Signs of Fall 5: Continuing Saga of SARS-CoV2!

SARS-CoV2. Figure by CDC, Public Domain

(Click on the following link to listen to an audio version of this blog ….SARS-CoV2!

I was trying to come up with a metaphor that describes humanity’s relationship with the on-going evolution of the SARS-CoV2 virus (i.e. the virus that causes COVID-19). My first idea was to put all of us in the grandstands at some world-sized stadium where we could all sit (and, maybe, have a hot dog and a beer) and watch the evolution of SARS-CoV2 play out down on the field. But, then I thought, no, we are not in some comfy, stadium seats watching this virus play on down on a distant field. Instead, we are on the field with the virus, or, maybe, even more accurately, we ARE the field within which the virus is traveling and changing. Sorry, no hot dogs or beer for us! No simple metaphor for us, either.

A year ago, I wrote a series of three very detailed blogs about the SARS-CoV2 virus. Please check those out of you are interested in specifics concerning mutations and data that each variant generated during the pandemic (see Signs of Fall 7 (October13, 2022), Signs of Fall 8 (October 20, 2022) and Signs of Fall 9 (October 27, 2022)).

Corono viruses. Photo by CDC.Public Domain

The first form of SARS-CoV2 (the “wild type” virus) originated in China in the late months of 2019. Over a 15 month period this initial variant of SARS-CoV2 caused over 100 million cases of COVID-19 around the world, and caused the deaths of 2.7 million people! The spread of this virus triggered the world-wide pandemic and disrupted the lives and of billions of people.

The first official case of a SARS-CoV-2 infection was reported in Wuhan, China, on 31st December 2019. This first officially described patient had an atypical pneumonia. It is thought that the SARS-CoV2 virus emerged some weeks before from live animals (like bats, civet cats, racoon dogs or red foxes) being sold at a “wet market” (the Hunan Seafood Wholesale Market) in Wuhan, China. The virus then slowly and steadily infected and spread through a growing number of people first in the immediate area of the market and then in more distant locations due to person to person transmissions. Many initial SARS-CoV2  cases, undoubtedly, went undetected. An alternative origin hypothesis for SARS-CoV2 has it escaping from the nearby Wuhan Institute of Virology although most virologists and investigative agencies think that this is a very unlikely possibility.

SARS-CoV2. Figure by A, Solodovnibov and V. Arkhipova. Wikimedia Commons

SARS-CoV2 is closely related to SARS-CoV (the virus that caused the SARS outbreak in 2003). This new form of the SARS virus, though, had adaptations that made it more contagious than the original SARS-CoV and also better at avoiding the immune system’s detection.  Alterations in the amino acid sequences of the S-1 protein subunits of the Spike Proteins of the virus may have contributed to both of these features of SARS-CoV2. Also, a mutation in the virus that allowed human cellular enzymes to trigger S-1 and S-2 cleavage in the Spike Protein (a step which forms the enzyme that catalyzes the attachment of the S-1 to the potential host cell’s surface protein receptor (typically an ACE2 protein)) may have made this new form of the SARS virus increasingly virulent and infectious.

Viruses do not stay the same. Every time a nucleic acid replicates (whether it is the DNA in your cells or the RNA in the SARS-CoV2 virus) it changes. Mistakes are made in the replication and the nucleic acid can then take on new properties and potentials.

In the case of SARS-CoV2 most of the new RNA expressions were non-functional and those changed viruses disappeared. A few of these new RNA forms, though, began to make proteins that made the virus into a more effective infectious agent, and these new variants, then, superseded the older forms. The expected evolutionary trajectory of viral evolution is an increase in the transmutability of the virus but a decrease its disease intensity and mortality. Hosts can survive to, hopefully, from the virus’s point of view, make even more viruses. This scenario satisfies the “selfish gene” hypothesis and should result in more and more copies of SARS-CoV2’s nucleic acids!

SARS-CoV2 viruses emerging from a human cell. Photo by NIAD, Wikimedia Commons

This expected evolutionary scenario seems to have unfolded. The initial, “wild-type” SARS-CoV2 had a mortality rate of 2.4%. The second wave (“Alpha” (B.1.1.7)) was more contagious due to mutations in its protein by which it attached to host cell receptors, but had a mortality rate of 1.9%. The third wave of SARS-CoV2 (“Delta” (B.1.167.2)) had mutations that helped it to attach to host cells more readily and also replicate more rapidly in those host cells. Delta caused very serious disease but still had a reduced mortality rate of 1.6%.

The fourth wave of SARS-CoV2 evolution generate the variant called Omicron. Mutations that allowed the virus to evade immune detection, to attach to a host cell’s receptor site more securely, and speed up its replication inside a host cell generated a virus that was extremely contagious. Omicron spread more rapidly than any of the previous variants, but had a much lower mortality rate (0.4%) possibly because of its ongoing evolutionary path but also because of increased population resistance due to vaccinations and previous infections.

Variants of Omicron continue to be the major forms of circulating SARS-CoV2. The initial Omicron was superseded by BA.5 Omicron which circulated from May 2022 to January 2023. BA.5 Omicron was then superseded by XBB.1.5 Omicron (“Kraken”) which was the dominate circulating SARS-CoV2 variant from January 2023 until August 2023. The Kraken has just been replaced as the dominant Omicron variant by Eris EG.5 (in mid-August, 2023 20.6% of all COVID cases in the United State were caused by Eris EG.5).

SARS-CoV2 in human lung. Photo by NAID-NIH, Wikimedia Commons

In February 2023 there were 600 lineages of Omicron in circulation. Most of these variants did not cause serious disease, but there is always the possibility that some new re-shuffling of genes and proteins will result in a new pandemic agent.

The changes in these virus variants basically involve ways to make the virus replicate more rapidly, attach to the cellular receptors more vigorously, and find ways to evade existing agents of immunity. The general trend, though, in the evolution of these viral forms are the expected increases in contagiousness and decreases in disease severity and mortality.

There is a new variant of Omicron that has just been detected from a small number of patients in Denmark, South Africa, the United States, the United Kingdom and Israel. This new variant is called “Pirola” (BA.2.86). Pirola is of concern because of the sheer number of mutations it possesses. It has 30 different mutations in its spike proteins alone. Scientists are not certain if this new viral variant represents a novel, major threat to human health. They do not know if it will cause more severe disease or be able to bypass the existing immune systems that have been so painstakingly established in our population. They don’t know if this new mixture of characteristics and features is deadly or if it will simply fade away like most of the random mutational combinations have similarly disappeared. New experiments by Moderna and several other labs, though, that were just released, indicate that antibodies from this fall’s booster shot and also from previous vaccines or SARS-CoV2 exposures should be able help to control Pirola.

Sneeze and aerosol particles. CDC, J. Gathany. Wikimedia Commons

This Fall there will be more COVID cases (along with flu, RSV and a slew other viruses). We can each protect ourselves and each other by employing some common sense strategies: get the latest COVID booster (and a flu shot, and, maybe, the new RSV vaccine)! Mask when you go into highly populated spaces (like airports or crowded stores!). Ventilate your space! Recognize the COVID symptoms (sore throat, congestion, fatigue, fever, cough). Have home test kits on-hand! Avoid passing the viruses on (self-quarantine!).

Be smart! Stay healthy!

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