one copy of the X chromosome. So if there is a defect or a harmful gene on the X chromosome, they have no other copy of the gene to correct the problem, Iwasaki said.
Bastard noted that one woman in the study who developed autoantibodies has a rare genetic condition in which she has only one X chromosome.
Scientists have struggled to explain why men have a higher risk of hospitalization and death from Covid-19. When the disease first appeared in China, experts speculated that men suffered more from the virus because they are much more likely to smoke than Chinese women.
Researchers quickly noticed that men in Spain were also more likely to die of Covid-19, however, even though men and women there smoke at about the same rate, Klein said.
Experts have hypothesized that men might be put at higher risk by being less likely to wear masks in public than women and more likely to delay seeking medical care, Klein said.
But behavioral differences between men and women provide only part of the answer. Scientists say it’s possible that the hormone estrogen may somehow protect women, while testosterone may put men at greater risk. Interestingly, recent studies have found that obesity poses a much greater risk to men with Covid-19 than to women, Klein said.
Yet women have their own form of suffering from Covid-19.
Studies show that women are four times more likely to experience long-term Covid-19 symptoms, lasting weeks or months, including fatigue, weakness and a kind of mental confusion known as “brain fog,” Klein said.
As women, “maybe we survive it and are less likely to die, but then we have all these long-term complications,” she said.
After reading the studies, Klein said she would like to learn whether patients who become severely ill from other viruses, such as influenza, also harbor genes or antibodies that disable interferon.
“There’s no evidence for this in flu,” Klein said. “But we haven’t looked. Through Covid-19, we may have uncovered a very novel mechanism of disease, which we could find is present in a number of diseases.”
To be sure, scientists say the new study solves only part of the mystery of why patient outcomes can vary so greatly.
Researchers say it’s possible that some patients are protected by previous exposure to other coronaviruses. Patients who get very sick also may have inhaled higher doses of the virus, such as from repeated exposure to infected co-workers.
Although doctors have looked for links between disease outcomes and blood type, studies have produced conflicting results.
Screening patients for autoantibodies against interferons could help predict which patients are more likely to become very sick, said Bastard, who is also affiliated with the Necker Hospital for Sick Children in Paris. Testing takes about two days. Hospitals in Paris can now screen patients on request from a doctor, he said.
Although only 10 percent of patients with life-threatening Covid-19 have autoantibodies, “I think we should give the test to everyone who is admitted,” Bastard said. Otherwise, “we wouldn’t know who is at risk for a severe form of the disease.”
Bastard said he hopes his findings will lead to new therapies that save lives. He noted that the body manufactures many types of interferons. Giving patients a different type of interferon — one not disabled by their genes or autoantibodies — might help them fight off the virus.
In fact, a pilot study of 98 patients published Thursday in the Lancet Respiratory Medicine journal found benefits from an inhaled form of interferon. In the industry-funded British study, hospitalized Covid-19 patients randomly assigned to receive interferon beta-1a were more than twice as likely as others to recover enough to resume their regular activities.
Researchers need to confirm the findings in a much larger study, said Dr. Nathan Peiffer-Smadja, a researcher at Imperial College London who wasn’t involved in the study but wrote an accompanying editorial. Future studies should test patients’ blood for genetic mutations and autoantibodies against interferon to see whether they respond differently from others.
Peiffer-Smadja said inhaled interferon may work better than an injected form of the drug because it’s delivered directly to the lungs. While injected versions of interferon have been used for years to treat other diseases, the inhaled version is still experimental and not commercially available.
And doctors should be cautious about interferon for now, because a study led by the World Health Organization found no benefit to an injected form of the drug in Covid-19 patients, Peiffer-Smadja said. In fact, there was a trend toward higher mortality rates in patients given interferon, although the finding could have been due to chance. Giving interferon later in the course of disease could encourage a destructive immune overreaction called a cytokine storm, in which the immune system does more damage than the virus.
Around the world, scientists have launched more than 100 clinical trials of interferons, according to clinicaltrials.gov, a database of research studies from the National Institutes of Health.
Until larger studies are completed, doctors say, Bastard’s findings are unlikely to change how they treat Covid-19.
Dr. Lewis Kaplan, president of the Society of Critical Care Medicine, said he treats patients according to their symptoms, not their risk factors.
“If you are a little sick, you get treated with a little bit of care,” Kaplan said. “You are really sick, you get a lot of care. But if a Covid patient comes in with hypertension, diabetes and obesity, we don’t say: ‘They have risk factors. Let’s put them in the ICU.'”
https://mailchi.mp/f2794551febb/the-weekly-gist-october-23-2020?e=d1e747d2d8
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In Thursday’s second and final Presidential debate, former Vice President Joe Biden warned that a “dark winter” lies ahead in the coronavirus pandemic, and with cases, hospitalizations, and deaths on the rise across the country, it now appears that we are headed into a “third wave” of infections that may prove worse than both the initial onset of COVID on the coasts and the summertime spike in the Sun Belt.
Yesterday more than 71,600 new cases were reported nationwide, nearing a late-July record. Thirteen states hit record-high hospitalizations this week, measured by weekly averages, most in the Midwest and Mountain West. Several Northeastern states, which had previously brought the spread of the virus under control, also experienced substantial increases in infections, leading schools in Boston to suspend all in-person instruction. Of particular concern is hospital capacity, which is already being strained in the more rural areas now being hit by COVID cases. With infection spikes more geographically widespread than in earlier waves, fewer medical workers are available to lend support to hospitals in other states, leading to concerns about hospital staffing as admissions rise.
As hospitalizations increase, so too will demand for therapeutics to help shorten the course and moderate the impact of COVID. This week, Gilead Sciences’ antiviral drug remdesivir, previously available under an Emergency Use Authorization (EUA) from the federal government, became the first drug to win full approval from the Food and Drug Administration (FDA) to treat patients hospitalized with COVID-19. The approval was based on clinical studies that showed that remdesivir can reduce recovery time, and also includes use for pediatric COVID patients under the age of 11.
Meanwhile, the FDA cleared AstraZeneca to resume US clinical trials of its coronavirus vaccine, which had been suspended for a month following an adverse patient event. It’s widely expected that one or more drug companies will submit their vaccine candidates for EUA sometime next month, although new polling data released this week indicates that the American public is growing more skeptical in their willingness to take an early vaccine against the virus, with only 58 percent of respondents saying they would get the shot when it first becomes available, down from 69 percent in August. (Only 43 percent of Black respondents say they would get the vaccine, compared to 59 percent of Whites—a racial divide that reveals deep distrust based on the history of inequities in the US healthcare system.)

In many respects, the coming month will surely prove to be a pandemic turning point, revealing the magnitude of the next wave of COVID, the direction of US public health policy, the prospects for reliable therapeutics, and the timing of a safe and effective vaccine. We’ll soon know whether we are, indeed, headed for a winter of darkness.