This was a lecture I gave for the Upstate Nurse Practitioners Association. This is a comprehensive overview. I would to thank all health care professionals for doing their jobs as well as they can.

1. COVID-19:
A Primer on the
Diagnosis and Treatment
2020 Sept 29

2. Neil Kao, M.D.
Allergy and Clinical Immunology
Board certified for family care
Allergic Disease and Asthma Center
ADAC Research, PA

3. Disclosure Information
• I have no relevant financial relationships to disclose.
• I will not discuss off label use or investigational use in my presentation.
• I conduct clinical research with the following companies: ALK, AstraZeneca, GSK, Merck, Novartis,
Sanofi, Shionogi, Teva

5. hCOVID-19: major points of the lecture
1. SARS-CoV-2 spreads rapidly
2. Know the symptoms
3. COVID-19 is 10x more severe than influenza
4. Cf. flu: More contagious to others, higher rate of hospitalizations and death
5. Death rate much higher in elderly
6. Death rates seem to decline over time
7. Testing is essential to guide people and policies
8. Cancelling events and self-quarantining are important steps to take
9. Flatten the curve
10.Physical social distancing really helps
11.Asymptomatic people can spread the disease.

6. Epidemiology

7. More visualizations

8. COVID-19 effect on daily deaths

18. COVID-19: Diagnosis: Signs and symptoms
Fever, cough, severe illness 32% COVID
Fever + loss of smell ~100% COVID
ref.https://www.yahoo.com/lifestyle/im-doctor-sure-sign-covid-110159781.html
https://www.worldometers.info/coronavirus/coronavirus-symptoms/

19. COVID-19: anosmia
27x more likely to have, whereas 2.5x have fever, cough, respiratory difficulty
Temporary symptom for almost all
Olfactory epithelium does not have ACE2 receptors, hence are not affected
Cells that support epithelium have ACE2 receptors and are affected
Ref. https://hms.harvard.edu/news/how-covid-19-causes-loss-smell 7/24/20

22. Seasonal variations in the frequency of infections

23. COVID-19: disease severity
81% mild, 14% severe, 5% critical
The median time observed:
● from first symptom to → Dyspnea (Shortness of breath) = 5.0 days
● from first symptom to → Hospital admission = 7.0 days
● from first symptom to → ARDS (Acute Respiratory Distress Syndrome) = 8.0
days (when occurring)
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel
Coronavirus–Infected Pneumonia in Wuhan, China - JAMA, Wang et al., February
7, 2020

24. COVID-19: clinical facts
Duration of viral shed: up to 3 months
Duration of infectious: <10 days after symptoms begin. <20 days in people with
severe illness or severely immunocompromised
Amount of live virus from nose and throat drops significantly soon for COVID-19
symptoms start
REF. https://www.cdc.gov/media/releases/2020/s0814-updated-isolation-guidance.html

25. COVID-19: risk factors
I. Increased risk for severe illness:
II. Cancer, chronic kidney disease 4x, COPD, immunocompromised, obesity
(BMI>30) 3x [severe obesity (BMI>40) 4.5x], heart conditions, sickle cell, type
2 DM 3x
II. Might be at risk for severe illness:
Asthma 1.5x, cerebrovascular disease, cystic fibrosis, HTN 3x,
immunocompromised, neurologic, liver disease, pregnancy , pulmonary fibrosis,
smoking, thalassemia, type 1 DM 3x
III. 2 conditions 4.5x, =>3 conditions 5x

26. As of 2020May30, ref
https://www.cdc.gov/mmwr/volumes/69/wr/mm6924e2.htm

27. COVID-19: allergic rhinitis and asthma relationship
Korea, health insurance data, first study to look
Adult patients with allergic rhinitis, or asthma, even non-allergic asthma have
propensity for acquiring COVID-19, having a more severe clinical course, longer
hospital stays
Ref. accessed 2020Aug23
https://www.jacionline.org/article/S0091-6749(20)31136-2/pdf

31. COVID-19: males vs females

32. COVID-19: death rate
0.65% per 100 in the overall population for COVID
0.065% per 100 in the overall population for flu = 1/10th
https://www.bloomberg.com/opinion/articles/2020-08-06/revisiting-how-covid-19-ranks-with-seasonal-flu-and-1918-pandemic

33. COVID-19: pediatric death rates
Current total 121 deaths <21 y/o = 0.03% of total
Made of: 17 white (14%), 35 black (29%), 54 hispanic (45%)
General Population: white 50%, black 14%, hispanic 26%
>70% have 1 risk factor: asthma, obesity
Cause thought to reflect economic situation, not race

34. COVID-19: duration of symptoms
Study showed persisting lung and heart damage at 6 weeks, 12 weeks
Xray chest 88%, 56%
Breathlessness: 47%, 39%
:”long-haulers”: symptoms of fatigue and breathlessness persist for months after
infection
Ref. https://www.eurekalert.org/pub_releases/2020-09/elf-cps090320.php

35. COVID-19: thinning hair
27% of survivors report hair loss beginning 3-4 months afterwards, telogen
effluvum
Cause: stress
Treatments: none. This usually lasts for a few months
https://news.yahoo.com/freaking-covid-19-survivors-hair-153850699.html

37. Emergency Use Authorization definition & purpose
Created in 2004 as part of the Project Bioshield Act, amending the Food, Drug
and Cosmetic Act
EUA empowers the FDA Commissioner to grant permission to unapproved
products to be used in an emergency to diagnose, treat or prevent serious of life-
threatening conditions, when there are no adequate, approved and available
alternatives.
Rationale: randomized, controlled trials are the gold standard but sometimes you
have to act now with the best response you have currently
First used in 2005 to allow anthrax vaccine, due to attacks

38. COVID-19: overview tests available
1. Rapid antigen
2. Saliva antigen
3. Serum antibodies
4. PCR
5. Viral culture

39. COVID-19: SARS-CoV2 antigen tests have EUA
Only 4 to date (date granted EUA)
Quidel 5/8/20
BD 7/2/20
Lumiradx 8/18/20
Abbott 8/27/20
All screen for pieces of the virus
Ref. https://www.bioworld.com/articles/496872-lumiradx-scores-eua-for-point-of-care-covid-19-diagnostic-test

40. COVID-19: ID NOW Rapid Test
Example of one rapid test that will available during 9/20 at AFC Urgent Care
Results in <15 minutes
Can also test for influenza A & B, strep A, RSV
>7 million units shipped across all 50 states
There are others
Ref. https://www.abbott.com/IDNOW.html

41. COVID-19: BinaxNOW Ag card
EUA granted 8/26/20 to Abbott
Response in 15 min, cost “$5”, nasal swab, CLIA-waived, no machine
Specificity 97%, sensitivity 98% per data
Cons: “game changer”, only first 7 days of symptoms, not asymptomatic, any time
= screening any one. All have same (sensitivity, specificity), nasal swab, result
time
Confusion: earlier product ID Now was “less” accurate
Ref. https://www.fda.gov/media/141570/download

44. COVID-19: saliva tests
Detect pieces of virus in saliva, like rapid antigen tests, in sterile
container
Fifth saliva test to receive EUA given special mention, because no kit
is needed to get nucleic acid extraction
This eliminates 1 step, which requires reagents, that have had
shortages
Name: SalivaDirect, inventor Yale School of Public Health
Ref. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-
emergency-use-authorization-yale-school-public-health

45. COVID-19: antibody tests
<175 test developers sell tests and can legally market their antibody tests without
having their validation data evaluated by the FDA, since 3/20.
Many have high false positive results up to 15-20%.
Ideally false positive rates should be <5%, ideally <2%
Few assays have requested EUA from the FDA, which verify test results
independently
Ref. https://www.cnn.com/2020/04/28/health/coronavirus-antibody-tests-terrible/index.html
https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html

46. COVID-19: antibody tests 2
No advantage whether assays test for IgG, IgM and IgG
No evidence serological tests can show whether a person has immunity or is no
longer at risk of becoming reinfected.
Some patients have no detectable antibody response
In certain populations, tests may be wrong up to half the time, per CDC
Idea of “Antibody passport” rejected by all experts
Ref. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html
https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19

47. COVID-19: Diagnosis: where to get tests
Each hospital system has designated testing centers and hospitals where COVID
patients are treated
Independent physicians offices may be
SC DHEC has mobile clinics at rotating sites across the state.
https://www.scdhec.gov/infectious-diseases/viruses/coronavirus-disease-2019-covid-19/covid-19-screening-testing-sites
Be wary of where rapid tests are done, because they are not equally reliable
GOLD standards are PCR and culture, which are now done less and less,
basically for hospitalized patients, persistent disease, surveillance

50. COVID-19: CDC statement of who should get tested
8/24/20 Any one symptomatic should get tested, self-quarantine at home until
getting test results, speak with health care provider. Today’s update, seemed to
lessen the importance of testing when exposed and asymptomatic. There is
considerable pushback from non-government experts = controversy
Prior statement: If exposed, and even asymptomatic, should get tested. Reason:
asymptomatic spread is possible, and if not tested, could then go on to spread to
others. Vicious cycle. Experts support this still.
Ref. https://www.vox.com/2020/8/26/21403000/trump-covid-coronavirus-testing-cdc-hhs

51. COVID-19: when are patients most contagious?
CDC says when symptoms first begin and for the next 3 days then the amount of
virus falls off
Other sources and sites estimate virus shedding begins on average 2 days prior to
onset of symptoms and lasts up to 10 days total, unless the patient has a severe
case or is immunocompromised. No cases exceed 14 days
Note CDC estimates that one infected person may spread COVID to up to 4 more
people
CDC estimates that 40-45% of people with COVID-19 are asymptomatic, which
makes tracing and prevention difficult.

52. COVID-19: ICD10 and CPT codes to know
I. ICD10: U07.1 acute respiratory disease COVID-19
There are other codes for other diagnoses or symptoms
II. CPT: 87635 infectious agent detection by nucleic acid; severe acute
respiratory syndrome coronavirus 2, amplified probe technique
There are other codes for other tests
Ref. https://www.ama-assn.org/system/files/2020-08/cpt-assistant-guide-coronavirus-august-
2020.pdf?utm_source=College+Insider&utm_campaign=758491da45-
EMAIL_CAMPAIGN_2020_02_11_04_00_COPY_01&utm_medium=email&utm_term=0_824f79a3c1-758491da45-142521350,
https://www.aapc.com/covid-19/

53. COVID-19: coding and reporting guidelines
Do not use U07.1 unless diagnosis is confirmed by test, even if asymptomatic
Z20.828 actual exposure to confirmed or suspected COVID-19
Z03.818 possible exposure to COVID-19, ruled out, observation
Z11.59 no exposure, screening, tests can be unknown or negative
Ref: https://www.cdc.gov/nchs/data/icd/COVID-19-guidelines-final.pdf

54. COVID-19: Pop Quiz 1: Names
What is the origin of the name COVID-19?
Corona virus disease was discovered in 2019
What was the interim name for this virus? 2019-nCoV (n = novel strain)
What is the cause of this disease?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Ref. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-
guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it

55. Dum spiro spero (latin)
While I breathe, I hope

56. COVID-19: CDC How to Protect Yourself & Others
1. Wash your hands often
2. Avoid close contact (>6 feet rule)
3. Cover you mouth and nose with a mask when around others
4. Cover coughs and sneezes
5. Clean and disinfect
6. Monitor your health daily
Ref. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html

57. COVID-19: CDC Quarantine guidelines
Who? Close contact with any one who has COVID-19
How long? 14 days after last contact with person diagnosed with COVID-19
and until 24 hours after their fever subsides with meds
Other steps? Monitor daily for signs and symptoms of COVID-19.
Minimize close contact with others.
Seek medical care if signs and symptoms worsen
Begin sterilization and tracing measures
Ref. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html (2020 Aug 16)

58. COVID-19: What is N95 filtration efficiency?
Coronavirus size 0.125 microns, but N95 masks filter 95% of particles 0.30
microns, so N95 masks do not filter out coronavirus-sized particles
False, because 1) particles move in erratic Brownian motion and 2) mask material
also uses electrostatic attraction. Result: filtration is very effective
So what’s the problem(s)? Short supply (replace, priority), tight fit necessary
Ref. https://www.usatoday.com/story/news/factcheck/2020/06/11/fact-check-n-95-filters-not-too-large-stop-covid-19-
particles/5343537002/

59. COVID-19: face masks
Face mask brackets: warned against using, must had a tight fit for mask to be
effective. No sign they improve efficacy
Face shields and masks with valves do not protect people around you well.
N95 mask filters 95% of small particles. Loses ~⅓ filtering potential if fit is improper
Even prolonged wearing of face masks do not cause hypoxia or CO2 retention
(hoax), just fatigue and sweating from the increased work of breathing
Ref. https://www.medscape.com/viewarticle/935521, https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-
cover-guidance.html#masks-with-vents https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-
coverings.html?utm_source=College+Insider&utm_campaign=a788c4b95b-
EMAIL_CAMPAIGN_2020_02_11_04_00_COPY_01&utm_medium=email&utm_term=0_824f79a3c1-a788c4b95b-142521350
https://www.cdc.gov/niosh/topics/hcwcontrols/recommendedguidanceextuse.html

61. COVID-19: nasal rinses
No studies
Analogy wash dirt off hands, so wash face
and nasal mucosa, especially posterior, of
any accumulated viruses and bacteria
May safely use water, saline, or very dilute
essential oils
Nose > lung infectivity
Ref. https://www.cell.com/cell/fulltext/S0092-8674(20)30675-9

62. COVID-19: Mouthwashes
Goals: to prevent infections and to reduce viral load in throat
Problem: temporary effect and more virus are produced
After 30 seconds in vitro, completely eliminated active virus, by Dequonal, Iso-
Betadine mouthwash, Listerine Cool Mint. Five other brands has lesser effects
Clinical correlation being investigated
No comment by CDC
Bottom line: won’t hurt, can help, inexpensive, easy, should do it, like hand
washing
Ref. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa471/5878067

63. COVID-19: importance of concept: viral load

64. COVID: EPA approved disinfectants
Initially confusion, because no products had been tested formally for COVD-19
testing. The EPA released a list of products that were expected to be effective,
because they were effective against similar viruses.
“All products on this list meet EPA’s criteria for use against SARS-CoV-2, the virus
that causes COVID-19”
Be aware of fraudulent products and scams, e.g. hand sanitizers using methanol
instead of ethanol
Ref. https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2-covid-19

65. COVID-19: FDA warnings
1. Hand sanitizer sold in containers mimicking commercially available food and
drink, with cases of accidental ingestion
2. https://www.aol.com/article/lifestyle/2020/08/28/fda-warning-about-hand-sanitizers-packaged-like-food-and-drinks-has-experts-
alarmed-this-is-super-scary/24603117/

66. COVID-19: SC DHEC guidelines for schools
Worldwide, societal problem
Every institution, student, and family has their own unique set of variables to
consider, when deciding if and how much in person attendance
General agreement:
1. do physical distancing, minimize contact time, individualize
2. Be flexible, because unexpected change is part of the life equation
Ref. https://www.dhec.sc.gov/infectious-diseases/viruses/coronavirus-disease-2019-covid-19/schools-childcare-centers-covid-19

67. COVID-19: Dental practice guidelines
Patient screening
Guidelines for PPE
General guidelines, individualized for dental practices
Cleansing of tools
No data on transmission at practices
Ref.: https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.html 2020 Aug 04

70. Those who can not remember the past
are condemned to repeat it
George Santayana

72. COVID-19: laughter therapy
Stress levels are high and this adversely affects the immune system when we
need it at its strongest
Benefits: less muscle tension, lower P and BP, better mood with less depression
and anxiety
What else have we got if not infected, or asymptomatic, or mildly symptomatic?

74. COVID-19: secondary treatments
Convalescent plasma
Remdesivir
dexamethasone
Ref. https://emedicine.medscape.com/article/2500116-overview as of 9/2/20

76. COVID-19: Withdrawn EUA
Hydroxychloroquine: granted EUA 3/28/20 and withdrawn 6/15/20 due to serious
side effects
Hydroxychloroquine with azithromycin: no evidence.
7/4/20 WHO discontinued 2 treatment arms of 1) hydroxychloroquine and 2)
lopinavir/ritonavir in its worldwide SOLIDARITY trial, citing no benefit
Selected diagnostic tests (antigen swab, antibody blood)
Select KN-95 masks from China

77. COVID-19 Redesivir trial
Open-label, severe, pneumonia + hypoxia, given IV remdesivir 5 or 10 days
Median time to recovery was significantly different:
Remdesivir 11 days vs. placebo 15 days for recovery
Rate ratio for recovery 1.32 (P<0.001)
DSMB reviewed interim data and recommend early stoppage, inform NIAID
4/27/20, results made public 4/29/20
Ref. https://covid-slides.idea.medicine.uw.edu/uploads/2/remdesivir__master.pdf

78. Remdesivir for the Treatment of Covid-19 (ACTT-1):
Results, Days to Recovery
Source: Beigel JH, et al. N Engl J Med. May 22, 2020. [Epub ahead of print]

79. COVD-19: Remdesivir
RNA polymerase inhibitor with demonstrated efficacy in vitro and in animals models
5/1/20 granted EUA only for patients with severe COVID-19, specifically, COVID-19
patients with low blood oxygen levels or who need oxygen therapy or mechanical
ventilation [prelim]
5/27/20 https://www.nejm.org/doi/full/10.1056/NEJMoa2015301?query=featured_home
CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation,
our trial did not show a significant difference between a 5-day course and a 10-day
course of remdesivir. With no placebo control, however, the magnitude of benefit
cannot be determined.
8/28/20 granted EUA for all hospitalized COVID-19 patients

80. COVID-19: Convalescent plasma
Conclusion: This “may be effective in lessening the severity or shortening the
length of COVID-19 illness in some hospitalized patients.”
Indication: “Suspected or lab-confirmed COVID-19 in hospitalized patients with
COVDI-19”
Place in treatment: no comment as to whether this can be given before,
concurrently, or after remdesivir
Emergency Use Authorization granted 23 Aug 2020
Ref. https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-convalescent-plasma-
potential-promising-covid-19-treatment

81. COVID-19: Convalescent plasma clarifications
Not randomized, multivariate analysis not done, relative risk not absolute risk, no
other confirmatory studies, Data from prelim study, Mayo Clinic, small subset, no
difference in death rates
Stats: RRR 35% not ARR, misleading
Authors Dr. request clarifications
"The results are not conclusive," WHO’s chief scientist Dr. Soumya Swaminathan
said during a press briefing. "At the moment, it’s still very low-quality evidence.”
Other experts suspect “benefit will be modest at best”: 5 per 100 doses

83. COVID-19: convalescent plasma pros and cons
Con: people get plasma, won’t participate in other trials
Get vaccine, same
Focus on 1 vaccine, can’t do other trials, when no clear answer yet only EUA,
surely other improvements will come,exclusion criteria

84. COVID-19: Convalescent plasma NIH report
“”There are currently no data from well-controlled, adequately powered
randomized clinical trials that demonstrate the efficacy and safety of convalescent
plasma for the treatment of COVID-19.
9/1/20
Ref. https://www.covid19treatmentguidelines.nih.gov/statement-on-convalescent-
plasma-eua/

85. COVID-19: dexamethasone in ARDS
Patients: hospitalized patients in UK
Intervention: Dexamethasone 6 mg once day for <10 days
Primary outcome: all-cause 28-day mortality
Result: significantly lower in treatment group (on vent, oxygen),
no difference if not receiving any respiratory support
Comment: only therapy to date demonstrating low mortality.
7/17/20
Ref. https://www.nejm.org/doi/full/10.1056/NEJMoa2021436

86. COVID-19: dexamethasone on mortality
Meta-analysis of 7 studies of severely ill patients with COVID-19
1,703 patients, 28-day all-cause mortality
Odds ratio with corticosteroids 0.66 (P<0.001)
Treated patients had fewer serious adverse effects
Interpretation: treated patients had 20% lower risk of death. = 87 fewer deaths per
1,000. = 68% of severely ill patients survive versus 60%
WHO updated its treatment advice the same day results were announced
9/2/20 Ref. https://jamanetwork.com/journals/jama/fullarticle/2770279 https://www.reuters.com/article/us-health-coronavirus-
steroids/steroids-cut-death-rates-among-critically-ill-covid-19-patients-major-study-finds-idUSKBN25T20D

87. COVID-19: adjunct treatments
No evidence to support use:
Vitamin C, D, zinc, ivermectin, antiviral HIV antiprotease inhibitors,
Ongoing trials: tocilizumab/IL-6, janus-kinase (JAK) inhibitors, monoclonal
antibodies against COVID-19
May take acetaminophen, ibuprofen
Ref. https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ https://covid-19tracker.milkeninstitute.org/

89. COVID-19: reinfection
8/19/20: Do not know. Complicated situation.
Some can test positive for up to 3 months after diagnosis and not be infectious.
No proof they are immune to reinfection
No one has ever had a documented case of reinfection
Evidence: Two cultures, preferably with RNA analysis demonstrating different
strains
If after 3 months, suspect COVID-19 with no other explanation, then re-test
Ref: https://www.cdc.gov/media/releases/2020/s0814-updated-isolation-guidance.html

90. COVID-19: Reinfection cases
8/2/20 First case in world, Hong Kong 41 y/o man, 140 days,
had milder course
8/24/20 First case in Netherlands, announced, patient,
2nd + 6/6/20, 48 days, hospitalized for oxygen [pre-print Lancet]https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3681489
8/25/20 First case in US in 25 y/o male Nevada, 48 days,
hospitalized for oxygen
8/26/20 Four cases in Netherlands, elderly

91. COVID-19: Reinfection conclusions
1. Can happen
2. Severity of second course varies
3. Experts still think normal immune systems mount an adequate response
4. Too few have occurred to detect a pattern as of yet
5. Emphasis on same primary prevention, early detection by testing, supportive
care, monitor and seek care when vitals and/or sign deteriorating

93. COVID-19: how to get herd immunity
Definition: the point at which enough people in a population are immune to a
disease, which by infection or vaccination, that the pathogen cannot easily spread
through the community and cause new outbreaks.
Infection would involve staggering numbers of people of all age groups risking
serious illness and death. Not the way to go, e.g. Sweden
Experts estimate we need about 70% immune for herd immunity, current 9.3%
US population 330 million. >6 million confirmed cases = 2%. Even if 10x are
actually ill and recovered = 20%.
Conclusion: Vaccination of about 50% necessary to stop successive waves

95. COVID-19: Operation Warp Speed Overview
3/27/20 Congress allocates $9.5 billion, partners HHS, FDA, other agencies
GOAL: 300 million doses of safe & effective vaccine by January 2021
5/15/20 President Trump announces public-private partnership. Pick 5+
6/30/20 FDA efficacy bar: demonstrate >50% effective to gain approval, in at
least diminishing the severity of COVID-19 symptoms
Key areas: development, manufacturing, and distribution, getting advice from
scientists, physicians, and military officers
Will not partner with Chinese vaccine programs, European Commission, or WHO
Ref. https://www.hhs.gov/about/news/2020/06/16/fact-sheet-explaining-operation-warp-speed.html

98. COVID-19 Warpspeed: 9 Companies selected
Moderna/NIAID
Pfizer-BioN Tech
AstraZeneca-University of Oxford
Johnson & Johnson/Janssen
Merck and IAVI
Sanofi and GSK
Novavax
Vaxart
Inovio
8/30/20
Note: vaccines from other countries are not listed
Ref, https://en.wikipedia.org/wiki/Operation_Warp_Speed#Funded_companies

99. Vaccines: types available currently
type example con
Live, attenuated MMR, varicella immunocompromised
inactivated polio
Toxoid (weakened toxin) DTaP
subunit Pertussis subunit in DTaP
conjugate HiB

101. COVID-19: vaccines
1. Development typically takes >10 years and costs >$500 million
2. Myriad other logistical, ethical, financial issues:
Who gets first, production problems, pay for, will people even get, what about
other countries, China, Russia have their own vaccines. Complacency,
inconvenience, lack of confidence (10-20%) in western countries
1. https://www.weforum.org/agenda/2020/06/vaccine-development-barriers-coronavirus/
Dangerous rush 8/21/20 https://science.sciencemag.org/content/369/6506/885.full
Different technologies used to measure neutralizing antibodies, so this can’t
be used to compare vaccines. Only actual infection rates

102. COVID-19: vaccine Pfizer/BioNTech
Mechanism of 4 vaccines, each uses mRNA in different combinations to targeted
antigens, which are produced, immune system responds
US Phase 2-3 trials started 7/27/20
Con: never been tried before; long-term shortage + shipping requires -94 degrees
+ used within 24 hours of thawing, special equipment needed to maintain the “cold
chain”

103. COVID-19: vaccine Moderna/NIAID
Mechanism: contains mRNA for spike protein, copies of spike made
US Phase 2-3 trials started 7/27/20
Con: never been tried before; shipping -4 degrees F, then refrigerator temps for 7
days possible
Ref. https://www.bloomberg.com/features/2020-covid-vaccine-manufacturing-essentials/

104. COVID-19: Vaccine AstraZeneca & U. of Oxford
8/24/20 to date about 10,000 subjects enrolled, whereas normally 30,000 subjects
should be enrolled for standard approval
Don’t approve vaccine until have adequate signals of safety and efficacy
Approval will shut off research by other makers
Mechanism: weakend adenovirus, from chimpanzees, which can’t replicate,
combined with genes of spike protein
Start US phase III trials 9/1/20

105. COVID-19: AstraZeneca/U. Of Oxford vaccine (2)
Trials halted 9/8/20 due a reported serious adverse event.
9/5/20 37 WF hospitalized with transverse myelitis, investigators notified 9/11/20
Trials reactivated 9/13/20 in UK, not US as of yet
Fauci opinion “one-off”
Turns out a second woman also had transverse myelitis, but no details released
Ramifications: companies under pressure to be more transparent with blueprints
AZ:https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-
cece903592b9/D8110C00001_CSP-v2.pdf

106. COVID-19: Johnson and Johnson/Janssen vaccine
4th vaccine to enter phase 3 trials, started 9/23/20
Mechanism: recombinant vector vaccine. uses a human adenovirus to express the
SARS-CoV-2 spike protein in cells. Adenoviruses are a group of viruses that
cause the common cold. However, the adenovirus vector used in the vaccine
candidate has been modified so that it can no longer replicate in humans and
cause disease
Advantage: Single dose, refrigerate only
Ref. https://www.nih.gov/news-events/news-releases/fourth-large-scale-covid-19-vaccine-trial-begins-united-
states

107. COVID-19: vaccine controversies
1. Time: Normal vaccine development takes 10-17 years. Coronavirus vaccine
development is being compressed into <1 year.
2. Safety: not much time or number of patients to monitor for adverse effects
3. Efficacy: FDA bar set low, hopefully beneficial effect is greater than this,
especially in elderly, and longer lasting
4. Politics: qualifications of leaders and insider trading
5. This is not the end. Competition necessary to develop better products in
future
6. Antivaccine movement current + future hesitancy (no confidence, denial).
Poll: only ½ of people would get vaccinated

108. COVID-19: vaccines
8/30/20 head of US FDA said that coronavirus vaccines may be given EUA before
phase 3 trials are complete.
Trials could be ended early the independent Data and Safety Monitoring Board if
the data show the vaccine is ovewhelmingly safe and effective per Fauci 9/1/20
Examples: Cutter incident 1955 40,000 children got polio
swine flu pandemic 1976 did not occur, 1:100,000 got Guillian-Barre
Who gets first? priority?
Ref. https://www.cnn.com/2020/09/01/health/eua-coronavirus-vaccine-history/index.html

109. COVID-19: vaccines other mechanisms of action
Inovio: DNA given, replicated, body recognizes as forgein, stimulates natural immune
response (SNIR)
Merck/IAVI: modified measles virus is used to deliver pieces of coronavirus, then SNIR
Novavax: give pieces of spike protein to SNIR
Sanofi/GSK: weakened adenovirus + adjuvant, that SNIR
Vaxart: oral tablet, has been proposed for influenza, may offer logistic advantages

110. COVID-19: Vaccine logistics
Production and distribution chain are mind-bogglingly complex with time frame
Opinion: who gets it first: front-line health care workers, first-responders, high risk
patients.
Large scale availability in 2021
Political noise: announcement end of 10/22/20 by EUA per FDA advisory committee
Trying to build public trust in the process and vaccines
Ref. https://www.msn.com/en-us/health/health-news/mind-bogglingly-complex-here-s-what-we-know-about-how-covid-vaccine-will-be-
distributed-when-it-s-approved/ar-BB18L0hZ?ocid=msedgntp

113. Epidemiological curve

116. COVID-19: what is the value of a single life lost?
The calculus of death
varies, because of
assumptions made.
Estimates vary from <$1
to $10 million, with an
average of $4 million per
a 60 y/o

117. COVID-19: calculate: is lockdown worth it?

118. Printed Statements by White House and
CDC, somes states, not SC
Ref. https://www.whitehouse.gov/openingamerica/
4/16/20,
https://www.cdc.gov/coronavirus/2019-
ncov/downloads/php/CDC-Activities-
Initiatives-for-COVID-19-Response.pdf
see table 1, 5/2

120. COVID-19: what could happen this fall and winter?
Potential for simultaneous COVID-19 surge (2nd wave) + traditional rhinovirus,
RSV + influenza seasons “ https://www.webmd.com/lung/news/20200812/redfield-this-fall-could-be-the-worse-weve-
seen
Epidemiologists are worried. Historically, flu 2nd wave was worse and had a
higher mortality in younger adults cf. 1st wave
Look to Southern hemisphere (Australia, Chile, South Africa)
So far minimal flu activity seen <1% of normal, for unknown reasons
Why? Partly reduced from physical distancing due to COVID-19

121. COVID-19: with influenza “twindemic”
Spector of another wave of COVID overlapping with annual flu season: morbidity
and deaths from single infections and co-infection.
Flu vaccinations are an important way to reduce this event
Vaccine effects usually last 6 months, in younger adults, shorter if elderly
Peak months are Jan - March historically
CDC says get during September to October
PLAN: watch news and adjust, get flu vaccine late October to early November,
elderly get Fluzone High-Dose
Can’t protect you directly from COVID-19, but can reduce chance of a weakened
immune system, which if gets COVID-19, now higher chance of death

123. COVID-19: caregiver burnout
Real phenomena: counselors say the largest group of new patients are health
care professionals, not the general public
Areas affected: mental, emotional, physical health, and relationships
Take proactive steps for yourself and to support your network
Have everyone be aware and pitch in

124. COVID-19: information sources
1. Health care-based individuals and societies (prevent & care for sick)
2. Economics and companies (business $)
3. Politicians (most countries and cultures prioritize business over health,
concern: getting re-elected depends on the state of the economy)
4. Pop culture (celebrities, hoaxes, rumors, social media, commercial
journalism)
Be very careful with your information sources. Try to select group 1) as your
source of information & their analysis and opinions.

125. COVID-19: Websites for information
1. WHO https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2. CDC https://www.cdc.gov/coronavirus/2019-ncov/
3. NIH https://www.covid19treatmentguidelines.nih.gov/
4. SC DHEC https://www.scdhec.gov/infectious-diseases/viruses/coronavirus-disease-2019-covid-19
5. Accelerate SC https://accelerate.sc.gov/ https://acceleratesc.org/
6. Johns Hopkins University stats
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
7. Non-governmental (non-political) scientific and medical websites: Infectious
Disease Society of America https://www.idsociety.org/covid-19-real-time-learning-network/

126. hCOVID-19: major points of the lecture
1. SARS-CoV-2 spreads rapidly
2. Know the symptoms
3. COVID-19 is 10x more severe than influenza
4. Cf. flu: More contagious to others, higher rate of hospitalizations and death
5. Death rate much higher in elderly
6. Death rates seem to decline over time
7. Testing is essential to guide people and policies
8. Cancelling events and self-quarantining are important steps to take
9. Flatten the curve
10.Physical social distancing really helps
11.Asymptomatic people can spread the disease.

127. Let us be up and doing
With a heart for any fate,
Still achieving, still pursuing,
Learn to labor and to wait.
Henry Wordsworth Longfellow
A Psalm of Life