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 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 fourth time in a 14-day period. There were 133 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 11,210 infections per day. This increase in infections over the last four 14-day periods is 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 and the Brazilian isolates. 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 over Easter and Spring break as well as upgoing Memorial Day weekend, summer vacations and the July 4th holiday will all cause further increases. Vaccinations, increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 80 of plan) will be necessary to stop spread of mutants and cause  reductions in infections, hospitalizations and deaths in the future. On 4/09/21, 85,638 new infections occurred in the United States. There were also 929 deaths. The number of hospitalized patients is increasing, and only 9,078  patients are critically ill. The number of critically ill patients has increased by 468 in the last 14 days, while 13,006 new deaths occurred. The number of critically ill patients is increasing and a large number of patients are still dying each day. 

As of 4/09/21, we have had 574,840 deaths and 31,802,772 SARS-CoV-2 infections in the United States. We have had 949,742 new infections in the last 14 days. We are adding 474,871 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 4/9/21, twenty-one states had greater than 500,000 total infections, and 32 states had greater than 5,000 total 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 4/09/21, in the United States, 9.60% of the population has had a documented SARS-CoV-2 infection. In the last 5 months nearly 6% of our country became infected with SARS-CoV-2. 

As of 4/09/21, California was ranked 33rd in infection percentage at 9.34%. In North Dakota 13.71% of the population was infected (ranked #1) and in South Dakota 13.50% of the population was infected (ranked #2). Thirty-five states have greater than 9% of their population infected and 45 states have greater than 6% infected. Only one state has less than 3% of their population infected: Hawaii (2.15%). 

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 3,170 reported cases in the USA as of 3/11/21. As of 3/25/21 there are 8,337 reported cases in the USA. This isolate has now been found in 50 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. 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. 

As of 3/11/21 B.1.351, also known as the South African isolate, had 108 reported cases and has occurred in 23 states and the District of Columbia. As of 3/25/21 there are 266 reported cases in 29 states and the District of Columbia. On 3/11/21 the P.1 isolate (Brazil) had 17 reported cases and has been found in 10 states. As of 3/25/21 there were 79 P1 isolates in 11 states. (This data is available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html)

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), 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 3,618,594 infections and 55,455 total deaths. California is averaging 249 deaths per day in the last 14 days. Currently, 9.15% of the population in California is infected. Nationally, we rank 29th 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 Mutants Arrive in California

Stanford University announced this week that they have identified five infections with the Maharashtra India VOC 32421 (yet to be named) in the San Francisco Bay Area. Two additional isolates are PCR positive and pending sequencing. This isolate is a double-mutant responsible for up to 40% of the infections in India. 

Many readers 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 VOC from India apart from the other variants is that it has a different point mutation at 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 32421 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. 

In India on 4/9/21, 144,829 new infections and 773 deaths occurred. India now has the third-highest number of infections in the world (13,202,783) and the fourth-highest number of deaths (168,467). India has a population of 1,390,456,911. At the present time, only 0.94% of the country has been infected with SARS-CoV-2. International travel and trade will continue to spread this highly infectious isolate to other parts of the world. This infection has now landed in California, our most-populous state. 

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. 

LocationTotal Infections as of 4/9/21New Infections on 4/9/21Total DeathsNew Deaths on 4/9/21% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World135,290,124786,147*2,927,75013,3171.73%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 32421Maharashtra India VOC 32421NoNo
USA31,802,772
(ranked #1)
85,638
(ranked #3)
574,840
(ranked #1)
9299.56%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)Maharashtra India VOC 32421NoNo
Brazil13,375,414(ranked #2)   89,090(ranked #2) 348,934(ranked #2)3,6476.25%B2 lineageB.1.1.7 (UK)B.1.351 (SA)P.1 (Brazil)P.2 (Brazil)NoNo
India13,202,783(ranked #3)144,829(ranked #1)168,467(ranked #4)7730.94%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 32421Maharashtra India VOC 32421NoNo
United Kingdom4,365,456(ranked #6)3,145127,040606.40%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
California, USA3,694,147(ranked #9)3,60960,2821539.34%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)**P.2 (Brazil)Maharashtra India VOC 32421NoNo
Mexico2,267,109(ranked #14)5,140206,146(ranked #3)5481.74%B2 lineageB.1.1.7 (UK)B.1.429 + B.1.427 (USA)**P.1 (Brazil)NoNo
South Africa1,556,242(ranked #20)1,26753,226532.50%B2 lineageB.1.1.7 (UK)B.1.351 (SA)NoNo
Canada1,045,278(ranked #23)9,25523,251402.59%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.429 + B.1.427 (USA)**P.1 (Brazil)Yes, except Alberta ProvinceNo
Poland2,528,042(ranked #11)28,52328,5237686.40%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)NoNo
Turkey3,745,657(ranked #7)55,79133,45425314.40%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

*This number is higher than it was 2 weeks ago. It was 630,055. 

**Also referred to as CAL.20C

SARS-CoV-2 and Children

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 March 29, CDC reported 3,185 cases of MIS-C that meet the case definition and 33 deaths—that’s 568 new cases and 3 new deaths since the March 1 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 additional 1,000 cases, and only two months to add additional 1,185 cases. This suggests to us that B.1.1.7 is causing more MIS-C. 

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 April 1 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 April 1, A total of 284 child deaths due to COVID-19 were reported in 43 states (an increase of 16 child deaths since March 18). 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 49 (+2) child deaths. Arizona reported 26 (+2), California 16 (+1), Colorado 12, Georgia 10, Illinois 17 (+1) , Maryland 10, Tennessee 11, and New York City 22 (+1). 

The United Kingdom tracks hospitalizations by age group, and with the increased incidence of B.1.1.7 saw the number of child hospitalizations double from November 2020 to January 2021. This data likely influenced the decision to close school buildings and go into total lockdown there on January 4, 2021. 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 just on Day 80 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. We have been averaging 3 million vaccinations a day for the last seven days after having opened mass vaccination sites in multiple cities and states. To date, 178,837,781 doses of vaccine have been administered. As of 4/9/21, in the U.S., 68,202,458 people are fully vaccinated, which accounts for 20.5% of the population. On April 16, all people in the U.S. over the age of 16 will be eligible to receive a vaccine. The Biden administration is on track to exceed its goal of administering 200 million doses of vaccine in the first 100 days of the administration. Pfizer and Moderna have applied for emergency use authorization to administer their mRNA vaccines to children aged 12-16. Testing is ongoing for children in younger age groups. 

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 with vaccination should keep the pandemic from overwhelming our health care delivery system. 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 several states (including Texas, Florida, Iowa, Mississippi) open up everything and do away with masking and social distancing. We are seeing an increase of 11,000 new infections per day in the United States, compared to an increase of only 9 new infections per day two weeks ago. In the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This and other mutants may be doing 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 should also be available in the second 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. 

I still feel the current approach of companies and governments of making new vaccines against just the South African variant is wrong. In Brazil, where the P.1 isolate is dominant, they’ve had 1,050,649 infections and 45,208 deaths in the last 14 days. In South Africa, the total number of infections ever is 1,556,242, and they’ve had 53,226 deaths. Brazil is on track to have more infections and deaths in the next month than South Africa has had for the entire pandemic. It makes no sense to make a vaccine based on the South African mutant and not make one for the Brazilian P.1 mutant. 

The ideal approach to these 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 each 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 so far, the highest number of tests per day has been 1,709,210, so we’re doing nearly 600,000 fewer tests per day. 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. 

What We’re Reading This Week

COVID-19

SARS-CoV-2 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 third time in a 14-day period. There were 4,478 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has increased by 9 infections per day. This increase in infections over the last four 14-day periods may be secondary to SARS CoV-2 mutants B.1.1.7 (UK isolate), a New York isolate B.1.526, the CAL.20C isolate, the South African isolate and the Brazilian isolate. Increased mask usage and social distancing, which are a part of the Biden 100-day SARS-CoV-2 plan (day 66 of plan) will be necessary to stop spread of these mutants and cause further reductions in infections, hospitalizations and deaths. On 3/26/21, 76,976 new infections occurred in the United States. There were also 1,289 deaths. The number of hospitalized patients is decreasing, and only 8,610 patients are critically ill. The number of critically ill patients has decreased by 3,060 in the last 14 days, while 14,837 new deaths occurred. This still suggests that the number of critically ill patients is decreasing because a large number of patients are still dying each day. 

As of 3/26/21, we have had 561,142 deaths and 30,853,032 SARS-CoV-2 infections in the United States. We have had 792,803 new infections in the last 14 days. We are adding 396,402 infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 3/12/21, twenty states have had greater than 500,000 total infections, and 30 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 3/12/21, in the United States 9.28% of the population has had a documented SARS-CoV-2 infection. In the last 4 months nearly 6% of our country became infected with SARS-CoV-2. 

As of 3/26/21, California was ranked 31st in infection percentage at 9.25%. In North Dakota 13.43% of the population was infected (ranked #1) and in South Dakota 13.20% of the population was infected (ranked #2). Thirty-four states have greater than 9% of their population infected and 45 states have greater than 6% infected. Only two states have less than 3% of their population infected: Vermont (2.96%), and Hawaii (2.06%). 

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 3,170 reported cases in the USA as of 3/11/21. As of 3/25/21 there are 8,337 reported cases in the USA. This isolate has now been found in 50 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. 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. 

As of 3/11/21 B.1.351, also known as the South African isolate, had 108 reported cases and has occurred in 23 states and the District of Columbia. As of 3/25/21 there are 266 reported cases in 29 states and the District of Columbia. On 3/11/21 the P.1 isolate (Brazil) had 17 reported cases and has been found in 10 states. As of 3/25/21 there were 79 P1 isolates in 11 states. (This data is available at https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html)

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), 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 3,618,594 infections and 55,455 total deaths. California is averaging 249 deaths per day in the last 14 days. Currently, 9.15% of the population in California is infected. Nationally, we rank 29th 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. 

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. 

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 March 1, CDC reported 2,617 cases of MIS-C that meet the case definition and 33 deaths. (As of March 26, 2021, the CDC has not updated its MIS-C data from the March 1 data. We’re sure why the CDC would wait a whole month to update this data.) 

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 AAP’s March 18 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 March 18, A total of 268 child deaths due to COVID-19 were reported in 43 states (an increase of 15 child deaths since March 4). 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 47 (+3) child deaths. Arizona reported 24, California 15 (+1), Georgia 10, Illinois 16, Maryland 10, Pennsylvania 9 (+2), New Jersey 6 (+2) and New York City 21. 

The United Kingdom tracks hospitalizations by age group, and with the increased incidence of B.1.1.7 saw the number of child hospitalizations double from November 2020 to January 2021. This data likely influenced the decision to close school buildings and go into total lockdown there on January 4, 2021. 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 just on Day 66 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. We have been averaging 2.6 million vaccinations a day for the last seven days after having opened mass vaccination sites in multiple cities and states. To date, 138 million doses of vaccine have been administered. The new goal of the Biden administration is to administer 200 million doses of vaccine in the first 100 days of his administration. 

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 like B.1.429 + B.1.427 (Cal.20C), the UK, Brazillian and South African variants will probably spread rapidly throughout the United States over the next 90 days as several states (including Texas, Florida, Iowa, Mississippi) open up everything and do away with masking and social distancing. We are starting to see increased numbers of infections occurring in the United States. In the last seven days, we’ve averaged 4,377 infections per day greater than the preceding seven days. In the UK, B.1.1.7, has increased the number of infections, hospitalizations and deaths. This mutant may be doing 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 should also be available in the second 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. 

I still feel the current approach of companies and governments of making new vaccines against just the South African variant is wrong. In Brazil, where the P.1 isolate is dominant, they’ve had 1,039,036 infections and 32,046 deaths in the last 14 days. In South Africa, the total number of infections ever is 1,543,079, and they’ve had 56,602 deaths. Brazil is on track to have more infections and deaths in two weeks than South Africa has had for the entire pandemic. It makes no sense to make a vaccine based on the South African mutant and not make one for the Brazilian P.1 mutant. 

The ideal approach to these spreading major mutations on at least four 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 each 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 so far, the highest number of tests per day has been 1,709,210, so we’re doing nearly 600,000 fewer tests per day. 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

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.

PubMed, Support Group

[August] Articles of Interest

Dr. Wright discussed the following articles with the members of the Borrelia (Tick-borne Relapsing Fever and Lyme disease) patient support group in their August meeting:

1. Humans Infected with Relapsing Fever Spirochete Borrelia miyamotoi, Russia (link) (PDF)

Dr. Wright drew attention to two figures from this article.

Figure 2

Examples of relapsing fever episodes in 2 patients with Borrelia miyamotoi infection.

Interesting Points:

  • This figure illustrates that an antibody test can be negative at anywhere between 15 and 37 days post-tick bite, even though a PCR may be positive. Each graph above represents episodes of relapsing fever in one patient from the study.
  • During the time that both patients were hospitalized with high-spiking fevers, antibody tests for Borrelia miyamotoi were negative.
  • Antibiotic therapy was not initiated until 30 days after the tick bite. If the patients had been infected with Rocky Mountain spotted fever instead of Borrelia miyamotoi, some would likely have died waiting to get treatment.
  • In cases where doctors are not sure which tick-borne infection a patient has–because symptoms of fever and myalgia come with many infections–it is important to start antibiotic treatment right away.
  • Dr. Wright reminded the group that, according to Israeli studies on Borrelia persica, prophylaxis does not work at 72 or 96 hours. If treating a patient with antibiotics later than 48 hours after a tick bite, doxycycline should be given for at least two weeks.

Figure 3 (Click image to enlarge)

Phylogenetic tree of Borrelia spp. detected in persons and ticks, based on flagellin gene fragment (A) and16S rRNA gene fragment (B).
Phylogenetic tree of Borrelia spp. detected in persons and ticks, based on flagellin gene fragment (A) and16S rRNA gene fragment (B). Sequences were aligned and analyzed by using MEGA4.1 software (www.megasoftware.net). Genetic trees were constructed from the partial nucleotide sequences of the flagellin gene and the 16S rRNA gene by using the Kimura 2-parameter model and the unweighted pair group method with arithmetic mean. Arrow indicates the 16 Borrelia spp. from Yekaterinburg in 2009 that had the same nucleotide sequence. Circles indicate sequences that we listed in GenBank (accession nos. GU797331–GU797346 and JF951378–JF951392). Sequences for B. burgdorferi sensu lato and relapsing fever borreliae are shown for comparison. Scale bars indicate genetic distance.

Interesting Points:

  • There appear to be three main types of Borrelia miyamotoi: 1) Russian/Asian, 2) European, and 3) U.S. and Japanese.
  • It’s possible that we have an undiagnosed Borrelia miyamotoi epidemic. It’s already been detected in wild turkeys in the U.S. If we had commercially-available tests for it, we’d likely be detecting it in people, too.
  • People who test positive for Borrelia hermsii with a low antibody titer could have Borrelia miyamotoi.
  • Researchers say that species like Borrelia hermsii that cause Tick-borne Relapsing Fever are only carried by soft-bodied ticks, but Borrelia miyamotoi is carried in two different U.S. species of hard-bodied ticks. If there is one exception, there are likely others.

2. Signs and significance of a tick-bite: psychiatric disorders associated with Lyme disease (link to abstract)

This is a study from the Netherlands in which a researcher reviewed the literature on psychiatric disorders and Lyme disease. The disorders most often associated with Lyme disease were:

  • depressive disorders
  • psychotic disorders
  • cognitive impairment
  • memory and concentration disorders

Dr. Wright mentioned a case of a child with “atypical psychosis” who turned out to have a Borrelia hermsii infection, and recommended that patients with psychiatric disorders of an unknown origin be screened for Borrelia infections.

3. Bell palsy in Lyme disease-endemic regions of Canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease. (link to abstract)

  • About 25% of cases of Bell palsy in Canada are due to Lyme disease.
  • A facial palsy is a neurologic presentation of the infection, which means doctors missed the infection in its acute stage. For this reason, Dr. Wright believes it is more effective to treat patients with Bell palsy with IV ceftriaxone (as opposed to oral doxycycline).
  • In this study, researchers only looked for one isolate of Borrelia burgdorferi. It’s possible that if they had looked for multiple isolates, greater than 25% of Bell palsy cases would have been due to Borrelia infections.

4. Aseptic meningitis and adult respiratory distress syndrome caused by Borrelia persica. (link to abstract)

  • Borrelia persica is a relapsing fever species commonly found in the middle east and has been studied extensively by Israeli scientists.
  • In this study, they find that adult respiratory distress syndrome (ARDS) can be a complication of Borrelia persica infection.
  • ARDS is a known complication of Borrelia hermsii infection as well.
  • When a patient has ARDS, fluid accumulates in the lungs, and the patient has to be put on a ventilator. Dr. Wright suggests that perhaps we should be screening patients on ventilators for Borrelia infections.

5. Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin. (link to abstract)

  • Clarithromycin and amoxicillin differ from ceftriaxone and doxycycline in that they cannot cross the blood-brain barrier. In advanced infections with neurological symptoms, it is important to be treated with an antibiotic that can cross this barrier.
  • To date, Dr. Wright knows of no study of prophylaxis in children; this would be helpful to have.

Disease prevention reminders:

Dr. Wright discourages patients from letting their pets sleep with them in their beds, as this is how many zoonotic infections can be spread. He also stresses the importance of keeping one’s house free of rodents (which carry ticks). “We still haven’t learned the Middle Ages lesson about rodents living with humans,” Dr. Wright said in reference to the bubonic plague.