Peking Union Medical College: New Treatment Rescues Severe COVID-19 Patients

Image credit: “Crystals of IgG antibodies 02” by Josef Reischig is licensed under a CC BY SA 3.0

The paper that we’ll be demystifying can be found here, if you want to follow along.

One of the comforts we can take during this crisis is that severe cases of COVID-19 are uncommon in young, healthy people. Now, this can’t be said for the immunocompromised, the elderly, those with asthma, etc., so stay home! For those who have become critically ill with COVID-19, proper treatment is everything. With the threat of organ failure and severe pneumonia, it’s key that we understand how to best treat these patients.

In severe cases, researchers noticed a drop in peripheral lymphocytes, immune cells that patrol the bloodstream and attack viruses. Coupled with high inflammation, the swollen redness that occurs after an injury, this means an overwhelming immune reaction. Previous research discovered that this was the primary source of organ failure in SARS, a similar virus. As such, intervening during this immune response in COVID-19 cases is critical.

A team in Jin Yin-tan Hospital did just that when their COVID-19 patients reached a critical state. They administered high-dose intravenous immunoglobulin (IVIg), a treatment often reserved for immunodeficiency or autoimmune disorders.

Immunoglobulin, as known as antibodies, are Y-shaped molecules made by the immune system to neutralize intruders, such as COVID-19. IVIg injects large amounts of antibodies into the bloodstream. The exact reason that introducing a big part of the immune response to quiet down the immune response works is still unknown, but it does, so doctors use it. A common theory is that it increases the amount of FcgRIIB in the body, a protein that shortens the lifespan of antibodies in the bloodstream. This means that while the number of antibodies rise temporarily, they expire faster in the long term.

An antibody. They really do look like a Y. (Complementarity-determining region. Published 2020. Accessed March 24, 2020.)

The doctors in Jin Yin-tan hospital debuted their brave new use of the treatment on three COVID-19 patients. These are their stories.

Patient 1

Patient 1, a normally healthy 56-year-old man, was admitted on January 22, 2020. He had sore throat for the last four days, and a fever for the last two. Patient 1 had already been to local clinic, where he was given oseltamivir, a flu drug, and azithromycin. Neither of these caused any improvement.

When he arrived at the Emergency Department, Patient 1 was diagnosed as SARS-CoV-2 positive, and his CT scan showed dense patches inside and thickening around the right side of his lung. By the time he was admitted, he had no fever and normal vitals. His liver and kidneys were working fine. When listening to Patient 1’s lungs, doctors found them clear. All in all, nothing to note.

Patient 1’s lab results showed an abnormally low lymphocyte count and high levels of markers for inflammation. He was given moxifloxacin, another antibiotic, and was kept under close watch.

It was January 26 when Patient 1’s vitals started to become unstable.

He began to develop a cough and shortness of breath, his blood oxygen falling, and his inflammatory markers rising further. A new CT scan showed the infection had spread to both of his lungs. Patient 1’s diagnosis was changed to “COVID-19, severe type.”

On the seventh day of his stay at Jin Yin-tan, January 28, the doctors started with high-dose IVIg. His regimen was 25 grams daily for the next five days, along with his moxifloxacin.  The day IVIg was added, Patient 1’s fever disappeared, with no side effects being reported.

In the coming days, Patient 1’s vitalscontinued to improve. He was liberated of his oxygen support as his blood oxygen returned to normal, as did both his lymphocyte count and inflammatory markers. His final CT scan showed diminishment of the inflammatory lesions, and his new swab tests on February 2 and 3 were negative for SARS-CoV-2.   

Patient 1 was discharged after 15 days, on February 5.

Patient 2

At 34 years of age, Patient 2 had a history of high blood pressure spanning back two years. He had managed it well with a regimen of valsartan and felodipine, two drugs at lower blood pressure.

Patient 2 had been dealing with a fever and dry cough for the last ten days, but it was a shortness of breath from the previous day that pushed him to seek out the local hospital on January 28, 2020. Testing positive for SARS-CoV-2, he was sent to Jin Yin-tan the next day.

Patient 2’s physical evaluation was poor, finding an elevated temperature and blood pressure, and low blood oxygen. His blood test revealed a slight increase in inflammation markers, as well as a low platelet count, which would prevent his blood from clotting properly. It also showed increased

creatine kinase and myoglobin, two markers for muscle damage. On January 30, a CT scan showed opaque lesions in both of Patient 2’s lungs, especially his right. He was instantly diagnosed with COVID-19, severe type.

The doctors immediately started his 5-day course of IVIg, again at 25 grams per day. Patient 2’s fever receded on the treatment’s second day, along with a steady improvement in his ability to breathe. His new scan on February 3 showed the disappearance of many lesions, and a second swab test turned up negative for SARS-CoV-2.

Patient 2 was discharged after 8 days, on February 5.

Patient 3

Patient 3, a generally healthy 35-year-old woman, was in close contact with her SARS-CoV-2 positive colleague a couple of days before she started showing symptoms. Beginning in January 19, 2020, Patient 3 had a general malaise and low fever, accompanied by mild coughing. After a CT scan and swab test marked her as SARS-CoV-2 positive on January 20, she was kept under close observation. Patient 3 was given lopinavir/ritonavir, a one-two punch of antiviral drugs, but the infection persisted. On January 22, her fever reached 39°C. She was admitted to Jin Yin-tan Hospital two days later.

On admission, her fever had receded, and outside of a blood pressure just below normal range, her vitals were normal. Patient 3 also had a low lymphocyte count and high level of inflammatory markers, but less so than Patient 1. However, while her lungs sounded clear, a new CT scan on January 24 showed a progression of the infection into both of her lungs.

Patient 3 took a turn on January 29, when she complained of a shortness of breath, her blood oxygen dropping. New CT scans displayed significant deterioration in the lungs. Her lymphocytes continued to fall, and inflammatory markers rose even further. Patient 3’s diagnosis of COVID-19 went from moderative to severe.

Like the other patients, Patient 3 was started on a 5-day course of IVIg at 25 grams daily. However, she was also given 40 mg of daily methylprednisolone, a drug to decrease her inflammation. This enhanced treatment caused her fever to disappear that day, and her blood oxygen to be restored on the next.

Patient 3 tested negative for SARS-CoV-2 on both February 2 and 3, and a final chest CT scan showed her cleared.

Patient 3 was discharged after 21 days, on February 9.

The team at Jin Yin-tan definitely showed IVIg as a promising potential therapy for severe COVID-19 patients. That being said, we have to remember this was performed on three patients. While no side effects were seen in these three, other potential patents may react poorly. As scientists, it’s important to gather more data to confirm a conclusion. The team suggests a randomized clinical trial, in which patients receive the IVIg based on whichever group they’ve been randomly assigned to.

Still, this is a strong candidate from rescuing our worst cases of COVID-19. That’s quite the step!

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