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.