What is it?
The 2020-2021 coronavirus epidemic exploded in the United States after the emergence of a coronavirus transmitted from animals to humans. The coronavirus responsible for this epidemic has several names. The most commonly used name in my library is Severe Acute Respiratory Syndrome coronavirus 2, which is abbreviated SARS-CoV-2.
SARS-CoV-2 is an RNA virus, which means it stores genetic information as RNA. This contrasts with humans, who store genetic information (mainly) in the form of DNA. (Influenza virus is also an RNA virus.)
In order to replicate, SARS-CoV-2 must copy its RNA. This is accomplished by an enzyme called RNA-dependent RNA polymerase. RNA-dependent RNA polymerase is mistake prone, so RNA viruses have high mutation rates. (Some references suggest RNA viruses mutate one million times as fast as DNA viruses).
Coronavirus vaccines may have to be changed as new strains appear, but it is possible that vaccines aimed at the “spike protein” on coronavirus may be effective against most emerging strains.
What are the risks of coronavirus infections?
Death: As of 1/7/2021 California has reported 2,568,641 cases of Covid-19, the infection caused by SARS-CoV-2. These infections led to 28,538 deaths for a death rate of 1.1% in California. In comparison, the death rate from influenza is about 0.1% and the annual number of deaths from influenza is around 7,000 in California. Influenza is seasonal with the annual influenza epidemic starting in November and ending in April. The coronavirus epidemic did not stop in the summer months and the death rate from Covid-19 is 11 times as high as the death rate from influenza.
Prolonged symptoms:
· JAMA July 9, 2020 324(6):603-605: Among patients who were admitted to the ICU for Covid-19, then recovered and were discharged, 87.4% had 1 or more symptoms 60-days after discharge. The most common symptoms were fatigue and dyspnea.
At the other end of the spectrum:
· An outbreak on an aircraft carrier is described in NEJM 383;25 Dec 17, 2020 p 2417. 26.6% of the crew (1271 sailors, mean age 27) tested positive, of whom 55% had no symptoms at any time in their infection. 1.7% of infected sailors became sick enough to hospitalize and 0.3% required ICU care.
A population more representative of hospitalized patients is described in NEJM 383;25 Dec 17, 2020 p2417.
· This article describes outcomes in 1099 hospitalized patients infected w SARS-CoV-2. In this series 55 patients (5%) required admission to the ICU, 25 (2.3%) required intubation and 15 (1.4%) died.
Among the general population, according to JAMA Aug 25, 2020 Vol 324, No 8 p783:
· Between 15 and 20% of patients infected will require admission to a hospital. Most of these patients have other diseases, such as hypertension, diabetes, obesity, heart, lung, kidney or liver disease.
· 17-35% of hospitalized patients will require ICU care.
· 29-91% of ICU patients with COVID-19 will require intubation and ventilator support.
· About 25% of ICU patients with COVID-19 die of infection.
How do cancer and coronavirus interact?
This subject was reviewed in JAMA Sept 22, 2020 vol 324, no 12 p1141.
· Cancer diagnosis within 1-year of diagnosis w Covid-19 raises the risk of death from Covid-19.
· A more distant history of cancer (1 or more years prior to Covid-19) may not raise the risk posed by coronavirus.
· Metastatic and progressive cancer, male gender, increasing age, history of smoking, decreased performance status, active cancer treatment were associated with an increased risk of death. Up to 28% of patients with cancer at the time of Covid-19 may die of the infection.
· Coronavirus infections lead to delays in cancer treatments, raising the risk of cancer death.
Are coronavirus infections preventable?
· One of the major tragedies of the epidemic in the United States is that traditional infection control measures are fairly effective at preventing infection.
· PCR Oncology cut our patient encounters 20% in March-April of 2020, then returned to full schedules. Like other essential workers, we had to return to full schedules to meet the needs of our cancer patients. We used
o a combination of 2-3 layered cloth masks, N95 masks and KN95 masks,
o Ventilation (windows open whenever it was warm enough to crack a window and an exhaust fan turned on whenever possible)
o Hand washing (at least twice per patient encounter) and
o Disinfectant (all touched surfaces were disinfected with either a commercial wipe or 70% ethanol after every patient encounter).
o HEPA filters in every room are turned on when it is too cold to open windows.
§ With the above precautions none of us were infected as of 1/9/2021.
§ We have remained free of infection in spite of seeing an average of 155 patients per week, often accompanied by family.
§ These patients have visited during peak months of the pandemic, probably exposing us to coronavirus patients weekly
§ We have remained free of infection even though several of our family members became infected through their jobs or friends.
· I go to work every day wondering if this is the day I’ll get infected and knowing I’m likely to be exposed. So far, nearly 1-year into the epidemic, the above infection control measures have protected all PCR Oncology staff
· A fact of life in our society is that we have not had the leadership and/or will to control this epidemic with traditional infection control measures.
· The alternative to the above measures is vaccination.
How do the Pfizer and Moderna vaccines work?
The traditional viral vaccines use inactivated virus (virus that has been killed and cannot make us sick) or attenuated virus (virus that has been weakened, but not killed). These inactivated or attenuated viruses are injected (usually into the deltoid muscle), triggering an immune response that offers some degree of protection against severe infection. The effectiveness varies; influenza vaccine affords about 60% protection from infection. In contrast to traditional viral vaccines, the Pfizer and Moderna coronavirus vaccines are RNA-based, containing mRNA encoding one of the coronavirus genes.
In the normal course of our lives, DNA is “transcribed” to produce messenger RNA (mRNA), which is “translated” to make proteins.
The coronavirus contains about 30,000 nucleotides encoding 12 proteins, one of which is the 1273 amino-acid Spike protein. These vaccines utilize mRNA encoding the spike protein (but none of the other viral proteins). The mRNA has been modified to stabilize the spike protein and then processed so it is contained in tiny drops of lipid (fat). The vaccine consists of drops of fat containing mRNA encoding spike protein.
After vaccine is injected into human deltoid muscle (upper, outer arm), the fat in the vaccine merges with fat in cell membranes (just like drops of oil in your salad dressing merge a few minutes after you stop shaking the vinegar/oil). This delivers mRNA into cells, after which the normal machinery of the cell takes over and translates mRNA into spike protein.
Some spike protein is shed from cells into the blood stream while other bits of spike protein are “expressed” on the outside of cells. In both cases an immune response follows.
Since the vaccine contains mRNA for only about 15% of the virus, it cannot cause infection.
How effective are the Pfizer and Moderna coronavirus vaccines?
(FDA Healthcare provider fact sheet) The Pfizer vaccine was tested in 34,922 patients. 17,411 people received active vaccine and 17,511 received placebo. Eight people in the vaccine group suffered infections after the second (booster) shot compared with 162 people in the placebo group (95% reduction in risk of infection in vaccine group). The Pfizer product is given twice, 21 days apart.
The CDC reports 94.1% effectiveness for the Moderna vaccine, essentially identical to the Pfizer product. The Moderna vaccine is given twice, 28 days apart.
Phase I trials of both vaccines are described in NEJM Vol 383 No 25 Dec 17, 2020. Both vaccines appear to provide good protection from infection about 2-weeks after the booster shot.
Are these vaccines safe?
Short term risks:
The short-term safety data is both extensive and favorable. Risks include fever, muscle aches, chills, fatigue, headache, joint pains, nausea, pain and redness at the inject site. These side effects are somewhat more common with the Moderna vaccine (NEJM Dec 17 2020 vol 383 No 25 pages 2427 and 2439) than the Pfizer vaccine and typically pass in a few days.
Long-term risks:
There is no long-term safety data on these vaccines as of this writing (Jan 9, 2021) and neither I, the pharmaceutical companies nor the FDA are making any claim of long-term safety. As I have analyzed the risks, several thoughts come to mind:
· Coronavirus infection exposes us to 30,000 nucleotides of RNA and 12 viral proteins. The vaccine exposes us to about 4000 nucleotides of mRNA and 1 viral protein. It seems logical to believe that the long-term risk of the vaccine would be less than the long-term risk of infection.
· I have not seen any reports of death from the Moderna or Pfizer vaccines, whereas the risk of death from infection is 1.1%.
Having reviewed the above facts, most of the staff at PCR Oncology have opted to be vaccinated when offered.
When can I get vaccinated?
In short, I don’t know. The federal government has delegated responsibility to the states. The state of California is currently using Public Health departments, hospitals and some pharmacies (CVS and Walgreens) to administer coronavirus vaccines.
California has divided our vaccine program into phases.
Phase I: Mainly health care workers and nursing home residents.
Phase II: People above age 75, educators, child care, emergency services, food and agriculture workers. Phase II will begin “when vaccine supplies increase”. In one press briefing Governor Newsome mused that Phase II might begin in January 2021.
Phase III: General public.
The San Luis Obispo Public Health web-site has updates on many topics pertinent to the coronavirus epidemic. I expect them to post a “brief” on vaccinations when Phases II and III begin.
David Palchak MD