COVID-19

Check out Dr. Wright’s new vlog: Close Reading COVID-19!

Close Reading COVID-19 is hosted by Dr. Wright and his daughter Emily, who has served as Dr. Wright’s research assistant since 2011. In this program, we take a deep dive into the research on SARS-CoV-2 using the same close reading strategies that Emily, a high school English teacher, uses with her students.

In the very first episode of Close Reading COVID-19, we take a look at the research on SARS-CoV-2 Variant of Concern B.1.1.7, which was first detected in the United Kingdom in fall of 2020 and has now been detected in 45 states in the US. We also examine hospitalization data to see how B.1.1.7 might be affecting youth in the UK and explore the data on PIMS/MIS-C, the inflammatory syndrome that some children and young adults develop after a COVID-19 infection. Finally, Dr. Wright offers his advice on masking, indoor gatherings, and vaccinations.

For links to the articles mentioned in the program, check out the slide show.

COVID-19

SARS-CoV-2 (COVID-19) Update

It’s time for our next 14-day moving average determinations and projections for infections and deaths from SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the WORLDOMETERS aggregators data set to make our projections of future total infections and deaths since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

In the United States, SARS-CoV-2 deaths have decreased for the second time in a 14-day period. There were 843 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 39,769 infections per day. This decrease in infections over the last three 14-day periods may represent increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 38 of plan). On 2/26/21, 81,942 new infections occurred in the United States. There were also 2,280 deaths. The number of hospitalized patients is decreasing, and only 15,478 patients are critically ill. The number of critically ill patients has decreased by 4,449 in the last 14 days, while 28,426 new deaths occurred. This suggests that the number of critically ill patients is decreasing because a large number of patients are dying. 

As of 2/16/21, we have had 523,116 deaths and 29,138,228 SARS-CoV-2 infections in the United States. We have had 990,465 new infections in the last 14 days. We are adding 495,232 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 2/26/21, nineteen states have had greater than 500,000 total infections, and 29 states had greater than 5,000 total deaths. 

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. In North Dakota 9.18% of the population was infected (ranked #1), and in South Dakota 8.03% of the population was infected (ranked #2).

As of 2/26/21, in the United States 8.76% of the population has had a documented SARS-CoV-2 infection. In the last 3 months 5% of our country became infected with SARS-CoV-2. 

As of 2/26/21, California was ranked 26th in infection percentage at 8.74%. In North Dakota 13.08% of the population was infected (ranked #1) and in South Dakota 12.67% of the population was infected (ranked #2). Twenty-five states have greater than 9% of their population infected and 44 states have greater than 6% infected. Only four states have less than 4% of their population infected: Oregon (3.67%), Maine (3.29%), Vermont (2.39%), and Hawaii (1.93%). 

New Mutants

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September, has now been found in multiple other countries. There are 2,102 reported cases in the US as of 2/26/21. This isolate has now been found in 44 states and the District of Columbia. This isolate (let’s call it Lineage B.1.1.7 or SARS-CoV-2 UK) is more infectious than other previously circulating B2 lineage isolates. There are two deletions and six other mutations in its spike protein. One mutation involves a change of one amino acid, an asparagine at position 501 in the receptor binding motif with a tyrosine. This enhances binding (affinity) to the ACE-2 receptor and may alone be responsible for the increased infectivity of this isolate. Due to air and other travel, this isolate will become the dominant isolate worldwide. 

B.1.351, also known as the South African isolate, has 49 reported cases and has occurred in 15 states and the District of Columbia. The P.1 isolate (Brazil) has 16 reported cases and has been found in five states. (This data is available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html.)

A new, disturbing report out of the UK has found a second mutation in B.1.1.7. This mutation, which occurs in the loop sequence has also been found in the South African (B.1.351) and Brazilian (P.1) variants. (The loop sequence is in the receptor binding motif in the receptor binding domain of the S1 sequence of the spike protein.) This mutation involves a change of one amino acid of the spike protein, number 484, from glutamic acid to lysine. This point mutation allows the virus to bind better to the ACE2 receptor, which increases infectivity. People who are exposed to one of these variants (verus the old B2 isolate) are more likely to be infected and are more likely to transmit the virus to others. 

In our last two updates we summarized a research letter published in Clinical Infectious Diseases about a patient in the UK who was first infected in April with a B2 isolate and experienced only mild symptoms but was infected with the new B.1.1.7 variant in December and became critically ill. The patient described in this research letter was not protected by a natural infection with a B2 lineage SARS-CoV-2 isolate in April 2020 from having a potentially lethal second infection with a B.1.1.7 lineage variant in December 2020, suggesting that folks who have had a past SARS-CoV-2 infection should not expect to have any immunity to new variants such as B.1.1.7. All of the currently available vaccines were developed with spike protein from B2 lineages. Moderna, Pfizer, and AstraZeneca/Oxford are currently remaking their spike protein vaccines to address the mutations in the South African variant of SARS-CoV-2 because the AstraZeneca/Oxford vaccine did not work in a small trial in South Africa, where most of the patients had the South African mutant (B.1.351). 

A California Mutant

A fourth mutant isolate (CAL.20C) of SARS-CoV-2 has been identified in California. This isolate does not have any of the mutations mentioned above, but contains five mutations, three of which are in the spike protein, but not in the receptor binding motif. This mutant may be partially responsible for the massive increase in infections in California, to include infections of people who had already recovered from a SARS-CoV-2 infection earlier. In California to date, we have had 3,547,280 infections and 51,377 total deaths. California is averaging 357 deaths per day in the last 14 days. Currently, 8.76% of the population in California is infected. Nationally, we rank 26th in the percentage of people in the state infected. To my knowledge, only one privately held company is currently modifying their vaccine to cover the CAL.20C (California) mutant. 

Watching the Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments.

The Road Ahead

We are just on Day 38 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccine to vaccinate everyone who wants a vaccination by July 2021. Testing, wearing masks, social distancing and washing our hands frequently should no longer be political issues. These are non-pharmaceutical interventions used by most successful countries and some states to protect their citizens and their economies. New Zealand, Taiwan, and Australia are three countries that have done this successfully.  In the United States, Vermont and Hawaii are doing a better job handling the pandemic than many of our states. These interventions with vaccination should keep the pandemic from overwhelming our health care delivery system. New mutations will probably increase the numbers of infections occurring in the United States over the next 30 days. At least one mutant from the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This mutant may do the same thing in the USA.

The Pfizer and Moderna RNA vaccines are approved in the USA and the Johnson & Johnson single dose vaccination should be approved this weekend. The Oxford-AstraZeneca vaccine and Novavax vaccine should also be available in the second quarter of 2021. To vaccinate 80% of our population with two doses of a vaccine, we will need over 500 million doses of vaccine. The current goal of the Biden administration in the US is to vaccinate one million people each day for 100 days. The good news is that we are averaging 1.5 million vaccinations a day and have opened mass vaccination sites in multiple cities and states. 

The bad news is that all currently available vaccines are based on the Chinese spike protein sequence from December 2019. Mutated isolates, as discussed above, may overtake our ability to produce new vaccines and vaccinate the populace. Like Influenza vaccines, we may have to reformulate vaccines based on active, worldwide surveillance at least every 4 to 6 months. The FDA is currently putting together a guidance document for how to develop booster vaccines for SARS-CoV-2 mutations. A surrogate marker of protection like antibody to the mutated Receptor Binding Domains of SARS-CoV-2 should be considered for vaccine approval. 

We still need to perform more virus isolations and perform more DNA sequencing of viruses in each country, state, populous city, and county if we are to rapidly identify new mutations. I’m more hopeful that we will have the facilities, the equipment, and the trained staff needed to perform this work. As a nation we are finally preparing to make more vaccine, new vaccines directed against mutants, and the necessary rapid tests and protective equipment needed by medical staff, first responders, essential workers and especially teachers and students. I’m still hopeful we can work together on our and the world’s infectious disease problems. 

COVID-19

SARS-CoV-2 (COVID-19) Update

It’s time for our next 14-day moving average determinations and projections for infections and deaths from SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the Worldometers aggregators data set to make our projections of future total infections and deaths since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

In the United States, SARS-CoV-2 deaths have increased for the second time since the last 14-day period. There were 92 more deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 76,065 infections per day. This decrease in infections over the last two-week period may be because of a peak of infectivity of current circulating B2 lineage isolates. (B2 isolates are those that were most common in the first nine months of the pandemic.) On 1/29/21, 169,033 new infections occurred in the United States. There were also 3,652 deaths. The number of hospitalized patients is decreasing, and only 24,963 patients are critically ill. The number of critically ill patients has decreased by 3,887 in the last 14 days, while 45,575 new deaths occurred. This suggests that the number of critically ill patients is decreasing because a large number of patients are dying. 

As of 1/29/21, we have had 447,459 deaths and 26,512,193 SARS-CoV-2 infections in the United States. We have had 2,408,917 new infections in the last 14 days. We are adding over 1.2 million infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 1/29/21, sixteen states have had greater than 500,000 total infections, and 26 states had greater than 5,000 total deaths. 

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. In North Dakota 9.18% of the population was infected (ranked #1), and in South Dakota 8.03% of the population was infected (ranked #2).

As of 1/29/21, in the United States 8.00% of the population has had a documented SARS-CoV-2 infection. California was ranked 24th in infection percentage at 8.30%. In North Dakota 12.7% of the population was infected (ranked #1) and in South Dakota 12.2% of the population was infected (ranked #2). Forty-two states already have greater than 6% of their population infected (North Dakota, South Dakota, Iowa, Nebraska, Wisconsin, Utah, Montana, Illinois, Idaho, Tennessee, Rhode Island, Minnesota, Wyoming, Kansas, Indiana, Arkansas, Nevada, Alabama, Oklahoma, Mississippi, Arizona, New Mexico, Louisiana, Missouri, Georgia, Alaska, Florida, Texas, Connecticut, North Carolina, South Carolina, Colorado, Massachusetts, Ohio, New York, New Jersey, Delaware, Kentucky, West Virginia, Pennsylvania, California, and Michigan). 

New Mutants

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September, has now been found in multiple other countries. This isolate has now been found in over 25 states. This isolate (let’s call it Lineage B.1.1.7 or SARS-CoV-2 UK) is more infectious than other previously circulating B2 lineage isolates (probably 30 to 40% increased infectivity). There are two deletions and six other mutations in its spike protein. One mutation involves a change of one amino acid, an asparagine at position 501 in the receptor binding motif with a tyrosine. This enhances binding (affinity) to the ACE-2 receptor and may alone be responsible for the increased infectivity of this isolate. Due to air and other travel, this isolate should become the dominant isolate worldwide.  

In our last update we summarized a research letter published in Clinical Infectious Diseases about a patient in the UK who was first infected in April with a B2 isolate and experienced only mild symptoms but was infected with the new B.1.1.7 variant in December and became critically ill. The patient described in this research letter was not protected by a natural infection with a B2 lineage SARS-CoV-2 isolate in April 2020 from having a potentially lethal second infection with a B.1.1.7 lineage variant in December 2020, suggesting that folks who have had a past SARS-CoV-2 infection should not expect to have any immunity to new variants such as B.1.1.7. All of the currently available vaccines were developed with spike protein from B2 lineages, so it remains to be seen whether these vaccines will protect against B.1.1.7 infections or the additional isolates discussed below.

A second mutation in the loop sequence has been identified in the South African, Brazilian, and Japanese isolates. This mutation also enhances binding to the ACE-2 receptor and interferes with binding of antibodies to the SARS-CoV-2 receptor binding motif. This week, it was announced that in South Carolina, they have two unrelated patients infected with the South African mutant of SARS-CoV-2. Neither patient has traveled outside of South Carolina. According to the Director of the CDC, these represent community acquisition of the South African isolate. In addition, South Carolina announced today that they have identified the UK isolate B.1.1.7 in a patient in their state. Additionally, the state of Minnesota has reported, this week, the first case of the Brazilian mutant in the United States. 

A California Mutant

A fourth mutant isolate (CAL.20C) of SARS-CoV-2 has been identified in California. This isolate does not have any of the mutations mentioned above, but contains five mutations, three of which are in the spike protein, but not in the receptor binding motif. This mutant appears to be responsible for the massive increase in infections in California, to include infections of people who had already recovered from a SARS-CoV-2 infection earlier. In California, we have had 3,279,921 infections, 40,206 total deaths, and 6,378 deaths in the last 14 days. California is averaging 456 deaths per day in the last 14 days. Currently, 8.3% of the population in California is infected. Nationally, we rank 24th in the percentage of people in the state infected. 

Pfizer and Moderna announced this week that they would be reformulating their vaccines to cover the mutations in the South African isolate. To my knowledge, no company is currently modifying their vaccines to cover the CAL.20C (California) mutant. 

Watching the Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. 

The Road Ahead

We have a new President and Vice President. The President has made the pandemic a first priority. Testing, wearing masks, social distancing and washing our hands frequently should no longer be political issues. These are non-pharmaceutical interventions used by most successful countries and some states to protect their citizens and their economies. New Zealand, Taiwan, and Australia are three countries that have done this successfully.  In the United States, Vermont and Hawaii are doing a better job handling the pandemic than many of our states. The pandemic problem is overwhelming our health care delivery system in many states.

The Pfizer and Moderna RNA vaccines are both now approved in the USA. The Johnson & Johnson and Novavax vaccines are pending approval. To vaccinate 80% of our population with two doses of vaccine, we will need over 500 million doses of vaccine. Unless we start vaccine shipments to clinics and physicians’ offices, not just hospitals and pharmacies, I doubt most people will be able to receive any vaccine until April 2021. The current goal in the US is to vaccinate one million people each day for 100 days. At this rate, to vaccinate 280 million people will take 280 days—more than 9 months. 

All current vaccines are based on the Chinese spike protein sequence from December 2019. Mutated isolates, as discussed above, may overtake our ability to produce vaccines and vaccinate the populace. Like Influenza vaccines, we may have to reformulate vaccines based on active, worldwide surveillance every 8 to 12 months. We need to perform more virus isolations and perform more DNA sequencing of viruses in each country, state, populous city, and county if we are to rapidly identify new mutations. I’m not sure we have the facilities, the equipment, and the trained staff needed to perform this work. I feel we are not prepared (or preparing) to do this and will suffer the consequences if we continue down our current path.