Tag: positivity

COVID-19

SARS-CoV-2 Update

davidcwrightmd

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 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 28 fewer deaths per day than in the last 14-day period. In the last 14 days, the number of infections has decreased by 17,700 infections per day.  Our infections per day is still extremely 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 and the Brazilian isolates and the new Indian isolate. 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 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 SARS-CoV-2 plan (day 108 of plan) will be necessary to stop spread of mutants and cause  further reductions in infections, hospitalizations and deaths in the future. On 5/07/21, 49,491 new infections occurred in the United States. There were also 770 deaths. The number of hospitalized patients is decreasing, but 9,140  patients are still seriously or critically ill. The number of critically ill patients has decreased by 692 in the last 14 days, while 9,836 new deaths occurred. The number of critically ill patients is decreasing for the second 14 day period but a large number of patients are still dying each day. 

As of 5/07/21, we have had 594,911 deaths and 33,418,826 SARS-CoV-2 infections in the United States. We have had 683,122 new infections in the last 14 days. We are adding an average of 341,561 infections every 7 days. Each million infections usually results in 10,000 to 20,000 deaths. On 5/07/21, twenty-two states have had greater than 500,000 total infections, and 32 states have had greater than 5,000 total deaths. Eight states (Geogia, 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 5/07/21, in the United States, 10.04% 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 5/07/21, California was still ranked 35th in infection percentage at 9.50%. In North Dakota 14.21% of the population was infected (ranked #1), while Rhode Island was at 14.11% (ranked #2) and South Dakota was at 13.93% of the population infected (ranked #3). Thirty states have greater than 10% of their population infected. Only one state has less than 3.5% of their population infected: Hawaii (2.30%). Fourteen states still have greater than 1,000 new infections per day with Florida leading again on 5/7/21 with 4,175 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 85,324 cases of B.1.1.7 identified in the US to date. (See chart below.)

At 197 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 1,161 isolations. 

And the United States has now surpassed Brazil for the most isolations of P.1 in the world, with 5,355 overall and 1,955 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 334 total cases, 197 of which were identified in the last four weeks. This also means that we had 137 known cases of this variant in the US more than a month ago, despite the fact that American news media and the CDC have only recently begun educating the public about this variant. 

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 3,756,393 infections and 62,220 total deaths. California is averaging 58 deaths per day in the last 14 days, which is a 22 deaths per day decrease from the preceding 14 day period. Currently, 9.50% 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 three 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. Two additional isolates were PCR positive and pending sequencing. This isolate is a double-mutant responsible for greater than 40% of the infections in India.  In the last 14 day update India had had 2,080,793 new infections in the  7 days prior which was a 58% change in the number of infections from the preceding 7 days (1,318,900 infections). Indian had reported the three highest numbers of new infections per day at 349,165 on 3/24/21, 345,147 on 2/23/21, and 332,503 new infections on 4/22/21. India is the only country to report over a million infections in three days. The previous one day record was 302,000 infections in the United States. In India 13,876 new SARS-CoV-2 deaths had occurred in the last seven days compared to 7,206 deaths in  the preceding seven days. This was a 93% increase in the death rate in the last seven days. 

The data from India the last 14 days ending on 5/07/21 is even more disturbing. India has had 5,284,155 infections in the last 14 days with an average of 377,440 infections per day or 1,132,320 infections every three days. During this 14 day period India reported 48,716 deaths or 3,480 deaths per day. On May 7, 2021 India reported 401,326 new infections and 4,194 new deaths. On 5/7/21 the total deaths due to SARS-CoV-2 infections in India now stands at 238,265. India with a population of 1,390,456,911 has had only 1.57% of the country infected. Their hospitals are still running out of oxygen, medications, beds and ventilators. They had only been able to vaccinate approximately 140 million people.Sadly a health disaster is now occurring 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 little 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 B1.617 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 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.

LocationTotal Infections as of 5/07/21New Infections on 5/7/21Total DeathsNew Deaths on 5/07/21% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask Mandate?Currently in Lockdown?
World157,526,509836,0313,283,26013,7412.02%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 B.1.617 BV-1 (Texas, USA)NoNo
USA33,418,826
(ranked #1)		49,491
(ranked #3)		594,911
(ranked #1)		79010.04%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 B.1.617BV-1 (Texas, USA)NoNo
Brazil15,078,360(ranked #3)   78,377(ranked #2) 401,326(ranked #2)2,2177.05%B2 lineageB.1.1.7 (UK)B.1.351 (SA)P.1 (Brazil)P.2 (Brazil)NoNo
India21,886,612(ranked #2)401,326(ranked #1)238,265(ranked #3)4,1941.57%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 B.1.617NoNo
United Kingdom4,431,043(ranked #7)2,490127,598156.49%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)Maharashtra India VOC B.1.617NoNo
California, USA3,756,393(ranked #9 in world)2,16662,220489.50%B2 lineageB.1.1.7 (UK)B.1.351 (SA)B.1.429 + B.1.427 (USA)*P.2 (Brazil)Maharashtra India VOC 32421NoNo
Mexico2,358,831(ranked #15)2,846218,173(ranked #4)1661.81%B2 lineageB.1.1.7 (UK)B.1.429 + B.1.427 (USA)*P.1 (Brazil)NoNo
South Africa1,592,326(ranked #20)1,95654,687672.65%B2 lineageB.1.1.7 (UK)B.1.351 (SA)NoNo
Canada1,273,169(ranked #22)7,84924,529403.54%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
Poland2,824,431(ranked #13)6,05369,4451667.46%B2 lineageB.1.1.7 (UK)B.1.525 (Nigeria/UK)B.1.351 (SA)NoNo
Turkey4,998,089(ranked #5)20,10742,4652785.87%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
*Also referred to as CAL.20C

The Road Ahead

We are on Day 108 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. As of 5/7/21, 149.5 million people have had one dose of any vaccine. 8.6 million have had a single-dose vaccine (J&J). 108.9 million people are fully vaccinated. Therefore, 32 million people still need a second dose of either the Pfizer or the Moderna vaccine. 

As of April 16, all people in the U.S. over the age of 16 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. Pfizer and Moderna have applied for emergency use authorization to administer their mRNA vaccines to children aged 12-15, and the FDA is expected to authorize the Pfizer vaccine for this age group next week. Testing is ongoing for children in younger age groups and may be approved for ages 2-11 by 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 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 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 second or third 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 another 849,250 infections and 32,770 deaths in just the last 14 days. In the last 42 days in Brazil 2,762,595 infections have occurred and 115,667 deaths. In South Africa, the total number of infections during the pandemic is 1,592,326 and a total of 54,687 deaths. Brazil had more infections and deaths in one month than South Africa has had for the entire pandemic. It makes no sense to make a vaccine based on just the South African mutant and not make one for the Brazilian P.1 mutant. Even worse is the current situation with the Indian SARS-CoV-2 VOC B.1.617. In the last 14 days India has had 5,284,155 new infections and 48,716 deaths. If India shuts down, among other things the generic drug industry could fail.

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 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 1,260,357 tests per day (7-day moving average); that’s 747,962 fewer tests 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 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. 

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