COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections 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 eighth time in a 14-day period. There were 137 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 12,293 infections per day.  Our infections per day are still high, probably secondary to SARS-CoV-2 mutants, to include the Alpha/B.1.1.7 isolate, the Iota/B.1.526 isolate, the Epsilon/B.1.427 + B.1.429 isolate, the Beta/B.1.351 isolate, the Gamma/P.1 and Zeta/P.2 isolates, and the new isolate, Deta/B.1.617+. I would predict that the opening of schools, places of worship, bars, restaurants, indoor dining and travel all will contribute to further spread of multiple SARS-CoV-2 mutants and rising numbers  in infections, hospitalizations and deaths in the coming months. Increased traveling as well as summer vacations, and the July 4 holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden SARS-CoV-2 plan (day 136 of plan) will be necessary to stop spread of mutants and cause  further reductions in infections, hospitalizations and deaths in the future. On 6/04/21, 16,925 new infections occurred in the United States. There were also 520 deaths. The number of hospitalized patients is decreasing, but 5,631 patients are still seriously or critically ill. The number of critically ill patients has decreased by 1,761 in the last 14 days, while 6,577 new deaths occurred. The number of critically ill patients is decreasing for the fourth 14-day period, but a large number of patients are still dying each day. 

As of 6/04/21, we have had 612,249 deaths and 34,192,023 SARS-CoV-2 infections in the United States. We have had 271,267 new infections in the last 14 days. We are adding an average of 135,633 infections every 7 days. Each million infections usually results in 10,000 to 20,000 deaths. On 6/04/21, twenty-two states have had greater than 500,000 total infections, and 33 states have had greater than 5,000 total deaths. Nine states (Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York and California) have had greater than 35,000 deaths.

For comparison, 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 6/04/21, in the United States, 10.32% of the population has had a documented SARS-CoV-2 infection. In the last 6 months, over 6% of our country became infected with SARS-CoV-2. 

As of 6/04/21, California was still ranked 36th in infection percentage at 9.60%. In North Dakota 14.45% of the population was infected (ranked #1), while Rhode Island was at 14.34% (ranked #2) and South Dakota was at 14.04% of the population infected (ranked #3). Thirty-one states have greater than 10% of their population infected and 42 states have greater than 9% of their population infected. Only one state has less than 3% of their population infected: Hawaii (2.52%).

New Mutants

In a response for the need for “easy-to-pronounce and non-stigmatising labels,” at the end of May, the World Health Organization assigned a letter from the Greek alphabet to each SARS-CoV-2 variant. GISAID, Nextstrain, and Pango will continue to use the previously established nomenclature. For our purposes, we’ll be referring to each variant by both its Greek alphabet letter and the Pango nomenclature. 

The WHO has sorted variants into two categories: Variants of Concern (VOC) and Variants of Interest (VOI). The criteria for Variants of Concern are as follows:

  • Increase in transmissibility or detrimental change in COVID-19 epidemiology; or 
  • Increase in virulence or change in clinical disease presentation; or 
  • Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.  

The WHO categorizes the following four variants as Variants of Concern (VOC):

The criteria for Variants of Interest (VOI) are as follows:

  • has been identified to cause community transmission/multiple COVID-19 cases/clusters, or has been detected in multiple countries; OR  
  • is otherwise assessed to be a VOI by WHO in consultation with the WHO SARS-CoV-2 Virus Evolution Working Group. 

The WHO categorizes the following six variants as Variants of Interest (VOI):

A new mutant SARS-CoV-2 virus (lineage B.1.1.7, now referred to by WHO as Alpha), first seen in the UK in September 2020, has now been found in multiple other countries. This isolate has now been found in 50 states and the District of Columbia. This isolate 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. A study published March 10 in the British Medical Journal (BMJ) found that the risk of death increased by 64% in patients infected with the B.1.1.7 variant compared to all other isolates. Due to air and other travel, this isolate will become the dominant isolate worldwide. 

On 4/10/21, the CDC stopped providing data to the public on the number of reported cases of all variants of SARS-CoV-2, both nationally and by state. This data used to be available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html. The CDC claims that the data is available in its COVID-19 Data Tracker, but only percentages, not actual case numbers, are available, and the data ends on May 8, 2021.   

Luckily, GISAID is still reporting variant data. The United States has had more isolations of the Alpha variant (B.1.1.7) in the last four weeks (9,795) than any other country in the world, to include the United Kingdom. There have been a total of 160,842 cases of Alpha/B.1.1.7 identified in the US to date. (See chart below.)

At 1,842 cases, the United States has the fourth highest number of isolations of the Beta variant (B.1.351, first identified in South Africa), and 76 of these were in the last four weeks. 

And the United States has now surpassed Brazil for the most isolations of the Gamma variant (P.1) in the world, with 12,887 overall and 1,527 in the past four weeks. 

As for the Delta Variant (B.1.617+), the variant recently identified in India, only India and the United Kingdom have more isolated cases than in the United States, which has 1,888 total cases, 546 of which were identified in the last four weeks. 

The United States has also surpassed both the UK and Nigeria for the most isolations of the Eta varian (B.1.525) in the world, with 1,064 overall and 32 in the past four weeks. 

A disturbing report out of the UK has found a second mutation in Alpha/B.1.1.7. This mutation, which occurs in the loop sequence, has also been found in the Beta/B.1.351 and Gamma/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 (versus the old B2 isolate) are more likely to be infected and are more likely to transmit the virus to others. 

In our last three 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 Alpha/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 Alpha/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 Beta/B.1.351 mutant. 

New Mutant Delta/B.1.617+ Arrives in California

Stanford University announced five weeks ago that they have identified five infections with the Delta/B.1.617+ variant in the San Francisco Bay Area. There are actually three different B.1.617 variants: B.1.617.1, B.1.617.2 and B.1.617.3. The most common variant appears to be B.1.617.2. This isolate is a double-mutant responsible for greater than 50% of the infections in India. The data from India the last 14 days ending on 6/04/21 is still disturbing. India has had 2,541,685 infections in the last 14 days or an average of 181,549 infections per day. During this 14-day period India reported 59,354 deaths or 4,240 deaths per day. On May 21, 2021, India reported 121,476 new infections and 3,382 new deaths. On 6/04/21 the total deaths due to SARS-CoV-2 infections in India stood at 344,101. India, with a population of 1,390,456,911, has had only 2.06% of the country infected. Their hospitals are still running out of vaccines, oxygen, medications, beds and ventilators. Sadly a health disaster continues in the world’s most populous country. I would predict that prior SARS-CoV-2 infection in India or first generation SARS-CoV-2 vaccines will have a decreased effect on this mutant discussed in the next paragraph. 

Many of you may now be familiar with the E484K mutation present in the Beta/B.1.351 isolate, the Gamma/P.1 isolate, the Iota/B.1.526 isolate, and the double mutant Eta/B.1.525. When vaccine manufacturers make booster vaccines to address these variants, they will only account for the E484K mutation. What sets this Delta/B.1.617+ variant apart from the other variants is that it has a different point mutation at amino acid 484 that involves a change of one amino acid of the spike protein, number 484, from glutamic acid to glutamine (E484Q). This point mutation, like E484K, probably allows the virus to bind to the ACE2 receptor and evade neutralizing antibodies directed against the original Wuhan sequence. A vaccine created to address E484K would not address this isolate. 

The second mutation in Delta/B.1.617+ is L452R, which is one of the same mutations seen in Epsilon/B.1.427 + B.1.429. This mutation is also not being covered by any vaccine currently being made as a booster. It’s possible that people in California who were infected by the Epsilon mutant in the last six months might have some additional cross protective antibodies to Delta/B.1.617+.

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. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC, whose most recent data on variants is from May 8. 

LocationTotal Infections as of 6/04/21New Infections on 6/04/21Total DeathsNew Deaths on 5/21/21% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World173,713,909400,0753,736,0999,2832.22%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617+ (India)BV-1 (Texas, USA)NoNo
USA34,192,023
(ranked #1)
16,925
612,240
(ranked #1)
52010.32%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617+ (India)BV-1 (Texas, USA)NoNo
Brazil16,841,954(ranked #3)   38,482(ranked #2) 470,968(ranked #2)1,1847.87%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)NoNo
India28,693,835(ranked #2)121,476(ranked #1)344,101(ranked #3)3,3822.06%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOC 32421Delta/B.1.617+ (India)NoNo
United Kingdom4,506,016(ranked #7)6,238127,823116.60%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617+ (India)NoNo
California, USA3,794,271(ranked #10 in world)1,12963,395529..60%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617+ (India)NoNo
Mexico2,426,822(ranked #15)2,894228,362(ranked #4)2161.86%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617+ (India)NoNo
South Africa1,686,041(ranked #19)5,66856,832672.81%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617+ (India)NoNo
Canada1,389,508(ranked #23)2,06325,679353.65%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617+ (India)Yes, except Alberta ProvinceNo
Poland2,874,409(ranked #14)31774,101267.60%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617+ (India)NoNo
Turkey5,276,,468(ranked #5)6,16947,976946.19%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)NoNo
Russia5,108,129(ranked #6)8,947                                                   123,0373773.49%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617+ (India)NoNo
Argentina3,915,397(ranked #9)30,95080,4115388.59%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617+ (India)NoNo

*Also referred to as CAL.20C

SARS-CoV-2, Children, and MIS-C/PIMS

I’m pleased to see that COVID-19 cases and MIS-C (PIMS) cases in children in the US are finally getting national attention. The CDC now tracks total MIS-C cases and deaths in children and young adults up to 20 years old in the United States. As of June 2, CDC reported 4,018 cases of MIS-C that meet the case definition and 36 deaths—that’s 276 new cases and one new death since the May 3 report. The CDC notes, “As of October 1, the number of cases meeting the case definition for multisystem inflammatory syndrome in children (MIS-C) in the United States surpassed 1,000. As of February 1, this number surpassed 2,000, and exceeded 3,000 as of April 1.” This means it took seven months to reach 1,000 MIS-C cases, only four months to reach an additional 1,000 cases, and only two months to add an additional 1,185 cases. This suggests to us that Alpha/B.1.1.7 is causing more MIS-C. 

Date of ReportingTotal MIS-C PatientsChange Since Last ReportTotal MIS-C DeathsChange Since Last Report
6/2/20214018+27636+1
5/3/20213742+55735-1
3/29/20213185+56836+3
3/1/2021261733

Schools in the United States have been open throughout the pandemic, with teachers and education support professionals demonstrating their extraordinary ability to adapt in adverse circumstances. Teachers all over the country reinvented their teaching, taking their classrooms online in order to provide safe and remote learning experiences for students. The so-called “reopening” of schools, which more accurately refers to the opening of school buildings, as schools never closed, has been highly politicized, with many governors issuing mandates for in-person instruction, even as case counts, hospitalizations, and deaths in their states rose exponentially. The CDC has maintained that transmission risk in schools is minimal, provided that adequate safety measures are taken; however, we know that many states have not properly enforced universal masking (and some are repealing mask mandates this week), and we know that many school facilities are not equipped with the proper air handling systems. With more school buildings opening, there is a growing body of research that suggests that COVID-19 transmission can and does happen in schools. 

After recommending for months that school buildings be open, in mid-February (a year into the pandemic), The American Academy of Pediatrics, in collaboration with the Children’s Hospital Association, finally began tracking data on COVID-19 in children at the state and national level. Data reporting by states is still voluntary, and every state is different in its willingness to collect and disclose data on infections, hospitalizations, deaths, and testing rates in children. 

As of the APA’s May 27 report, only 11 states provide age distribution for testing. This makes it difficult to hold states accountable for testing each age group in proportion to its population. We’ve seen a trend in states where testing data with age distribution is available that children are tested at lower rates than adults. Hospitalization data by age group is only available in 24 states and New York City, so we only understand the severity of COVID-19 infections in children for about half the country. Age distribution for cases is provided by 49 states, New York City, the District of Columbia, Puerto Rico, and Guam. Age distribution for deaths is provided in 43 states, New York City, Puerto Rico, and Guam. It’s worth noting that New York State does not provide age data for cases, testing, hospitalizations, and deaths. Two states, Florida and Utah, only report cases in children aged 0-14, so the number of cases, hospitalizations, and deaths in children ages 15-17 is unknown in these states. 

As of May 27, A total of 322 child deaths due to COVID-19 were reported in 43 states (an increase of 6 child deaths in one week). In the United States, The following states do not report child mortality due to COVID-19: Michigan, Montana, New Mexico, New York, Rhode Island, South Carolina, and West Virginia. Texas only reports age data for 3% of confirmed COVID-19 cases, so state-level data from Texas is extremely limited for assessing the incidence of COVID-19 in children. Even considering this, Texas reported 52 child deaths. Arizona reported 33, California 23, Colorado 15 (+2), Florida 7, Georgia 10, Illinois 18, Maryland 10, Tennessee 10, Massachusetts 8 (+1), Pennsylvania 11, and New York City 24. 

If we truly want to keep children safe, especially as many school buildings open for in-person instruction, we need to collect more complete data in every state on child testing rates, cases, hospitalizations, and deaths.

The New York Times reports that nationally, children 12 and up have higher vaccination rates than the general population, with 50% of children 12 and up vaccinated, and 53% of children 18 and up fully vaccinated, according to the CDC.

However, some states are falling far behind when it comes to getting children—and the general population—fully vaccinated. Idaho, Alabama, Mississippi, and Louisiana have given at least one shot to less than 10% of children 12-17 years old. Massachusetts, Hawaii, and Vermont are the only three states that have given at least one shot to at least 50% of children 12-15. California has given at least one shot to 36% of children 12-17 years old. 

The Road Ahead

We are on Day 122 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccines to vaccinate everyone who wants a vaccination by July 2021. As of 6/5/21, 170.8 million people (approximately 51.5% of the population) have had one dose of any vaccine. 138.9 million people (41.9% of the population) are fully vaccinated. 

As of May 10, all people in the U.S. over the age of 12 are eligible to receive a vaccine. The Biden administration has already exceeded its goal of administering 200 million doses of vaccine in the first 100 days of the administration. The Pfizer-BioNtech is already approved for ages 12-15 and the Moderna vaccine should be approved in June 2021. Moderna has applied for emergency use authorization to administer their mRNA vaccines to children aged 12-15. Testing is ongoing for children in younger age groups and may be approved for ages 2-11 by the end of September 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, Hawaii is doing a better job handling the pandemic than many of our states. These interventions and vaccination should keep the pandemic from overwhelming our health care delivery systems world-wide. New mutations like Epsilon/B.1.427 + B.1.429 and the Alpha, Beta, Gamma, and Delta variants will probably spread rapidly throughout the United States over the next 90 days as many states (ex. Texas, Florida, Iowa, Mississippi, Wyoming and South Carolina) open up everything and do away with masking and social distancing. We will probably see increased new infections per day in the United States. In the UK, Alpha/B.1.1.7, has increased the number of infections, hospitalizations and deaths. This and other mutants may do the same thing in the USA.

The Pfizer and Moderna RNA vaccines and the Johnson & Johnson single dose vaccination adenovirus vaccine are all being used to immunize people in the USA. The Oxford-AstraZeneca vaccine and the Novavax vaccine may be available in the fourth quarter of 2021. 

The bad news is that all currently available vaccines are based on the spike protein sequence identified in China in 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. 

The ideal approach to addressing the major mutations on at least five continents would be to make vaccines against each of the mutations. I’d get all of the vaccine companies and contract production companies on a call and “suggest” that two companies at least make and mass produce one of the four mutations. The government would pay the cost and buy at least 200 million doses in advance for each variant at say $40 a dose. The total cost to purchase the vaccine (800 million doses) would only be 32 billion dollars. Give each company a billion dollars each for development costs (another 8 billion dollars). Spend another two billion dollars for syringes and you’ve got enough booster doses to vaccinate 200 million people for all 4 variants. 42 billion dollars would be a small price to pay to catch up with the current mutations. Even if you had to do this every two years, it would be well worth the dollars spent. 

We are not doing adequate numbers of PCR or antigen detection assays in the United States. According to JHU, in January of 2021, we were doing up to 2,307,949 tests per day. In March 2021, the highest number of tests per day was 1,709,210, and in April, the highest number of tests per day was 2,008,319. Currently, we’re doing 710,675 tests per day (7-day moving average); that’s 1,297,644 fewer tests per day than the April high. 

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 still need to make and distribute more vaccines to other countries, 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. 

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections 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 sixth time in a 14-day period. There were 96 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 17,267 infections per day.Our infections per day are still high, probably secondary to SARS-CoV-2 mutants, to include the B.1.1.7 (UK isolate), a New York isolate B.1.526, the CAL.20C isolate, the South African isolate B.1.351, the Brazilian isolates P.1 and P.2, and the new Indian isolate B.1.617. I would predict that the opening of schools, places of worship, bars, restaurants, indoor dining and travel all will contribute to further spread of multiple SARS-CoV-2 mutants and rising numbers  in infections, hospitalizations and deaths in the coming months. Increased traveling as well as upcoming Memorial Day weekend, summer vacations, and the July 4 holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden SARS-CoV-2 plan (day 122 of plan) will be necessary to stop spread of mutants and cause  further reductions in infections, hospitalizations and deaths in the future. On 5/21/21, 29,014 new infections occurred in the United States. There were also 603 deaths. The number of hospitalized patients is decreasing, but 7,392 patients are still seriously or critically ill. The number of critically ill patients has decreased by 1,748 in the last 14 days, while 8,497 new deaths occurred. The number of critically ill patients is decreasing for the third 14 day period but a large number of patients are still dying each day. 

As of 5/21/21, we have had 603,408 deaths and 33,862,398 SARS-CoV-2 infections in the United States. We have had 443,372 new infections in the last 14 days. We are adding an average of 221,686 infections every 7 days. Each million infections usually results in 10,000 to 20,000 deaths. On 5/21/21, twenty-two states have had greater than 500,000 total infections, and 33 states have had greater than 5,000 total deaths. Nine states (Michigan, Georgia, Illinois, New Jersey, Pennsylvania,Florida, Texas, New York and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York and California) have had greater than 35,000 deaths.

For comparison, 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 5/21/21, in the United States, 10.17% of the population has had a documented SARS-CoV-2 infection. In the last 6 months, over 6% of our country became infected with SARS-CoV-2. 

As of 5/21/21, California was still ranked 36th in infection percentage at 9.55%. In North Dakota 14.30% of the population was infected (ranked #1), while Rhode Island was at 14.27% (ranked #2) and South Dakota was at 14.00% of the population infected (ranked #3). Thirty-one states have greater than 10% of their population infected and 41 states have greater than 9% of their population infected. Only one state has less than 3% of their population infected: Hawaii (2.52%). Ten states still have greater than 1,000 new infections per day with Florida leading again on 5/21/21 with 2,371 infections.

New Mutants

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September 2020, has now been found in multiple other countries. There are 3,170 reported cases in the USA as of 3/11/21, 8337 cases as of 3/25/21 and 20,915 cases as of 4/10/21 in the US. This isolate has now been found in 50 states and the District of Columbia. This isolate 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. A study published March 10 in the British Medical Journal (BMJ) found that the risk of death increased by 64% in patients infected with the B.1.1.7 variant compared to all other isolates. Due to air and other travel, this isolate will become the dominant isolate worldwide. 

On 4/10/21, the CDC stopped providing data to the public on the number of reported cases of all variants of SARS-CoV-2, both nationally and by state. This data used to be available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html. The CDC claims that the data is available in its COVID-19 Data Tracker, but only percentages, not actual case numbers, are available, and the data ends on April 10, 2021.   

Luckily, GISAID is still reporting variant data. The United States has had more isolations of B.1.1.7 in the last four weeks (15,909) than any other country in the world, to include the United Kingdom. There have been a total of 132,214 cases of B.1.1.7 identified in the US to date. 22,300 have occurred in the last 4 weeks. (See chart below.)

At 191 cases, the United States has the fourth highest number of isolations of B.1.351 (the South African variant) in the last four weeks and a total of 1,564 isolations. 

And the United States has now surpassed Brazil for the most isolations of P.1 in the world, with 10,362 overall and 3,003 in the past four weeks. 

As for B.1.617, the variant recently identified in India, only India and the United Kingdom have more isolated cases than in the United States, which has 1,051 total cases, 506 of which were identified in the last four weeks. 

The United States has also surpassed both the UK and Nigeria for the most isolations of B.1.525 in the world, with 938 overall and 109 in the past four weeks. 

A 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 (versus the old B2 isolate) are more likely to be infected and are more likely to transmit the virus to others. 

In our last three 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 of SARS-CoV-2, B.1.429 + B.1.427 (CAL.20C), is the predominant mutation 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 3,775,758 infections and 62,858 total deaths. California is averaging 45 deaths per day in the last 14 days, which is a 13 deaths per day decrease from the preceding 14 day period. Currently, 9.55% of the population in California is infected. Nationally, we rank 35th 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 B.1.429 + B.1.427 mutant. 

New Indian Mutant B.1.617 Arrives in California

Stanford University announced five weeks ago that they have identified five infections with the Maharashtra India VOC 32421 (new variant designation B.1.617) in the San Francisco Bay Area. There are actually three different B.1.617 variants: B.1.617.1, B.1.617.2 and B.1.617.3. The most common variant appears to be B.1.617.2 This isolate is a double-mutant responsible for greater than 50% of the infections in India. The data from India the last 14 days ending on 5/21/21 is still disturbing. India has had 4,398,458 infections in the last 14 days or an average of 314,176 infections per day. During this 14-day period India reported 57,243 deaths or 4,089 deaths per day. On May 21, 2021, India reported 254,395 new infections and 4,143 new deaths. On 5/21/21 the total deaths due to SARS-CoV-2 infections in India stood at 295,508. India, with a population of 1,390,456,911, has had only 1.88% of the country infected. Their hospitals are still running out of vaccines, oxygen, medications, beds and ventilators. Sadly a health disaster continues in the world’s most populous country. I would predict that prior SARS-CoV-2 infection in India or first generation SARS-CoV-2 vaccines will have a decreased effect on this mutant discussed in the next paragraph. 

Many of you may now be familiar with the E484K mutation present in the South African isolate, the Brazilian isolate, the New York isolate (B.1.256), and the new Nigerian/UK double mutant. When vaccine manufacturers make booster vaccines to address these variants, they will only account for the E484K mutation. What sets this Maharashtra India B.1.617 variant apart from the other variants is that it has a different point mutation at amino acid 484 that involves a change of one amino acid of the spike protein, number 484, from glutamic acid to glutamine (E484Q). This point mutation, like E484K, probably allows the virus to bind to the ACE2 receptor and evade neutralizing antibodies directed against the original Wuhan sequence. A vaccine created to address E484K would not address this isolate. 

The second mutation in Maharashtra India VOC B.1.617 is L452R, which is one of the same mutations seen in CAL.20C (B.1.429 + B.1.427). This mutation is also not being covered by any vaccine currently being made as a booster. It’s possible that people in California who were infected by the Cal.20C mutant in the last six months might have some additional cross protective antibodies to B.1.617.

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. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC, whose most recent data on variants is from May 8. 

LocationTotal Infections as of 5/21/21New Infections on 5/21/21Total DeathsNew Deaths on 5/21/21% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World166,465,183621,0483,457,50012,7782.13%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.526 (USA-NYC)B.1.351 (SA)B.1.429 + B.1.427 (USA)*P.1 (Brazil)P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421B.1.617+ (India)BV-1 (Texas, USA)NoNo
USA33,862,398
(ranked #1)
29,014
(ranked #4)
603,408
(ranked #1)
65710.17%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.526 (USA-NYC)B.1.351 (SA)B.1.429 + B.1.427 (USA)*P.1 (Brazil)P.2 (Brazil)B.1.617+ (India)BV-1 (Texas, USA)NoNo
Brazil15,976,156(ranked #3)   77,598(ranked #2) 446,521(ranked #2)2,1367.46%B2 lineageB.1.1.7 (UK)B.1.351 (SA)P.1 (Brazil)P.2 (Brazil)NoNo
India26,285.069(ranked #2)254,395(ranked #1)295,508(ranked #3)4,1431.88%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)*B.1.525 (Nigeria/UK)APTK India VOC 32421B.1.617+ (India)NoNo
United Kingdom4,457,752(ranked #7)2,829127,71096.53%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)*P.1 (Brazil)B.1.617+ (India)NoNo
California, USA3,775,758(ranked #9 in world)1,22362,858469.55%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)*P.2 (Brazil)B.1.617+ (India)NoNo
Mexico2,390,140(ranked #15)2,628221,080(ranked #4)2301.83%B2 lineageB.1.1.7 (UK)B.1.429 + B.1.427 (USA)*P.1 (Brazil)B.1.617+ (India)NoNo
South Africa1,628,335(ranked #20)3,33255,7191512.71%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.617+ (India)NoNo
Canada1,352,121(ranked #22)4,67625,162513.55%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.429 + B.1.427 (USA)*P.1 (Brazil)B.1.617+ (India)Yes, except Alberta ProvinceNo
Poland2,863,030(ranked #13)1,67872,6911917.57%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.617+ (India)NoNo
Turkey5,169,951(ranked #5)9,52845,8402146.07%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)NoNo
Russia4,983,845(ranked #6)8,937117,7393783.41%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.617+ (India)NoNo
Argentina3,482,512(ranked #11)35,46835,4686927.64%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.1 (Brazil)B.1.617+ (India)NoNo

*Also referred to as CAL.20C

SARS-CoV-2, Children, and MIS-C/PIMS

I’m pleased to see that COVID-19 cases and MIS-C (PIMS) cases in children in the US are finally getting national attention. The CDC now tracks total MIS-C cases and deaths in children and young adults up to 20 years old in the United States. As of May 3, CDC reported 3,742 cases of MIS-C that meet the case definition and 35 deaths—that’s 557 new cases and no new deaths since the March 29 report. The CDC notes, “As of October 1, the number of cases meeting the case definition for multisystem inflammatory syndrome in children (MIS-C) in the United States surpassed 1,000. As of February 1, this number surpassed 2,000, and exceeded 3,000 as of April 1.” This means it took seven months to reach 1,000 MIS-C cases, only four months to reach an additional 1,000 cases, and only two months to add an additional 1,185 cases. This suggests to us that B.1.1.7 is causing more MIS-C. We’re averaging over 500 new cases of MIS-C each month for the last two months, despite decreases in the number of SARS-CoV-2 infections in the United States. 

Date of ReportingTotal MIS-C PatientsChange Since Last ReportTotal MIS-C DeathsChange Since Last Report
5/3/20213742+55735-1
3/29/20213185+56836+3
3/1/2021261733

Schools in the United States have been open throughout the pandemic, with teachers and education support professionals demonstrating their extraordinary ability to adapt in adverse circumstances. Teachers all over the country reinvented their teaching, taking their classrooms online in order to provide safe and remote learning experiences for students. The so-called “reopening” of schools, which more accurately refers to the opening of school buildings, as schools never closed, has been highly politicized, with many governors issuing mandates for in-person instruction, even as case counts, hospitalizations, and deaths in their states rose exponentially. The CDC has maintained that transmission risk in schools is minimal, provided that adequate safety measures are taken; however, we know that many states have not properly enforced universal masking (and some are repealing mask mandates this week), and we know that many school facilities are not equipped with the proper air handling systems. With more school buildings opening, there is a growing body of research that suggests that COVID-19 transmission can and does happen in schools. 

After recommending for months that school buildings be open, in mid-February (a year into the pandemic), The American Academy of Pediatrics, in collaboration with the Children’s Hospital Association, finally began tracking data on COVID-19 in children at the state and national level. Data reporting by states is still voluntary, and every state is different in its willingness to collect and disclose data on infections, hospitalizations, deaths, and testing rates in children. 

As of the APA’s May 20 report, only 11 states provide age distribution for testing. This makes it difficult to hold states accountable for testing each age group in proportion to its population. We’ve seen a trend in states where testing data with age distribution is available that children are tested at lower rates than adults. Hospitalization data by age group is only available in 24 states and New York City, so we only understand the severity of COVID-19 infections in children for about half the country. Age distribution for cases is provided by 49 states, New York City, the District of Columbia, Puerto Rico, and Guam. It’s worth noting that New York State does not provide age data for cases, testing, hospitalizations, and deaths. Two states, Florida and Utah, only report cases in children aged 0-14, so the number of cases, hospitalizations, and deaths in children ages 15-17 is unknown in these states. 

As of May 20, A total of 316 child deaths due to COVID-19 were reported in 43 states (an increase of 8 child deaths in one week). In the United States, The following states do not report child mortality due to COVID-19: Michigan, Montana, New Mexico, New York, Rhode Island, South Carolina, and West Virginia. Texas only reports age data for 3% of confirmed COVID-19 cases, so state-level data from Texas is extremely limited for assessing the incidence of COVID-19 in children. Even considering this, Texas reported 52 child deaths. Arizona reported 33 (+2), California 23 (+2), Colorado 13, Florida 7 (+1), Georgia 10, Illinois 18, Maryland 10, Tennessee 10, Massachusetts 7 (+2), Pennsylvania 11 (+1), and New York City 24. 

If we truly want to keep children safe, especially as many school buildings open for in-person instruction, we need to collect more complete data in every state on child testing rates, cases, hospitalizations, and deaths.

The Road Ahead

We are on Day 122 of the Biden-Harris administration.The President has made the pandemic a first priority and has now ordered enough vaccines to vaccinate everyone who wants a vaccination by July 2021. As of 5/24/21, 164.3 million people have had one dose of any vaccine. 131 million people are fully vaccinated. 

As of May 10, all people in the U.S. over the age of 12 are eligible to receive a vaccine. The Biden administration has already exceeded its goal of administering 200 million doses of vaccine in the first 100 days of the administration. The Pfizer-BioNtech is already approved for ages 12-15 and the Moderna vaccine should be approved in June 2021. Moderna has applied for emergency use authorization to administer their mRNA vaccines to children aged 12-15. Testing is ongoing for children in younger age groups and may be approved for ages 2-11 by the end of September 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, Hawaii is doing a better job handling the pandemic than many of our states. These interventions and vaccination should keep the pandemic from overwhelming our health care delivery systems world-wide. New mutations like B.1.429 + B.1.427 (Cal.20C) and the UK, Brazillian, South African, and Indian variants will probably spread rapidly throughout the United States over the next 90 days as many states (particularly in Texas, Florida, Iowa, Mississippi, Wyoming and South Carolina) open up everything and do away with masking and social distancing. We will probably see increased new infections per day in the United States. In the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This and other mutants may do the same thing in the USA.

The Pfizer and Moderna RNA vaccines and the Johnson & Johnson single dose vaccination adenovirus vaccine are all being used to immunize people in the USA. The Oxford-AstraZeneca vaccine and Novavax vaccine may be available in the fourth quarter of 2021. 

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. 

The ideal approach to spreading major mutations on at least five continents would be to make vaccines against each of the mutations. I’d get all of the vaccine companies and contract production companies on a call and “suggest” that two companies at least make and mass produce one of the four mutations. The government would pay the cost and buy at least 200 million doses in advance for each variant at say $40 a dose. The total cost to purchase the vaccine (800 million doses) would only be 32 billion dollars. Give each company a billion dollars each for development costs (another 8 billion dollars). Spend another two billion dollars for syringes and you’ve got enough booster doses to vaccinate 200 million people for all 4 variants. 42 billion dollars would be a small price to pay to catch up with the current mutations. Even if you had to do this every two years, it would be well worth the dollars spent. 

We are not doing adequate numbers of PCR or antigen detection assays in the United States. According to JHU, in January of 2021, we were doing up to 2,307,949 tests per day. In March 2021, the highest number of tests per day was 1,709,210, and in April, the highest number of tests per day was 2,008,319. Currently, we’re doing 975,589 tests per day (7-day moving average); that’s 453,963 fewer tests per day than the April high. 

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 still need to make and distribute more vaccines for other countries, 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. 

What Our Team Is Reading This Week

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. 

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 Worldometer 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.

14-day Moving Averages of SARS-CoV-2  Deaths and Infections in USA

1/15/211/01/2112/18/2012/04/2011/21/2011/07/2010/24/2010/10/209/26/209/12/208/28/208/14/207/31/207/17/20
Deaths/day3,163*2,4622,5101,7771,2868917547287878239631,0501,070714
Infections/Day248,131**186,106216,750173,513154,94590,07559,15545,24640,65739,95143,88454,59766,74861,512
*701 more deaths per day than the 14-day period ending in 1/1/21 **62,025 more infections per day than the 14-day period ending in 1/1/21

In the United States, SARS-CoV-2 deaths have increased for the first time since the last 14-day period. There were 701 more deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 62,024 infections per day.  This increase in infections over the last two-week period is due to two major holidays. On 1/15/21, 248,080 new infections occurred in the United States. There were also 3,805 deaths. Over 130,000 people are hospitalized in the USA and 28,937 serious or critically ill patients are in our hospitals as of 1/15/21.

As of 1/15/21, we have had 401,856 deaths and 24,102,429 SARS CoV-2 infections in the United States.  We have had 3,473,834 new infections in the last 14 days. We are adding  over 1.7 million infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 1/15/21, fifteen 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 1/15/21, in the United States 7.28% of the population has had a documented SARS-CoV-2 infection. California was ranked 26th in infection percentage at 7.40%. In North Dakota 12.54% of the population was infected (ranked #1) and in South Dakota 11.86% of the population was infected (ranked #2). Thirty-six 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, Colorado, Massachusetts, Ohio, New Jersey, Delaware and Kentucky). 

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. In California, two patients in LA county and three patients in San Diego county are infected with this new mutant. Two patients in Colorado and one in Florida have also been identified as of 12/31/20. As of 1/15/21, this new mutant has been found in nine other states (New York, Georgia, Texas, Connecticut, Pennsylvania, Ohio, Utah, Maryland, and Wisconsin. 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 a research letter pending publication in Clinical Infectious Diseases, a group of NHS doctors describe the case of a patient who was first infected with SARS-CoV-2 in April and became reinfected in December. After the patient’s second infection, Whole Genome Sequencing (WGS) was performed on samples from both instances of infection, and it was determined that the first infection in April was with a B.2 lineage variant and the second infection was with the new B.1.1.7 variant. While the patient, “a 78 year old man with a history of Type 2 Diabetes Mellitus, diabetic nephropathy on haemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnoea, ischaemic heart disease, with no history of immunosuppression” had only had a mild illness (fever being the only symptom) during the first infection, during the second infection, he had much more severe symptoms, including shortness of breath and hypoxia, which led to emergency intubation. He developed “Severe Covid-19 pneumonia complicated by mycocardial infarction with resulting trifascicular block and Atrio-Ventricular (AV) dissociation and pulmonary oedema.” (To read the full research letter, visit https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab014/6076528 and click PDF.)

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 week. This mutation will also enhance binding to the ACE-2 receptor and may interfere with binding of monoclonal antibodies to the SARS-CoV-2 receptor binding motif. If this rate of mutations and deletions continues in the spike protein, especially in the receptor binding domain and motif, in my opinion, then vaccine reformulation will be required in 2021.

We have a new President-elect and Vice President-elect, now confirmed by the electoral college and approved in the House and Senate on 1/06/21 despite a riot and invasion of the Capital by President Trump’s supporters. The President-elect has made the pandemic a first priority after Inauguration on January 20, 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, Maine, 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. Unless things change before Inauguration Day on January 20, 2020 (5 days away) we could, by our predictions, have an additional 1,221,405 SARS-CoV-2 infections and another 15,815 deaths. Our infections per day and deaths per day will continue to increase for at least another 8 to 12 weeks.

The Pfizer and Moderna RNA vaccines are both now approved in the USA. 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.  

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. “Magical thinking” will not solve these problems, just laborious work by many people. Are we all up to the tasks at hand?

COVID-19, Uncategorized

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. 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.

14-day moving averages of SARS-CoV-2 Deaths and Infections in the USA

11/21/2011/07/2010/24/2010/10/209/26/209/12/208/28/208/14/20
Average deaths per day1,286*8917547287878239631,050
Average infections per day154,945**90,07559,15545,24640,65739,95143,88454,597
*395 more deaths per day than 11/07/20 **64,870 more infections per day than 11/07/20

In the United States, SARS-CoV-2 deaths have increased for the third time in a 14-day period after decreasing in each of five previous 14-day periods. There were 395 more deaths per day in the last 14 days. In the last 14 days, the number of infections has increased by 64,870 infections per day. Deaths per day will continue to increase at least over the next 8 to 10 weeks. On 11/20/20, 204,179 new infections occurred in the United States, another new daily record for infections. There were also 1,999 deaths and 22,789 serious or critically ill patients in our hospitals on 11/20/20.

As of 11/20/20 we have had 260,331 deaths and 12,277,827 SARS CoV-2 infections in the United States. This represents 21.2% of the infections and 18.9% of the deaths in the world from SARS-CoV-2. We have had 2,169,236 new infections in the last 14 days. We are adding one million infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 11/20/20, thirty five states had greater than 100,000 total infections and 29 states had greater than 2,000 total deaths. Only 58 other countries have greater than 100,000 infections and only 51 countries have more than 2,000 deaths.

We have a new President-elect and Vice President-elect that are making the pandemic a first priority after Inauguration on January 20, 2021. Testing, contact tracing, 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, Maine, 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. Unless things change before Inauguration Day on January 20, 2020 (61 days away) we could by our predictions have an additional 9,451,645 SARS-CoV-2 infections and another 78,446 deaths. If our infections per day and deaths per day continue to increase these numbers will, once again, be underestimations of the problem.

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. 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.

11/07/2010/24/2010/10/209/26/209/12/208/28/208/14/207/31/20
Average Deaths per day*8917547287878239631,0501,070
Average Infections per day**90,07559,15545,24640,65739,95143,88454,59766,748
*137 more deaths per day than 10/24/20 14-day period
**30,920 more infections per day than 10/24/20 14-day period

In the United States, SARS-CoV-2 deaths have increased for the second time in a 14-day period after decreasing in each of five previous 14-day periods. There were 137 more deaths per day in the last 14 days. In the last 14 days, the number of infections per day has increased by 30,920. Deaths per day will continue to increase at least over the next 8 to 12 weeks. On 11/06/20, 132,540 new infections occurred in the United States, another new daily record for infections. There were also 1,248 deaths and 18,303 serious or critically ill patients in our hospitals on 11/06/20.

As of 11/06/20, we have had 242,230 deaths and 10,058,586 SARS-CoV-2 infections in the United States. This represents 20.2% of the infections and 19.4% of the deaths in the world from SARS-CoV-2. On 10/24/20, 29 states in the United States had greater than 100,000 infections and 26 states had greater than 2,000 deaths. On 11/06/20, 32 states have greater than 100,000 infections and 28 states have greater than 2,000 deaths. Only 57 other countries have greater than 100,000 infections, and only 45 countries have more than 2,000 deaths.

As of 10/24/20, in the United States, 2.642% of the population has had a documented SARS-CoV-2 infection. California was ranked 33rd in infection percentage at 2.270%. In North Dakota, 4.716% of the population was infected (ranked #1) and in South Dakota 4.205% of the population was infected (ranked #2). As of 11/06/20, in the United States, 3.038% of the population has had a documented SARS-CoV-2 infection. California was ranked 36th in infection percentage at 2.44%. In North Dakota 6.77% of the population was infected (ranked #1) and in South Dakota 5.95% of the population was infected (ranked #2). On 11/06/20, Texas became the first state to record over a million total infections. They had 9,239 infections and 124 deaths on 11/06/20, bringing their total infections to 1,007,155 and total deaths to 19,154. 3.47% of Texas residents have had an infection. Probably greater than 90% of the people in the USA have not had their first SARS-CoV-2 infection.

We have a new President-elect and Vice President-elect today. Testing, contact tracing, 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, Maine, Vermont, New Hampshire, Hawaii and Oregon are doing a better job handling the pandemic than many of our states. The pandemic problem is about to overwhelm our health care delivery system in many states. Unless things change before Inauguration Day on January 20, 2021 (75 days away) we could, by our predictions, have 6,755,625 new SARS-CoV-2 infections and another 66,825 deaths. If our infections per day and deaths per day continue to increase, these numbers will be underestimations of the problem.

COVID-19

SARS-CoV-2 (COVID-19) Projections

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. 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.

14-day moving averages of SARS-CoV-2 Deaths and Infections

10/10/209/26/209/12/208/28/208/14/20
Average deaths per day728*7878239631,050
Average infections per day45,246**40,65739,95143,88454,597
*59 fewer deaths per day than 9/26/20 **4,589 more infections per day than 9/26/20

In the United States, SARS CoV-2 deaths have decreased in each of the last five previous 14-day periods. There were 59 fewer deaths per day in the last 14 days.  However, in the last 14 days the number of infections has increased by 4,589 infections per day. Deaths per day should increase over the next 2 to 3 weeks.

As of 10/09/20 we have had 218,647 deaths and 7,894,478  SARS CoV-2 infections in the United States. This represents 21.3% of the infections and 20.4% of the deaths in the world from SARS-CoV-2. Twenty-four states in the United States have greater than 100,000 infections, and 26 states have greater than 2,000 deaths. Only 43 other countries have greater than 100,000 infections and only 41 countries have more than 2,000 deaths.

COVID-19

SARS-CoV-2 (COVID-19) Projections

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. 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.

 14-day moving averages of SARS-CoV-2  deaths and infections

9/26/209/12/208/28/208/14/207/31/20
Average Deaths Per Day7878239631,0501,070
Average Infections Per Day40,65739,95143,88454,59766,748
*36 fewer deaths per day than on 9/12/20 **706 more infections per day than 9/12/20

In the United States the SARS-CoV-2 deaths have decreased in each of the last four previous 14-day periods. There were 36 fewer deaths per day in the last 14 days. However, in the last 14 days, the number of infections has increased by 706 infections per day.

As of 9/26/20 we have had 208,440 deaths and 7,244,184 SARS-CoV-2 infections in the United States. This represents 22% of the infections and 21% of the deaths in the world from SARS-CoV-2. Twenty-two states in the United States have greater than 100,000 infections and 26 states have greater than 2,000 deaths. Only 37 other countries have greater than 100,000 infections and only 38 countries have more than 2,000 deaths.

Our new projections for the United States are that by October 4, 2020, we will have had 214,696 total deaths and 7,569,440 infections.

Our new projections for the United States are that by November 4, 2020, we will have had 239,093 total deaths and 8,829,807 total infections.

COVID-19

SARS-CoV-2 Projections 9/14/20

It’s time for our next 14-day moving average determinations and projections for infections and deaths from SARS-CoV-2 (COVID-19) for the United States. 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.

14-Day Moving Averages of SARS-CoV-2 Infections and Deaths

9/12/208/28/208/14/207/31/207/17/20
Average Deaths per day823*9631,0501,070714
Average Infections per day39,951**43,88454,59766,74861,512
*140 fewer deaths/day than 8/28/20 **3,933 fewer infections/day than 8/28/20

The SARS-CoV-2 infections and subsequent deaths have decreased in each of three previous 14-day periods. In the last 14 days, the number of infections has decreased by 3,933 infections per day, and average deaths per day have decreased by 140 deaths per day.

As of 9/11/20 we have had 197,177 deaths and 6,636,247 SARS-CoV-2 infections in the United States.

Our new projections for the United States are that by October 4, 2020 we will have had 211,283 total deaths and 7,507,249 infections.

Our new projections for the United States are that by November 4, 2020 we will have had 241,734 total deaths and 8,972,116 total infections.

COVID-19

SARS-CoV-2 (COVID-19) Projections

It’s time for our next 14-day moving average determinations and projections for infections and deaths from SARS-CoV-2 (COVID-19) for the United States. 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.

14-Day Moving Averages of SARS-CoV-2 Deaths and Infections

8/28/208/14/207/31/207/17/20
Average deaths per day963*1,0501,070714
Average infections per day43,884**54,59766,74861,512
*87 fewer deaths per day than 8/14/20 **10,713 fewer infections per day than 8/14/20

The SARS-CoV-2 infections and subsequent deaths were decreasing in each of two previous 14-day periods. In the last 14 days, the number of infections has decreased by 10,713 infections per day and average deaths per day has decreased by 87 deaths per day.

As of 8/28/20 we have had 185,901 deaths and 6,096,235 SARS-CoV-2 infections in the United States. Our new projections for the United States are that by October 4, 2020, we will have had 222,383 total deaths and 7,719,943 infections. We also project that by November 4, 2020, we will have had 252,949 total deaths and 9,101,347 total infections.