Month: January 2021

COVID-19

SARS-CoV-2 (COVID-19) 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 our projections of future total infections and deaths since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

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

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

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

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

New Mutants

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

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

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

A California Mutant

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

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

Watching the Data

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

The Road Ahead

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

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

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

COVID-19

SARS-CoV-2 (COVID-19) Update

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 Worldometer aggregators data set to make our projections of future total infections and deaths since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

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

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

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

As of 1/15/21, we have had 401,856 deaths and 24,102,429 SARS CoV-2 infections in the United States.  We have had 3,473,834 new infections in the last 14 days. We are adding  over 1.7 million infections every 7 days. Each million infections usually results in at least 20,000 deaths. On 1/15/21, fifteen states have had greater than 500,000 total infections, and 26 states had greater than 5,000 total deaths. 

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

As of 1/15/21, in the United States 7.28% of the population has had a documented SARS-CoV-2 infection. California was ranked 26th in infection percentage at 7.40%. In North Dakota 12.54% of the population was infected (ranked #1) and in South Dakota 11.86% of the population was infected (ranked #2). Thirty-six states already have greater than 6% of their population infected (North Dakota, South Dakota, Iowa, Nebraska, Wisconsin, Utah, Montana, Illinois, Idaho, Tennessee, Rhode Island, Minnesota, Wyoming, Kansas, Indiana, Arkansas, Nevada, Alabama, Oklahoma, Mississippi, Arizona, New Mexico, Louisiana, Missouri, Georgia, Alaska, Florida, Texas, Connecticut, North Carolina, Colorado, Massachusetts, Ohio, New Jersey, Delaware and Kentucky). 

A new mutant SARS-CoV-2 virus (lineage B.1.1.7), first seen in the UK in September, has now been found in multiple other countries. In California, two patients in LA county and three patients in San Diego county are infected with this new mutant. Two patients in Colorado and one in Florida have also been identified as of 12/31/20. As of 1/15/21, this new mutant has been found in nine other states (New York, Georgia, Texas, Connecticut, Pennsylvania, Ohio, Utah, Maryland, and Wisconsin. This isolate (let’s call it Lineage B.1.1.7 or SARS-CoV-2 UK) is more infectious than other previously circulating B2 lineage isolates (probably 30 to 40% increased infectivity). There are two deletions and six other mutations in its spike protein. One mutation involves a change of one amino acid, an asparagine at position 501 in the receptor binding motif with a tyrosine. This enhances binding (affinity) to the ACE-2 receptor and may alone be responsible for the increased infectivity of this isolate. Due to air and other travel this isolate should become the dominant isolate worldwide.  

In a research letter pending publication in Clinical Infectious Diseases, a group of NHS doctors describe the case of a patient who was first infected with SARS-CoV-2 in April and became reinfected in December. After the patient’s second infection, Whole Genome Sequencing (WGS) was performed on samples from both instances of infection, and it was determined that the first infection in April was with a B.2 lineage variant and the second infection was with the new B.1.1.7 variant. While the patient, “a 78 year old man with a history of Type 2 Diabetes Mellitus, diabetic nephropathy on haemodialysis, chronic obstructive pulmonary disease (COPD), mixed central and obstructive sleep apnoea, ischaemic heart disease, with no history of immunosuppression” had only had a mild illness (fever being the only symptom) during the first infection, during the second infection, he had much more severe symptoms, including shortness of breath and hypoxia, which led to emergency intubation. He developed “Severe Covid-19 pneumonia complicated by mycocardial infarction with resulting trifascicular block and Atrio-Ventricular (AV) dissociation and pulmonary oedema.” (To read the full research letter, visit https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab014/6076528 and click PDF.)

The patient described in this research letter was not protected by a natural infection with a B2 lineage SARS-CoV-2 isolate in April 2020 from having a potentially lethal second infection with a B.1.1.7 lineage variant in December 2020, suggesting that folks who have had a past SARS-CoV-2 infection should not expect to have any immunity to new variants such as B.1.1.7. All of the currently available vaccines were developed with spike protein from B2 lineages, so it remains to be seen whether these vaccines will protect against B.1.1.7 infections or the additional isolates discussed below.

A second mutation in the loop sequence has been identified in the South African, Brazilian, and Japanese isolates this week. This mutation will also enhance binding to the ACE-2 receptor and may interfere with binding of monoclonal antibodies to the SARS-CoV-2 receptor binding motif. If this rate of mutations and deletions continues in the spike protein, especially in the receptor binding domain and motif, in my opinion, then vaccine reformulation will be required in 2021.

We have a new President-elect and Vice President-elect, now confirmed by the electoral college and approved in the House and Senate on 1/06/21 despite a riot and invasion of the Capital by President Trump’s supporters. The President-elect has made the pandemic a first priority after Inauguration on January 20, 2021. Testing, wearing masks, social distancing and washing our hands frequently should no longer be political issues. These are non-pharmaceutical interventions used by most successful countries and some states to protect their citizens and their economies. New Zealand, Taiwan, and Australia are three countries that have done this successfully.  In the United States, Maine, Vermont, and Hawaii are doing a better job handling the pandemic than many of our states. The pandemic problem is overwhelming our health care delivery system in many states. Unless things change before Inauguration Day on January 20, 2020 (5 days away) we could, by our predictions, have an additional 1,221,405 SARS-CoV-2 infections and another 15,815 deaths. Our infections per day and deaths per day will continue to increase for at least another 8 to 12 weeks.

The Pfizer and Moderna RNA vaccines are both now approved in the USA. To vaccinate 80% of our population with two doses of vaccine, we will need over 500 million doses of vaccine. Unless we start vaccine shipments to clinics and physicians’ offices, not just hospitals and pharmacies, I doubt most people will be able to receive any vaccine until April 2021.  

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