A Tale of Two Covids

News about Covid and the pandemic have been out of the headlines for months. The last post on this blog was August 2022. There are still plenty of people getting sick with Covid and dying but cases have generally been declining. It has become more difficult to get statistics. A lot of organizations and websites that used to update information daily stopped carrying Covid news. Case counts became unreliable in 2022 since many people were not being tested and public health does not have a record of those who test at home with a rapid test kit. The most effective way to gauge the spread of Covid is through hospital admissions and death counts, statistics that are backed by records and are fairly reliable. 

In the US, the New York Times still maintains a fairly comprehensive  Covid page with national graphs and statistics and breakdowns by state. Their summary page shows the strong downward trend in daily Covid hospital admissions after a bit of a winter peak in January 2023. Note that the breakdown by ages shows that the rate for people 70+ is four times the daily average for All ages.

Track Covid-19 in the U.S.: Latest Data and Maps

In Canada I’ve relied on Public Health Ontario for hospital admissions and death counts (other provinces may maintain similar statistics). The weekly hospital admissions in Ontario for the last year shows a strong downward trend.

https://www.publichealthontario.ca/en/data-and-analysis/infectious-disease/covid-19-data-surveillance/covid-19-data-tool?tab=tren

Covid was back in the headline news recently. On May 4, 2023 the World Health Organization WHO declared that:

Covid-19 is over as a global health emergency. Even though worldwide, someone dies of Covid every three minutes, the downward trend of the pandemic with population immunity increasing from vaccination and infection, mortality decreasing and the pressure on health systems easing has allowed most countries to return to life as we knew it before Covid-19. This means that it is time for countries to transition from emergency mode to managing Covid-19 alongside other infectious diseases.
WHO declares end to Covid global health emergency

Although the WHO declaration just confirmed what many countries had been doing in reducing various health and financial supports for the pandemic, the timing of this announcement proved to be very ironic for us. About a week later, after having stayed healthy throughout the whole pandemic, we succumbed to a Covid home invasion.

Covid Case 1

On the evening of Mother’s Day May 14, my wife N said she had a bit of a sore throat. The next day it was more persistent, but without additional symptoms it did not warrant doing a Covid test. However, the following day she woke up with a really congested sinus, a headache and she was very tired. A rapid test revealed that she was positive for Covid. N was up to date on her Covid vaccinations but “breakthrough” cases of the Omicron variant that infected vaccinated people had become common and was a big part of the reason that there was a large Omicron wave in the winter of 2022.

The incubation period for Omicron is 2.5 – 4.6 days. Counting backwards this number of days from Sunday night, the most likely event that would have exposed N to Covid in that period was the day that she had returned to an in person class. With the decreasing Covid cases we felt that it was safe enough to attend more in person events after three long years of zooming.
COVID-19 Omicron Variant of Concern and Communicability

It was still very early in the Covid infection cycle. Because of her age N would qualify for an antiviral, which must be given within 5 days of the first symptoms to be effective. She called up our local pharmacy and after a short screening questionnaire with the pharmacist, she was approved for Paxlovid. It was ready for pick up in an hour. 

Paxlovid was developed by Pfizer in record time based on some earlier work they had done on SARS (severe acute respiratory syndrome), the 2003 outbreak that was caused by a new coronavirus. They were convinced that a protease inhibitor would prevent a coronavirus from replicating. They synthesize hundreds of unique chemical compounds and then tested them against the Covid virus in the lab.
How Pfizer developed a COVID pill in record time

The clinical trial that supported the FDA approval for Paxlovid in Dec 2021 had an 89% reduction in the risk of hospitalization and death in unvaccinated people. A later real-world study showed that people who received Paxlovid had a 51% lower hospitalization rate.
Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19

N got a package of Paxlovid, 3 pills taken twice a day for 5 days. In a few days she began to feel better and the Covid symptoms were less severe, but there were side effects from the Paxlovid. She found it hard on the stomach and had some back muscle pain.

Covid Case 2

N had started to self isolate. She confined herself to the bedroom and her office and used other rooms, like the kitchen, wearing a mask and only when no one else was there. We also opened windows in most of the rooms for improved ventilation. I moved out of the bedroom into the spare room but it was all too little too late. Omicron is incredibly contagious and two days after N had tested positive I woke up with a headache and a real cold. As expected, I tested positive for Covid.

I am immunocompromised and so at high risk. My immune system is compromised and not as effective in detecting and attacking disease as in a person who has a well functioning immune system. 

There are many different reasons that someone may become immunocompromised. In my case it’s because I have multiple myeloma, a blood cancer. Although it has been well controlled with different medications over the years, the cancer as well as the treatments suppress my blood counts and my immune system. Most of my levels in a complete blood count (CBC) are below normal, from red blood cells to white blood cells, as are all of the important components of the immune system, from B cells to T cells. Although blood cancer patients are severely immunocompromised, the people who are most severely immunocompromised are transplant patients who have to take immunosuppressant drugs to prevent their immune system from attacking the foreign transplanted tissue. 

Immunocompromised people are more susceptible to all kinds of infections. People with blood cancer do not die from the cancer itself. Generally they die from an infection that overwhelms their immune system. Even pneumonia which a normal person can recover from, perhaps with the help of an antibiotic, is the cause of death for many people with blood cancer.

In addition, people who are immunocompromised do not mount a very strong immune response to the Covid vaccine. A vaccination is not an injection of antibodies that will then protect you from disease or infection. Rather, a vaccination is designed to stimulate your immune system to produce antibodies which are created by white blood cells and then circulate in your blood to attack a specific virus. With a weak immune system you don’t generate very many antibodies. After my fourth Covid vaccination I got a blood test to measure my level of Covid antibodies and it was lower than most people had after only their first vaccination. So for all intents and purposes I had been negotiating the coronavirus pandemic as an unvaccinated person. 

I checked in with my hematologist at Princess Margaret Cancer Center and she directed me to the hospital Covid Clinic. A telephone screening with a nurse practitioner recommended remdesivir, the second of the two Covid antivirals available in Ontario, because the blood thinner that I take for atrial fibrillation (afib) was a contraindication for Paxlovid. Remdesivir also had impressive clinical results, reducing the risk of hospitalization by 87%. It has fewer side effects than Paxlovid, but it can only be given as an intravenous (IV) infusion over 3 days.

Remdesivir was originally developed to treat hepatitis C and was subsequently investigated for Ebola virus disease. It wasn’t very effective for either of them.

In 2007 Dr. Mark Denison discovered that coronaviruses have a “proofreading” system. He and some other experts thought it might be possible to trick a virus with a drug that dodged the proofreading system and blocked the virus’s growing RNA chain, making it terminate prematurely. Denison learned that Gilead Sciences had dozens of drugs that might do this. In a series of lab tests, most worked to shut down coronaviruses. One of the best was remdesivir. “I like to call it the Terminator,” Denison said.
How Remdesivir, New Hope for Covid-19 Patients, Was Resurrected

With the COVID-19 outbreak spreading rapidly and a lack of alternative therapeutics, the first clinical trials using remdesivir were begun in China in February 2020. As Covid-19 began to grow into a pandemic, many scientists realized that remdesivir might be the best solution at hand. It had already undergone animal testing and safety testing in humans. So doctors began giving it to patients in studies without controls and even outside of studies altogether. Anecdotes fueled demand. Gilead sponsored some of these studies and gave the drug to doctors who treated hundreds of patients under compassionate use, a legal exemption permitting use of an unapproved drug to treat patients. In May 2020 the FDA issued Emergency Use Authorization (EUA) for remdesivir.

Gilead had flown their entire stock of remdesivir left over from Ebola research to its filling plant in California in February. They began working on restarting remdesivir production in their manufacturing plant in Edmonton and finished the first new batch of remdesivir in April 2020.
Gilead Drug Remdesivir: Rare Example of Foresight in the Pandemic

Full FDA approval for remdesivir was given in Oct 2020, the first drug approved for Covid. However clinical trial results were not that strong and some trials did not show any real benefit. The approval of remdesivir was very controversial.
The bad look of remdesivir, the first FDA-approved COVID-19 drug

In January 2022 the FDA expanded the indication for remdesivir to include its use in non-hospitalized adults. Used much earlier in the Covid infection cycle instead of only with patients sick in hospital, remdesivir had impressive clinical trial results comparable to Paxlovid, reducing the risk of hospitalization by 87%.
FDA Takes Actions to Expand Use of Treatment for Outpatients with Mild-to-Moderate COVID-19

To get started on my remdesivir infusion, the nurse said she would get someone to call me to make arrangements. I received a call back a short time later from an administrator who said there were two hospitals in Toronto where I could go. The closest one had time slots for the following morning. I was a bit flabbergasted; in a large city the size of Toronto that has about 30 hospitals, were there only two that were able to deliver a simple intravenous infusion? 

I was anxious to get started as soon as possible so I told the administrator that the second hospital was not that much further and I would prefer to go there if I could get started that day. She called back a little while later and said that this second hospital did not have any openings until the following day but she had found out that the first hospital would be able to take me if I could get there in an hour. I replied that it would be no problem. I had just finished my lunch and so I headed out. 

I drove down to Women’s College Hospital in downtown Toronto in good time. The hospital had had a major reconstruction a few years earlier and it looked like a gleaming new, modern facility. It had the best parking of any hospitals I’ve ever been to; right in the building with a short elevator ride up to the main lobby. I went to the Ambulatory Care Clinic. It was very quiet. I didn’t have to wait too long to be shown into a treatment room. On my way down the hall I saw only one other patient and otherwise not a soul. This was really kind of unexpected. The Canadian news had been full of reports about the shortcomings of healthcare budgets and services for many months. Yet here was this practically brand new hospital that seemed kind of empty. Were people having trouble finding this hospital? It was around a quiet corner on a small back street but it wasn’t that hard to find.

A nurse came in dressed in full PPE (Personal Protective Equipment) with gown, mask, visor and gloves. She gave me an information sheet on remdesivir and explained the procedure. It was going to be a 1 hour infusion followed by a 30 minute flush and observation for side effects. She proceeded to set up the IV, a small plastic tube, a catheter, that is inserted into the vein with a sharp needle. Then the needle is removed with a quick spring release, leaving the catheter inside the vein. After flushing the line with saline solution to make sure that fluid will flow through the line into the vein, she connected the valve at the end of the catheter to the tubing that was connected to the bag of fluid containing the medication on an IV stand. 

Meanwhile a young doctor came in to see if I had further questions. I asked if they had been administering remdesivir to many patients. She said that they were not very busy and in fact many of their Covid activities were being curtailed or shut down as budgets for Covid were expiring and were not being renewed.

I lay back on the bed waiting for the nurse to come back and start the infusion. When she returned she apologized for the delay and said that their pharmacy no longer prepared this drug so she had to mix it herself and it took some time for it to dissolve properly. After checking my vital signs – temperature, blood pressure, oxygen – she started the infusion. 

During this time I received a call from Home Care to arrange the next two infusions as they would not be done in the hospital. I had initially been told that because of budget cuts Home Care would not actually come to your home if you are ambulatory and instead you would have to go to a public health care clinic. However, when I spoke to them to confirm a time, they informed me that in fact for this treatment they would send out a nurse to my home. We arranged a time for the following afternoon. 

When the infusion and flush were completed, the nurse removed the tubing but left the IV line in my arm and wrapped it carefully in gauze so that it could be used again on subsequent days without having to do another needle insertion. Even though I had basically been lying in a bed for a couple hours and actually dozed off a few times, I was pretty tired. I was lucky to just miss the peak of rush hour on my drive back home. When I walked in the door it was almost 5 hours since I had left for the 90 minute treatment.

After a real nap, when I got up there was a message on my phone. It was from some pharmaceutical company who said that they would be delivering medical supplies that evening up until 11:30 p.m. At 10:00 p.m. I was pretty tired and ready for my night time sleep. I turned on the outside light and asked N to wait up and answer the door for the medical delivery. 

The next morning when I woke up I was feeling about the same. I wasn’t really expecting to see a big improvement after just one treatment but at least I wasn’t feeling worse. I hoped that was an indication that the Covid infection was not advancing. I did have a little more chest congestion but I think it was an overnight accumulation. I took some Robitussin Cough Control which was quite effective in loosening some of the mucus and phlegm buildup in my chest and later in the morning I started to feel a bit better.

Downstairs I found that three packages had arrived. One box had the medicine, one box contained all kinds of hospital equipment: syringes, various types of intravenous lines, alcohol cleaning pads, packages of sterile gauze and various other items. Wrapped up in a long package was what I guessed was the IV stand, a pole to hold the IV bag.

In the afternoon the nurses arrived in full PPE dress. It was actually two nurses because one was in training. They came into my office room and checked all the medical supplies that had arrived. Everything seemed to be in order. 

I asked the nurse if she had administered remdesivir before. She said no but the instructions were pretty straightforward. She took the bottle of remdesivir and extracted it into a large syringe and verified the volume. Then she added another liquid into the syringe and finally injected the contents of the syringe into an IV bag that was prefilled with saline solution. Unlike what I understood had been done in the hospital, this drug was mixed from liquid not from a powder and so there was no waiting time for it to dissolve. 

Meanwhile the nurse trainee had set up the IV pole. It was a simple pole that was made from cardboard, the kind you find on the inside of a roll of paper towel or toilet paper, but somewhat heavier. It was designed to be disposable so that after being used in an environment where there was an infectious disease such as Covid, it could be easily and safely discarded. 

After setting up the tubing and connecting it to the IV line in my arm, the nurse simply adjusted the valve for the right drip amount. Unlike an IV in the hospital, this IV had no pump and it was going to work strictly by gravity feed. That’s the reason that I think that the IV pole was so high.

Here’s a picture of my private hospital with my two nurses in attendance.

On Sunday I woke up with a lot of chest congestion. After using the Robitussin again and coughing up a fair bit of phlegm I felt that most of my symptoms had distinctly improved. For the first time since testing positive I was feeling better. However my breathing was somewhat labored, like a mild wheezing without any sound. And I had shortness of breath after walking up the stairs. 

I knew that people with Covid could have a sudden drop of oxygen which was a sign that you might need to go into the hospital for medical assistance such as oxygen. I got out my pulse oximeter and clamped it on my finger. It quickly climbed up to 95% oxygen. No worries there.

Should You Use a Pulse Ox When You Have COVID-19?

Then I got concerned that the Covid virus may have now reached deeper into my lungs and that it was affecting my breathing. I was really in a classic race condition. This chart shows the race between the Virus and the Antivirus. In this model the Antivirus is the combination of Covid antibodies (which are very low in my case) and the antiviral drug remdesivir given on Days 3, 4 and 5. The Virus was replicating and the Antivirus was attacking it and reducing its ability to grow. This was my last day of remdesivir. Would the drug continue to work after today? If not, the Virus could win the race. This picture did not look promising.

(The numbers on the left axis are not real world measurements of Virus or Antivirus levels, they are abstract numbers used in the spreadsheet to show this chart.)

On the other hand, vaccinated people with healthy immune systems might do just fine in this scenario. Their immune systems responded to vaccinations and prior Covid infections and generated a higher level of Covid antibodies that circulates in their blood when Covid is first contracted. The combination of higher Covid antibodies with the antiviral drug on Days 3, 4 and 5 is enough to kill off the virus.

So a critical question was “How long would remdesivir remain in my body and continue to have antiviral benefits?”

I did some Google searches and could not find a clear answer to this. However there were some articles that said the half-life of remdesivir was about an hour. That was worrisome; it didn’t seem like that would be long enough to win the race against the virus.

To get a better answer I did what I have been doing for the last few months when I did not get a good answer from Google search for more complicated questions. I posed the questions to ChatGPT. It gave a very good explanation and reassured me that remdesivir would probably work long enough for me to recover.
____________________________________________

Question: How long is remdesivir active in combating Covid after infusion?

Answer: Remdesivir undergoes a process called intracellular metabolism, where it is converted into its active form which works by inhibiting the replication of certain viruses, including the SARS-CoV-2 virus responsible for COVID-19. It is incorporated into the viral RNA chain during replication, leading to premature termination of viral RNA synthesis.

The half-life of remdesivir is relatively short, averaging around one hour in plasma. However, the drug’s effect on combating COVID-19 extends beyond its half-life. Remdesivir’s antiviral activity is primarily driven by its active metabolite, which has a longer half-life and remains in the body for a more extended period.

The exact duration of remdesivir’s activity in combating COVID-19 after infusion is not precisely defined. However, clinical studies have shown that the drug’s beneficial effects can persist beyond the treatment period. It is believed that the active metabolite continues to exert its antiviral effects on viral replication even after the infusion is completed.
____________________________________________

In the afternoon my nurses arrived for the final infusion. They were now experts at it. In no time the head nurse had mixed the remdesivir and set it up on my IV pole. It was again scheduled for a 1 hour drip. The nurse said they had quite a number of calls that day, about 19, and she wondered if I would be able to remove the IV line by myself at the end. I had done this in the past so I said OK so that they didn’t have to wait around for an hour. I bid them goodbye as they went off on their next mission to provide home service for people in need. I thanked them profusely and told them what a great service it was. 

When the drip stopped I took the bag and tubing off the IV stand and brought it over to the sink in the bathroom. I got N to press a piece of gauze over the insertion point while I removed the holding tape and pulled out the line. There was a big squirt of blood into the sink. I got a large fresh piece of gauze and put it in a better location, applying enough pressure to stop the bleeding. My arm was pretty bruised around the vein after having been in place for three days and used for three infusions. But that was a pretty minor inconvenience, all things considered.

Later on I gathered together all the leftover medical supplies that had been delivered. Even after allowing for spares for each item, there was a huge amount of extra, most of which hadn’t even been needed. This all had to be thrown into the garbage. Even though most were in protective sterile packaging, a clinic or the pharmaceutical company wouldn’t take it back, especially since they had been in a house infected with Covid. The pharmacy had an exact order of what I needed for two infusions. Why they packed so much extra into the box is beyond me. This was just another example of terrible waste in our medical system. Here’s a picture of all the extra medical equipment that had to be dumped into the garbage.

The following day I had a follow-up phone meeting with the nurse practitioner at the Covid Clinic. I reported that most of my original symptoms had improved and she seemed to think that I was doing pretty well. I told her my concern about the new difficulty breathing. She said that it was likely due to the inflammation that had been caused by Covid infection in the lungs. I asked if ibuprofen, which I’ve always found to be the best medicine to combat inflammation, would help but she said she didn’t think so and that I would just recover with time. Overall she did not seem to be too worried about my case and just scheduled another follow-up call for the end of the week.

As the week progressed, I seemed to be getting better each day. I still had some chest congestion accumulation overnight but it usually cleared without resorting to Robitussin. My breathing wasn’t fully back to normal but I knew from a past bout of pneumonia that lung infections are a slow recovery process that can take a month or two. 

However I didn’t know if I was out of the woods. Many people who had Covid have reported “Long Covid”, symptoms that persist for three months and more. 

Statistics Canada reported that nearly 15% of people who contracted Covid after Dec 2021 experienced lingering symptoms such as fatigue, shortness of breath or brain fog three months or more after their initial infection. This was a marked improvement from earlier in the pandemic when 25% of people who had Covid reported symptoms three months after their infection. It seems that the likelihood of Long Covid increases with the severity of the initial infection. Only 6% of those who rated their initial case as mild came down with Long Covid.
What studies reveal about long COVID

Not a lot is known about what causes Long Covid or how to treat it. Research is being done but there do not seem to be very many conclusive results that lead to reliable treatment as of yet.

On my phone call at the end of the week with the nurse in the Covid Clinic, I asked about my risk for Long Covid. She said that I didn’t fit the profile. I was showing distinct improvement while people with Long Covid don’t get better at all. I was still concerned about relapse since my Covid antibodies are so low. She said I wouldn’t likely get reinfected by the same Covid virus that was still circulating in our house as we were recovering. There was a risk of reinfection from a different Covid variant but that would have to come from the outside. 

The guidelines for self isolation for immunocompromised people were to stay at home for 10 days and until your symptoms were improving for at least 24 hours. I now met these conditions. It was the weekend and finally some nice, sunny weather after a rather long winter and dreary spring. Open Doors Toronto was on and we went out to see a few buildings of interest: the Ismaili Center which is adjacent to the Aga Khan Museum and the Canadian Film Institute which is the old estate of E. P. Taylor. It was nice to get out like a normal person.