a Covid news digest
for the period November 21 – December 11, 2020 FINAL EDITION
FRONT PAGE
- Vaccines – how effective are they and how often do they need to be repeated? There are four front-runners in the race to government approval. CovidGram takes an in-depth look at the two vaccines that use mRNA technology. As of December 11, Pfizer-BioNTech’s mRNA vaccine has received approval in Britain, but not yet in the U.S. Many key U.S. researchers consider the British approval too hasty. The quick answer on how long the vaccines will provide immunity and how often they will need to be repeated is “No one knows.” Carl Zimmer at the New York Times answered, “We don’t know. Both Moderna and Pfizer started their trials on July 27, so they have been able to follow their volunteers for only a few months so far. It’s conceivable that the vaccines provide long-lasting protection or fade away in under a year and require a booster.”
- What are the long-term effects of Covid? Although the extent of patients with long-term Covid is not yet known precisely, the problem is widespread enough that Anthony Fauci last week labeled it a significant public health issue, and clinics specializing in long-term Covid are starting to appear in medical centers.
- Free testing. Reports of long delays in getting test results from Marion County Health Department. Consider getting tested for free at CVS Pharmacy or the Indiana State Department of Health A home test kit priced around $50 just received FDA approval and should be available soon. A $25 antibody test is available through some Kroger pharmacies.
FEATURE STORIES
I. Vaccine effectiveness
Immune system and vaccine basics
All vaccines operate on the principle that viruses, like all invasive agents (aka antigens), will trigger the immune system to manufacture specialized antibodies to destroy those specific viruses.
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This immune response can be a powerful weapon against infectious diseases, but when a new virus comes along like SARS-CoV-2—the virus that causes Covid—it takes time for the adaptive immune system to a) recognize the intruding virus and b) produce the custom-made antibodies that will neutralize the virus. That delayed response allows the virus to replicate widely enough to cause the high fever, breathing difficulty, heart damage, stroke, or death that Covid is known to produce. The two curves in the diagram below demonstrate how the production of antibodies lags behind the peak of the infection. [This diagram was made by Whitmire Medical, a producer of antibody tests.]
The gray curve indicates viral load in the body, and the red curve indicates the level of antibodies produced. The horizontal scale at the bottom indicates the number of days since exposure to the coronavirus starting at 5 days before the appearance of symptoms (symptoms appear at day 0 and viral exposure occurs at day -5 on this scale.)
According to this timeline then—which represents a typical progression of Covid disease—the adaptive immune system doesn’t start producing antibodies until 7 days after exposure. (To demonstrate the complexity of the body’s defenses, another weapon called the innate immune system, is battling the viral invasion from the first day of exposure, but without the help of antibodies. If this first line of defense gets overwhelmed, the virus has the chance to produce illness.)
So, a Covid infection will produce antibodies to prevent the next infection for a while, but with a possibly fatal disease like Covid, who wants to have an infection in the first place?
Shortcut to immunity. A successful coronavirus vaccine takes the delay out of the immune response. It convinces the body that a real infection is happening when in fact it is a mere shell of the virus or a small, harmless part of the real thing. The immune system recognizes the unique signature of coronavirus in that small part and produces the appropriate antibodies anyway.And voila! The body has gained immunity without the danger of an actual infection. A particularly good graphic illustration of the immune process is provided at the end of this CovidGram in an appendix.
Types of vaccines
Classic vaccines mimic a viral invasion by injecting killed or weakened virus particles into the body so that the immune system will manufacture antibodies for that particular virus (antigen). In the event that particular virus invades the body at some point in the future, antibodies will be present to provide immunity.
mRNA vaccines. Some of the new vaccines take an indirect route to introducing virus antigens into the body. Instead of injecting modified virus particles, these vaccines inject a biochemical that will allow the cells to produce coronavirus proteins which will then trigger the production of antibodies specific to that virus. In two of the new vaccines, manufactured by Pfizer-BioNTech and Moderna, that biochemical is mRNA.
mRNA is a type of chain-shaped molecules that contains the blueprint for making particular proteins. It is used by all our cells to produce the proteins needed for the complex function of our bodies. The particular mRNA made by Pfizer-BioNTech and Moderna obligates our cells to produce SARS-CoV-2 signature proteins that unmistakably identify as parts of the coronavirus—for example, the spike protein—and that will reliably induce the immune system to produce antibodies against the virus.
Now, mRNA is not just a biochemical; it is an entire biochemical manufacturing technology built over the last couple decades by pharmaceutical companies. These companies have figured out how to appropriate the means of production of living cells to manufacture proteins to order, vastly reducing the cost of synthesizing proteins in the laboratory or drug factories. Making viral mRNA in the laboratory and pharmaceutical plant is far cheaper than making virus proteins. mRNA represents a type of cellular farming in which our cells are the soil, mRNA is the seed, and specific proteins are the cash crop.
Other vaccine types. Another vaccine close to finishing effectiveness and safety trials is one made by the Oxford University-AstraZeneca team. This vaccine falls into a category called “viral vector” according to a widely recognized vaccine classification system. The Sputnik V vaccine currently approved for use in Russia is also a viral vector vaccine. Viral vector vaccines use another virus, for example measles, that has been genetically modified to contain the coronavirus spike gene. This virus, which has been weakened to prevent infection, then manufactures spike proteins which then cause the immune system to produce coronavirus antibodies.
Vaccine effectiveness
The following chart shows the effectiveness of the four front runners in the race to produce vaccines against Covid. The data in this chart is supplied by the vaccine manufacturers, but the scientific community is fairly confident in the reliability of these numbers.
What could possibly go wrong?
The world is currently at the beginning of the vaccine phase of this prolonged Covid ordeal. Absolutely no one in the scientific community or among the vaccine companies knows what the long-term side effects might be or how long immunity will last. The state of knowledge is that uncertain. All we know for now is that the mRNA vaccines can produce soreness at the injection site, muscle aches, fatigue, and a few other minor symptoms in the short term.
mRNA technology has been harnessed since the 1990s for various medical applications, but injecting viral mRNA as a vaccine for humans is relatively new. All our knowledge about the way mRNA works in cells inclines the scientific community to believe that there will be no serious long-term side effects. But, like many medical innovations throughout history, Covid vaccines are an experiment, we are the subjects, and we need to choose our level of risk based on the best available evidence.
References
JAMA Network, April 28, 2015, The immune system
https://jamanetwork.com/journals/jama/fullarticle/2279715
New York Times, October 5, 2020, Charting a Covid-19 immune response
https://www.nytimes.com/interactive/2020/10/05/science/charting-a-covid-immune-response.html
Vaccines, November 16, 2020, Antibody responses to SARS-CoV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712576/
MedPage Today, December 3, 2020, Want to know more about mRNA?
https://www.medpagetoday.com/infectiousdisease/covid19/89998
Nature, April 28, 2020, The race for coronavirus vaccines
https://www.nature.com/articles/d41586-020-01221-y
Youtube, Covid-19 animation
https://www.youtube.com/watch?v=5DGwOJXSxqg
STAT, December 4, 2020, How key decisions slowed FDA’s review of vaccines
CDC, July 31, 2020, Symptom duration and risk factors for delayed return to normal health
https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm
II. Long-term Covid effects
Covid arouses dread in the medical community for many reasons. 1) Even though we now have an approved vaccine, many more people are still going to be infected over at least the next several months. 2) Covid spreads commonly through people who show no symptoms. 3) Covid can kill even after some patients appear to recover from serious symptoms. 4) And not least among the concerns is the way Covid produces persistent health problems.
We don’t know how long these Covid effects will last, but a substantial portion of patients—estimates are in the millions worldwide—continue to feel these effects up to the present day, and the medical community faces many uncertainties about how to treat them.
A revealing personal account. A 33-year old female journalist shared her ongoing saga of long Covid in a revealing article at BuzzFeedNews. She describes the first couple of months after being infected sometime in April:
“For about a month, I was throwing up a lot and had to switch to a bland diet. Then for about two months, I woke up every day with intense chest pain, as if I’d been doing chest presses all night in my sleep. The headaches, fevers, and shortness of breath came and went throughout. Month to month I can see that I’m very slowly getting some energy back — but there’s the constant possibility, which no one has been able to really rule out, that one of these setbacks will be so bad that I actually do end up in the hospital, or worse.”
Official lists of long Covid symptoms. The CDC recently published the following list of possible long-term effects of Covid. A more detailed analysis of long haul Covid will appear in the next CovidGram.
“The most commonly reported long-term symptoms include:
- Fatigue
- Shortness of breath
- Cough
- Joint pain
- Chest pain
Other reported long-term symptoms include:
- Difficulty with thinking and concentration (sometimes referred to as “brain fog”)
- Depression
- Muscle pain
- Headache
- Intermittent fever
- Fast-beating or pounding heart (also known as heart palpitations)
More serious long-term complications appear to be less common but have been reported. These have been noted to affect different organ systems in the body. These include:
- Cardiovascular: inflammation of the heart muscle
- Respiratory: lung function abnormalities
- Renal: acute kidney injury
- Dermatologic: rash, hair loss
- Neurological: smell and taste problems, sleep issues, difficulty with concentration, memory problems
- Psychiatric: depression, anxiety, changes in mood
The long-term significance of these effects is not yet known. CDC will continue active investigation and provide updates as new data emerge, which can inform COVID-19 clinical care as well as the public health response to COVID-19.”
The World Health Organization reported the following list of long-term effects.
Body systems and organs that can be affected :
- Heart – Damage to heart muscle, heart failure
- Lungs – Damage to lung tissue and restrictive lung failure
- Brain and the nervous system – Loss of sense of smell (anosmia), consequences of thrombo-embolic events such as pulmonary embolism, heart attack, stroke, cognitive impairment (e.g. memory and concentration)
- Mental health – Anxiety, depression, post-traumatic stress disorder and sleep disturbance
- Musculoskeletal and others – Pain in join and muscles, fatigue
References
New York Times, December 5, 2020, Covid long-haulers need urgent attention
https://www.nytimes.com/2020/12/04/health/covid-long-term-symptoms.html
60 Minutes, November 24, 2020, Covid’s long haulers
https://www.youtube.com/watch?v=0gLmMPOHDwM&feature=youtu.be
Washington Post, December 9, 2020, Canadian woman’s Covid symptoms persist after 9 months
CDC, November 13, 2020, Long-term effects of Covid
https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html
III. Fatality rates and underlying health conditions
At the top of the list of underlying diseases among people who died of Covid in China in February was cardiovascular disease. Ten and a half percent of Covid fatalities in that data set had cardiovascular disease as a comorbidity.
However, a recent review of worldwide medical literature reported different results. That review reported hypertension, i.e. high blood pressure, as a pre-existing condition in an average of 46 percent of people who died from Covid. Diabetes was the next most frequent comorbidity at 26 percent, and cardiovascular disease averaged 21 percent as a comorbidity. The study also mentioned asthma in its ranking of comorbidities. An average of 3 percent of people who died from Covid had asthma as an underlying condition.
References
CDC, July 17, 2020, Characteristics of Covid fatalities
https://www.cdc.gov/mmwr/volumes/69/wr/mm6928e1.htm
CDC, December 9, 2020, Provisional death counts for Covid
https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
PLOS, October 23, 2020, Prevalence of underlying diseases: review article
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241265
Our World in Data, Case fatality rates and age, underlying conditions
https://ourworldindata.org/mortality-risk-covid#case-fatality-rate-of-covid-19-by-age
IV. Antibody testing
HealthLabs.com. Abott. According to independent studies from Abbott Labs, Quest Diagnostics and the University of Washington, this test has a sensitivity of 100% and a specificity of 99.6% making it the most accurate COVID-19 antibody test currently available. This test is FDA-authorized and is based on a newly released test system from Abbott and will be run on Abott’s ARCHITECT i1000SR and i2000SR laboratory instruments.
Kroger antibody test
https://www.kroger.com/health/pharmacy/covid-care
Whitmire Medical, Covid antibody test
https://www.whitmiremedical.com/covid-19-testing
CDC, November 25, 2020, Decline in antibodies after mild infection
https://www.cdc.gov/mmwr/volumes/69/wr/mm6947a2.htm
JAMA, November 24, 2020, Antibodies, immunity, and Covid-19
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2773575
FDA, November 6, 2020, FDA authorizes first antibody test for Covid
Science Translational Medicine, April 29, 2020, Orally bioavailable broad-spectrum antiviral
https://stm.sciencemag.org/content/12/541/eabb5883
HuffPost, October 29, 2020, Can Covid-19 damage your teeth and mouth?
https://www.huffpost.com/entry/covid-19-damage-teeth-mouth_l_5fb1d951c5b6d05e86e85b0a
Reuters, Covid map
Science Daily, December 3, 2020, Oral drug blocks Covid transmission
Science Daily, November 30, 2020, Mucosal immunity
V. Other news
NPR, November 26, 2020, Restricting small gatherings is not enough
Nature, Can dogs smell Covid?
Reuters, November 26, 2020, Victoria, Australia beats Covid after 100 days of lockdown.
IEEE Bulletin, November 26, 2020, Detecting Covid through sound
https://www.wbur.org/hereandnow/2020/11/27/coronavirus-sound-test
APPENDIX
The graphic below illustrates the entire immunity process in particularly helpful detail. It is reproduced from an article in the journal Nature. Artist: Nik Spencer.