Tag: covid

Those RNA Viruses

Note: this a really basic discussion of a very complex and ever-evolving topic.

From Duffy S (2018) Why are RNA virus mutation rates so damn high? PLoS Biol 16(8): e3000003. https://doi.org/10.1371/journal.pbio.300000

he genetic information that codes for traits in all living organisms are found in DNA or RNA or a combination of the two. Even viruses, not really seen as living organisms, have genetic material. They either code them in RNA (RNA viruses) eg. Influenza or DNA (DNA viruses) eg. Herpes.

Where DNA viruses are quite big, RNA ones are much smaller. Also, RNA viruses replicate (multiply) way more than DNA viruses.

(Just a reminder, DNA and RNA are made up of bases called nucleotides).

To exert their disease-making effects all viruses have to enter the cells of the organism they are attacking. So they find a receptor that fits them on the membrane of the cell, fuse with that receptor and then worm their way into the cell.

Once in the cell, a DNA virus finds its way into the nucleus of the cell and fuses with the host organism’s DNA. As it divides and multiples, it uses the organism’s enzymes it needs for multiplication — the polymerases. Ensconced in the nucleus, DNA viruses tend to be more stable over time. They multiply and mutate less and therefore may be easier to treat.

The RNA virus on the other hand, stays in the cytoplasm and divides in there, using its own polymerases. Being smaller, using its own polymerase and away from the influence of the host organism, the RNA divides very fast and often. This leads to the RNA virus being able to switch out the nucleotides in its RNA often resulting in a different strain than what entered the organism — a process we commonly term “Mutation”!

It has been calculated that RNA viruses mutate on an average of once every 50,000 base pairs per infection. DNA viruses do that once every 50,000,000 base pairs per infection.

Now DNA viruses have mutations too but one, they are not as frequent and besides, the organisms polymerases can cut out these renegade nucleotides. The RNA’s polymerases lack this repair ability.

Mutations in RNA viruses are often set off when the environment in the cell changes — like when it senses the presence of a new vaccine or antibodies or medications. This ability to multiply fast and often is the reason why we never seem to get a good enough vaccine for the flu. That is why we sometimes need to treat viral infections like HIV and Hepatitis C with more that one medication.

This ability to mutate often also leads to instability of the RNA virus — it can generate a lot of mutants which do not survive or which may even be more virulent. Much more virulent than the organism that entered the cell.

Now in most normal humans, the body is able to mount a level of immunologic reaction to the vast number of viruses that affect humans. However, if the virus is totally new to humans, that ability is not available for months to even a year. Thus when a novel RNA virus spills over from another mammal into a human, those initial months to a year are very unpredictable. We are dealing with a virus that can mutate into a more virulent strain and against which the body still has no defense.

COVID-19 is an RNA virus that spilled over recently!

 

The Whistleblowers

I have wondered how Li Wenliang, an ophthalmologist, became the face of the group of doctors in Wuhan I call “The Whistleblowers”. These were the doctors whose warnings about the outbreak of a contagious and novel pneumonia-causing virus in Wuhan, China went unheeded by those in authority.

So I decided to do some digging. Reporting in the WSJ, NYT, and other online publications have been very helpful in this effort.

By the second week of December 2019, doctors around Wuhan were seeing patients with symptoms that included fever, coughing, fatigue, and aching limbs. Initially, some doctors thought it was bronchitis but soon most realized the condition was atypical pneumonia. They tried to treat these cases unsuccessfully with antibiotics.

Even though a lot of the patients came from the Huanan Wet Market, the connection was not made until later.

On December 16, an ER doctor named Ai Fen admitted a 65-year-old man to the emergency room at Wuhan Central Hospital whose only symptom was fever. A chest CT showed bilateral lung infections he was given antibiotics and antipyretics. The fever did not break so he was transferred to a tertiary center for advanced care. It was only after the transfer that Dr. Ai learned that the man worked at the wet market.

On December 27, Dr. Ai admitted another patient with similar symptoms. She ordered a chest CT and lab work. By the next day, she had seen 6 more such cases. Four of them worked or were in some way affiliated with the Huanan wet market.

She started to wonder if she was seeing a contagious disease. She notified the hospital leadership, who in turn notified the district CDC office. That office had been getting similar reports from other hospitals and clinics in Wuhan.

On December 30, she got the lab results back from the patient she had seen 3 days earlier. It read “SARS Coronavirus”.

A terrified Dr. Ai notified the hospital leadership of her findings. She also shared a photo of the lab result and a video of a chest CT scan showing pneumonia caused by this new virus with a medical school classmate.

Somehow, this photo and video clip ended up on the phone of an ophthalmologist who also worked at Wuhan Central. His name was Li Wenliang.

That afternoon, he shared it with his group of med-school classmates on WeChat with over 100 members.. (Bear in mind that in China, all social media sites are spied on by the government.) He posted:

“7 SARS cases confirmed at Huanan Seafood Market…Patients quarantined in the Emergency Department of our hospital.”

Another member warned that he could be censored for sharing such information.

He replied:

“Coronavirus confirmed, and type being determined…Don’t leak it. Tell your family and relatives to take care.”

Well, who can avoid sharing such juicy information in this age of social media? By that night, the information was all over WeChat.

The censors showed up shortly thereafter.

The next day he was reprimanded at work. On January 3, he got a visit from the police who warned him and censured him for “making false statements on the internet”. He was made to sign a letter of admonition promising not to do it again.

Reportedly, eight Wuhan doctors in all were admonished by the police for discussing the outbreak on social media in the first week of January 2020.

One of these doctors was Dr. Xie Linka, an oncologist at Wuhan Union Hospital. She learned from her Pulmonology colleagues that the hospital’s respiratory unit was housing many patients with an unknown type of pneumonia. She also later posted on WeChat warning members in her chat groups to wear masks and ventilate areas.

Dr. Liu Wen, a neurologist at Wuhan Red Cross Society Hospital was another doctor who was admonished. He also found out about cases in his hospital and posted about or discussed it on WeChat.

By December 30, doctors who were seeing and treating these patients with the strange new pneumonia knew what the authorities in Wuhan would not accept — that it was contagious and had human-to-human transmit-ability.

On December 31, the Wuhan branch of the National Health Commission issued a statement that confirmed the outbreak of a disease that had so far infected 27 people. It further said:

“The investigation so far has not found any obvious human-to-human transmission or infection of medical staff. The disease is preventable and controllable.”

On January 1st, 2020, Dr. Ai admitted a patient with symptoms of the strange new pneumonia. He ran a clinic near the Huanan market and had been treating a lot of those patients in the preceding weeks. Now he was sick. She alerted the hospital leadership and stressed that she believed the disease was contagious. She asked her staff to put on masks when treating those patients. For that, the hospital leadership admonished her the next day for spreading rumors and destabilizing Wuhan.

Unbeknownst to Dr. Ai, one Dr. Lu Xiaohing, Director of Gastroenterology at the Wuhan Municipal Hospital had received news a week earlier on December 25 2019 of the medical staff at two hospitals in Wuhan who had fallen sick while taking care of patients suffering from new and strange pneumonia. Dr. Lu did share the news but it is unclear if he was also admonished.

These admonishments may have shut up the whistleblowers but not the spread of the virus. With cases mounting not only in Wuhan but in other cities and international concerns increasing, a team led by the SARS expert and renowned epidemiologist, Dr. Zhong Nanshan, was sent to Wuhan. On January 20, 2020, Dr. Zhong would announce what the doctors in Wuhan had known all along — that the virus could be transmitted from human-to-human. At that point, there were 198 cases reported and three deaths.

Sadly, the very group of people who tried to warn the authorities all long that the virus had the ability to be transmitted human-to-human would suffer from this virus because they were not heeded. One of them was one of the whistleblowers — Dr. Li Wenliang.

On January 7, Dr. Li saw a patient with angle-closure glaucoma at Wuhan Central. Unbeknownst to him, the patient was a storekeeper at the Huanan wet market who had the virus. By January 10 he had developed a fever and a cough. On January 12, he had to be admitted because of extreme dyspnea. Dr. Li did not do well. About a month after he contracted the virus from a patient, he succumbed to pneumonia, dying on February 7 at the age of 34. He left behind a pregnant wife and a son.

As of March 4, 2020, China’s National Health Commission reported that more than 3,300 healthcare workers nationwide had been infected and at least 13 have died. Overall, 105, 938 patients have contracted the virus so far worldwide. 3567 people have died and 58,625 have recovered. Whereas the severity in China seems to be waning, the outbreak is on the increase in Iran, South Korea, and, Italy. Also, though the mortality rate looks low, it is very contagious and seems to be still spreading quickly. If millions get infected, even a low mortality rate will still result in lots of deaths.

The outbreak is also having a rather terrible impact on the world’s economies and may lead to a worldwide recession.

This makes me wonder what could have been if only those authorities in Wuhan had listened…listened to those doctors…those whistleblowers.

May Dr. Li Wenliang rest in peace. May all the doctors and nurses all over the world who are caring for patients afflicted by COVID-19 and other infectious diseases be safe.