20200426u Day 117: I can see the beach waves at the end of the wormhole

Davenport Beach, CA. April 26, 2020
Davenport Beach, CA. April 26, 2020
Bonny Doon Beach, CA. April 26, 2020

Santa Cruz, CA: Today, I wanted to make it into the water, so I drove to Bonny Doon Beach. The parking lot there was full. It was one of the few open roadside parking lots I saw. The rest of the parking lots were closed and people were parking along the side of the road. At the beaches, it almost felt like pre-pandemic. While there were a few people wearing face masks, most did not. People did try to maintain six foot distance between one another for the most part. There didn’t seem to be any concern when passing each other on the trails.

I hear from my Mom that masks are going to be mandatory in her county in Texas tomorrow – two days after masks were required here.

20200425S Day 116: Everyone Must Wear a Face Mask

Farmers Markets in Santa Cruz, CA on April 25, 2020 – First day of Santa Cruz County order requiring the wearing of face masks while in public

Today, everyone was wearing masks at the Farmers Markets. There were one way lines with people separated by six feet. Later, in the afternoon, I rode up highway 1 and the cars were also social distancing at six feet between automobiles – it was packed! Since the park parking lots were closed, everyone was parking on the side of the road. It felt like the 4th of July. You could tell that everyone is done with sheltering in place and ready to return to normal activities, especially when they can head to a sunny beach. Everything is still feeling to me that I will be out of this pandemic wormhole by June 8th. I’m still curious how life will be different in the new universe I’m surfing to.

20200422W Day 113: No Unnecessary Physical Contact on Aptos Street

20200422_AptosStBBQ

Aptos, CA: Social distancing guidelines at Aptos Street BBQ include guidelines that:

EMPLOYEES and CUSTOMERS SHOULD: Not shake hands or engage in any unnecessary physical contact

As I surf back to a universe in which I can eat BBQ inside a restaurant, like Black’s BBQ in Austin, Texas, I thought I’d check to see how things were at Aptos Street BBQ. You can no longer drink a beer inside and the selection of beers on tap is reduced. You can buy bottles and cans of beer and purchase BBQ-to-go.

Face coverings are now required in order to enter the restaurant. And no more horsin’ around with “unnecessary physical contact”.

In RV news, the water on the floor of my RV appears to be coming from the AC unit.

20200422_RV_AC_leak

 

20200419u Day 110: Almost 2.5M confirmed COVID-19 Cases Worldwide

Two days ago in 20200417F Day 108: Surfing the Multiverse back through a Pandemic Wormhole, I noted:

It is looking now that the 10x/month rate is still on track from March 19 and the confirmed COVID-19 cases are expected to hit 2.5M by April 19.

and data from https://www.worldometers.info/coronavirus/ shows 2,406,575 worldwide confirmed cases of COVID-19. I’m happy to see that the number of total cases is leveling off. One warning sign is the growing number of cases in Russia. If COVID-19 outbreaks are not contained quickly in Russia, then there could be 10x the number of cases in Russia by May 19th. As I continue surfing to a universe where SARS-CoV-2 returns to the wild, then something needs to change in Russia because the number of cases and deaths are currently increasing rapidly.

Screen Shot 2020-04-20 at 9.51.50 AM
Data for April 19, 2020, from https://www.worldometers.info/coronavirus/

In local news, I went on a bike ride with my brother. There were quite a few other bikers and life is beginning to return to normal in Santa Cruz. The beaches and walk along the beach were also full. Santa Cruz County has 104 cases and 2 deaths confirmed for COVID-19 out of a population of 300,000. It will be interesting to see what the serological testing shows in the county. New York plans to begin serological testing on Monday.

 

20200418S Day 109: Review of Recent COVID-19 Related Research

Santa Cruz, CA: Today has been a slow day, like all days under shelter-in-place seem to be. I walked to the farmer’s market and the grocery store. Both places had a much larger number of people wearing masks – about 60%. Social distancing was enforced through one-way aisles and tape markers on the ground.

It is still very difficult for me to be productive. Twitter is my main time suck at the moment. There is so much posting of what appears to me as misinformation. I think it’s time to educate myself and at least see what people are saying who have taken the time to write up and submit research papers.

The first paper I’d like to review is Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates. The authors of this paper are trying to determine the structural similarity of ACE2, specifically the part of ACE2 involved in binding to SARS-CoV-2, across mammals and vertebrates. The first thing I notice is that the authors are from a diverse group of worldwide top-notch universities and organizations. Some points of interest to me are:

  1. There are 25 amino acids at the ACE2 binding site which are important for binding to SARA-CoV-2.
  2. Molecular phylogenetics shows that at least one human coronavirus (HCov-OC43) may have originated in cattle or swine. HCov-OC43 is a beta coronavirus that is now believed to have been the cause of an influenza pandemic in 1889-90.
  3. 18 out of 19 catarrhine primates analyzed scored “very high” and also had 25/25 identical binding residues for binding; and the 19th, the Angola colobus, scored “high” with at least 20/25 identical binding residues.
  4. 3/3 species of Cervid deer and 12/14 cetacean species also scored “high”.
  5. Camels and pigs both scored “low”.
  6. 9/9 species of Felids scored “medium” – there have been reports that a domestic cat became infected with SARS-CoV-2.
  7. 3/3 species of pangolins scored “low” or “very low” for ACE2 binding.
  8. The ACE2 RBD residues critical for effective binding to SARS-CoV-2 S protein are S19, Q24, T27, F28, D30, K31, H34, E35, E37, D38, Y41, Q42, L45, L79, M82, Y83, N330, K353, G354, D355, R357, and R393. The ACE2 RBD glycosylation sites N53, N90 and N322 were also included.
  9. “Very High” scores have at least 23/25 matching residues, and 7/7 of the residues K353, K31, E35, M82, N53, N90 and N322, and do not have N79, and the up to 2 non-matching residues have conservative substitutions.
  10. “High” scores have at least 20/25 matching residues, have K353, have only conservative substitutions at K31 and E35, do not have N79, and up to one non-conservative substitutions among the up to 5 non-identical residues.
  11. “Medium” scores have at least 20/25 matching residues, only conservative substitutions at K353, K31, and E35, and up to two non-conservative substitutions in the 5 non-identical residues.

The second paper I noticed was Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions. The title says it all – the researches found that SARS-CoV-2 “generally maintains infectivity when airborne over short distances, in contrast to either comparator betacoronavirus”.

A third paper, Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19, found increased expression of lung ACE2 in obese mice.

A fourth paper, Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling, found that “SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility.”

In a fifth paper, COVID-19 pandemic: A Hill type mathematical model predicts the US death number and the reopening date, the author predicts that “by the mid June or early July 2020, the outbreak will strongly decay and the US will have about 800K confirmed cases and less than 50K deaths.”

In a sixth paper, Delayed clearance of SARS-CoV-2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs, the authors find that males have delayed viral clearance after infection (by 2 days) and that the testes was one of the highest tissue sites of ACE2 expression.

And finally, a seventh paper which seems like a good one to stop with for now: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes. This one has a lay summary which sounds significantly enough to me on first reading to quote in entirety here:

Lay summary: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it’s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven’t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don’t yet know what the real-life significance of this variation is, but it’s possible that these variants decrease the protein’s ability to interact with the SARS-CoV-2 virus, thus decreasing the person’s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.

Some key points mentioned in this paper:

  1. ACE2 is on the X chromosome and because males have only one X chromosome, males carry only one copy of the ACE2 gene.
  2. 332 coding variants were found that affected the ACE2 coding sequence. 16 of these were loss of function mutations. 11 coding variants changed specific amino acids that interact with SARS-CoV-2. 29 coding variants were nearby, within two amino acids.
  3. Two of the most found alleles are chrX:15600835:T:C / p.K26R (allele frequency 0.5%), chrX:15600857:A:G / p.S19P (very rare except in African ancestry with allele freq of 0.1-0.2%)
  4. A few more residues of interest that I saw were G352V, D355N, A396T, N397D, F400L, T27A, E35K, E37K, L39P, F40L, S43N, A80G, M82I, P84A, and L27F (male only).