COVID-19

COVID 19 Briefing

By Erik McLaughlin MD, MPH

Saturday, March 7, 2020

Table of Contents

Clinical Aspect 4

Summary. 4

Virus Family and Genealogy. 4

Signs and Symptoms. 5

Testing Guidelines. 5

Treatment Guidelines. 6

Special Populations. 7

Infection Control and Prevention. 8

Emerging Treatments. 10

Vaccines Potential 10

Public Health Aspect 10

Summary. 10

Cases and Epidemiology by Geography. 11

Communicability and Quarantine. 11

Case Fatality Rates. 12

Comparison to Other Major Viruses. 12

Social Impact 13

Summary. 13

Politeness vs. Protection. 14

Mass Gatherings. 14

Special Events. 14

Personal Space and Distance. 14

Workplace Interactions. 14

Social Interactions. 14

School Closures. 14

Business Impact 15

Summary. 15

Supply Chain Disruption. 15

Workforce Disruption. 16

Tele-Commuting. 17

Food Security. 17

Loss of Maintenance Services. 18

Emerging Markets. 18

Declining Markets. 18

Resource Poor Countries. 18

Environmental Impact 18

Summary. 18

Animal Infections. 19

Waste Management and Processing. 19

Seasonality of Viral Infections. 19

APPENDIX A. 20

Initial Planning Stages. 20

Initial Targets. 20

Cohorting Patients in Hospital Plan. 20

Preparing Staff and Volumes of Patients. 21

Prepare for Allocation of Resources. 21

Sample Ed Triage Concepts. 21

Patient Flow in Triage Centers. 22

Response interventions. 22

Anticipation. 22

Early Detection. 22

Containment 23

Control and Mitigation. 23

Elimination or Eradication. 23

Four Main Response Teams and Goals. 24

Coordinating Responders. 24

Health Information. 24

Communicating Risk and Controlling “Infodemics”. 25

Health Interventions. 25

Basic Concepts. 25

Grading the Severity of Impact 25

Epidemic Phases. 26

Field Epidemiology. 26

Additional Resources. 27

Protocol for Treatment of Confirmed COVID-19 Infection. 34

 

Clinical Aspect

 

Summary

  • The name of the virus is “SARS-CoV-2 and the disease caused by it is COVID-19
  • From the Coronavirus family and related to MERS-CoV and SARS CoV
  • Frequently reported signs and symptoms include fever (83–98%), cough (46%–82%), myalgia or fatigue (11–44%), and shortness of breath (31%) at illness onset[i]
  • Spread via respiratory droplets in the air and from touching contaminated surfaces
  • Incubation period of 2-14 days is current most accurate data
  • Developing and distributing a reliable test has been a struggle
  • At present, treatment is largely supportive care (fever control, hydration and rest)
  • Patients with a mild clinical presentation may not initially require hospitalization. Clinical signs and symptoms may worsen with progression to lower respiratory tract disease in the second week of illness1
  • Deaths associated with COVID-19 are most commonly from Adult Respiratory Distress Syndrome (ARDS) and sepsis
  • Data from Italy looks at 10% of all positive patients requiring Intensive Care (ICU) Support[ii]
  • Elderly patients and medically fragile people appear to have the greatest risk of complications and mortality
  • The current best protection is to avoid sick people, wash your hands, avoid touching your face, eyes, nose and mouth and to cover your cough and sneeze
  • Clean frequently touched surfaces with commercial household cleaning solutions
  • Surgical masks are for those already with symptoms and not required for uninfected people in the general population.
  • Healthcare workers should adhere to strict contact, airborne and eye protection precautions
  • Vaccine development is currently underway
  • Treatment medications, antivirals and patient care protocols are being developed and studied

 

Virus Family and Genealogy

  • Newly recognized nomenclature is the name of the virus is “SARS-CoV-2 and the disease caused by it is COVID-19”.[iii]
  • Non-segmented RNA virus
  • Binds via ACE-2 (angiotensin converting enzyme 2) found on Type II alveolar cells and intestinal tissue[iv]
    • Same receptor used by SARS
  • Viral respiratory illness from the Coronavirus family
    • COV19 is previously unrecognized in humans[v]
  • Spread from human to human via respiratory droplets
  • Symptoms can appear 2-14 days after exposure[vi]
    • Limited reports show an incubation period of up to 27 days[vii]
  • Reports are emerging of two related but separate strains of SARS-CoV-2[viii]
    • “L-type”
      • Dominant strain in early days of the Wuhan outbreak
        • Now not as common, globally
        • Believed to have evolved from S-type
      • “S-type”
        • More commonly seen globally as pandemic spreads
        • More closely resembles coronavirus from bats and pangolins
        • May have been circulating for a longer period than known
          • Clinically undetected in human population
        • Researchers are in disagreement on accuracy of this report[ix]
      • SARS-CoV-2 is related to Middle East Respiratory Syndrome (MERS-CoV)[x]
        • Emerged in 2012 in Saudi Arabia
        • Regional cases include Bahrain, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, United Arab Emirates (UAE), and Yemen[xi]
        • 2494 confirmed cases
        • 858 attributable deaths and case fatality rate of 34.4%
      • SARS-CoV-2 is related to Severe Acute Respiratory Syndrome (SARS CoV)
        • Emerged in 2003 in Guangdong province, southern China[xii]
        • Thought to be an animal virus that spread to humans
        • Spread to more than 24 countries (Asia, Europe, North America, South America)
        • Mean incubation period of 5.7 days[xiii]
        • 8094 confirmed cases
        • 774 attributable deaths and case fatality rate of 9.6%
        • No cases reported since 2004

 

Signs and Symptoms

  • Common symptoms include fever, cough and shortness of breath[xiv]
    • Fevers are considered a temperature greater than 38 C or 100.4 F
  • Frequently reported signs and symptoms include fever (83–98%), cough (46%–82%), myalgia or fatigue (11–44%), and shortness of breath (31%) at illness onset[xv]
  • Radiology exam with Chest CT scans shows 78% of known cases with either ground-glass appearance and/or consolidation on imaging [xvi]
  • Cause of death due to CoVID-19 is typically from Acute respiratory Distress Syndrome (ARDS) and sepsis11
  • In one report, among patients with confirmed COVID-19 and pneumonia, just over half of patients developed dyspnea a median of 8 days after illness onset11
  • Clinical signs and symptoms may worsen with progression to lower respiratory tract disease in the second week of illness11
  • Data from Italy indicates 10% of all positive patients require intensive care unit (ICU) support [xvii]

Stages of Illness

  • Replicative stage[xviii]
    • Viral replication occurs over several days. Host immune response fails to contain the virus and relatively mild symptoms may occur
  • Adaptive immunity stage
    • As a stronger immune response begins to work, titers of the virus begin to fall. However, this also may lead to increased levels of inflammatory cytokines and subsequent tissue damage.
    • This is the proposed explanation for patients are relatively stable for several days only to suddenly deteriorate when they enter this stage. [xix]
  • Understand these stages are important for the following reasons[xx]
    • Initial symptoms do not predict possibility for future deterioration
    • Risk stratification will become increasingly important
    • Early antiviral therapy will likely play a more important role during the early replicative stage
    • Low dose steroids (immunosuppressive therapy) could be initiated during the adaptive immune stage to try and blunt the overwhelming immune response. (speculative)

 

Testing and Guidelines

  • Centers for Disease Control (CDC) currently has a packaged kit for testing of patients who meet current criteria
  • Current criteria for testing is evolving and at time of writing is based on February 27, 2020 guidelines.[xxi]
    • Presence of clinical lower respiratory symptoms (cough, shortness of breath or fever) and known contact with confirmed case
    • Fever and lower respiratory symptoms requiring hospitalization and travel from affected areas (China, Iran, Italy, Japan, South Korea)
    • Fever with sever, acute lower respiratory illness requiring hospitalization and without alternative explanatory diagnosis and no source of exposure identified
    • These testing guidelines are already out of date as of March 7th 2020
  • “Centers for Disease Control and Prevention (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel.” It is intended for use with the Applied Biosystems 7500 Fast DX Real-Time PCR Instrument with SDS 1.4 software. This test is intended for use with upper and lower respiratory specimens collected from persons who meet CDC criteria for COVID-19 testing. [xxii]
  • As of February 3rd 2020 an emergency use authorization (EUA) was granted for the use of unapproved, but potentially life-saving medical or diagnostic products during a public health emergency14
  • 40 state public health labs can begin testing for COVID-19 using parts of the original CDC test[xxiii]
  • There has been difficulty in developing an accurate test as this is a new pathogen
  • A goal of being able to perform 10,000 tests per day is considered a minimum
  • Snapshot of current testing activity by country as of March 2, 2020[xxiv]
    • South Korea
      • 109,591 tests performed
      • 2,138 tests per million people
    • Italy
      • 23,345 tests performed
      • 386 tests per million people
    • Austria
      • 2,120 tests performed
      • 235 tests per million people
    • Switzerland
      • 1,850 tests performed
      • 214 tests per million people
    • UK
      • 13,525 tests performed
      • 199 tests per million people
    • Finland
      • 130 tests performed
      • 23 tests per million people
    • Vietnam
      • 1,737 tests performed
      • 18 tests per million people
    • Turkey
      • 940 tests performed
      • 11 tests per million people
    • United States
      • 472 tests performed
      • 1 test per million people
    • Number of tests and positivity rate for COVID-19 as of February 26th[xxv]
      • UK
        • 7,132 tests
        • 470 positives
        • 2% positivity rate
      • Italy
        • 9,462 tests
        • 470 positives
        • 5% positivity rate
      • France
        • 762 tests
        • 17 positives
        • 2% positivity rate
      • Austria
        • 321 tests
        • 2 positives
        • 6% positivity rate
      • South Korea
        • 66,562 tests
        • 1766 positives
        • 25,568 awaiting results
        • 3% positivity rate
        • Currently testing approximately 10,000 per day
        • Goal of increasing testing to 15-20,000 per day as of Feb 27th, 2020
      • United States
        • 445 concluded tests
        • 14 positives
        • 1% positivity
        • March 2nd FDA commissioner announced US will have ability to perform 1 million tests within the week
        • 12 of more than 100 public health labs in USA are able to currently test
        • The CDC can only screen 350-500 samples per day

 

Treatment Guidelines

  • Current guidelines are based off February 11, 2020 CDC guidelines[xxvi]
    • Hospitalized patients should be treated in an Airborne Infection Isolation Room (AIIR) with standard contact, airborne and eye protection precautions
  • At present, treatment is largely supportive care for non-ICU level cases
    • Fever control with antipyretics such as acetaminophen and ibuprofen
    • Hydration either oral or Intravenous (IV) routes
    • Respiratory support up to intubation and mechanical ventilation
    • There are current studies underway for antiviral medications (see below)
  • Patients with a mild clinical presentation may not initially require hospitalization. Clinical signs and symptoms may worsen with progression to lower respiratory tract disease in the second week of illness[xxvii]
  • Possible risk factors for progressing to severe illness may include, but are not limited to, older age, and underlying chronic medical conditions such as lung disease, cancer, heart failure, cerebrovascular disease, renal disease, liver disease, diabetes, immunocompromising conditions, and pregnancy17
  • In another report, the mean time from illness onset to hospital admission with pneumonia was 9 days17
  • 20% of infected patients require hospitalization17
    • 20-32% of hospitalized patients require ICU level support for respiratory problems 17
  • Acute respiratory distress syndrome (ARDS) developed in 17–29% of hospitalized patients, and secondary infection developed in 10%.17
  • Cytokine Storm concept
    • Similar to features of bacterial sepsis or hemophagocytic lymphohistocytosis (HLH)[xxviii]
    • Clinical features can be tracked with C-reactive protein (CRP) and ferretin
      • Correlate with disease severity and mortality
    • In one study, among critically ill patients admitted to an intensive care unit, 11% received high-flow oxygen therapy, 42% received noninvasive ventilation, and 47% received mechanical ventilation.17
    • Some hospitalized patients have required advanced organ support with endotracheal intubation and mechanical ventilation (4–10%), and a small proportion have also been supported with extracorporeal membrane oxygenation (ECMO, 3–5%).17
    • Other reported complications include acute cardiac injury, arrhythmia, shock, and acute kidney injury.17
    • Prone ventilation for ICU/ventilated patients has been show as a promising adjunct[xxix]
    • Lower tidal volumes of 4-8mL/kg are advised[xxx]
    • Lower inspiratory pressures (<30 cmH20) are also advised[xxxi]
    • Patients with moderate to severe ARDS are advised to be treated with higher PEEP (positive expiratory end pressure)
    • Avoid routine use of continual infusion of neuromuscular blockade agents

 

Special Populations

  • Children
    • A recent study from China showed only 1% of infections were in children <9 years old[xxxii]
    • The same study showed only 1% of infections were in children 10-19 years old
    • Mortality increases with age
    • There have been no reported deaths in children less than 9 y/o
    • Children 10-19 years old have a 0.2% fatality rate
    • Schools in Japan have been closed for one month as of March 2nd through April 2020 [xxxiii]
    • China and Hong Kong have also closed schools
  • Geriatrics
    • Elderly patients appear to have the greatest risk of complications and mortality
    • 50-59 y/o has 1.3% mortality
    • 60-69 y/o has 3.6% mortality
    • 70-79 y/o has 8% mortality
    • 80 and above y/o has 14.8% mortality
    • The US has a population aged over 65 of 49.2 million in 2016[xxxiv]
    • The US has 12.6 million people over the Age of 80[xxxv]
  • Pregnancy[xxxvi]
    • Currently there is no published scientific reports about susceptibility of pregnant women to COVID-19
    • Pregnant women experience immunologic and physiologic changes which might make them more susceptible to viral respiratory infections
    • Pregnant women also might be at risk for severe illness, morbidity, or mortality compared to the general population as observed in cases of other related coronavirus infections
    • There is currently no data on breastfeeding and communication of COVID-19 via breastmilk
    • In limited studies on women with COVID-19 and another coronavirus infection, Severe Acute Respiratory Syndrome (SARS-CoV), the virus has not been detected in breast milk

Infection Control and Prevention

  • The best way to prevent the virus is to avoid being exposed[xxxvii]
  • Stay away from sick people
  • Avoid touching your eyes, noes and mouth
  • Cover your cough and sneezes, throw tissues into the trash
  • Clean frequently touched surfaces (door knobs, counter tops, banisters) with a common household cleaning spray or wipe.
  • Handwashing with soap and water for 20 seconds or alcohol (60%) based hand sanitizers
  • There are current efforts for vaccine creation and prophylactic medications (see below)
  • The virus is spread via respiratory droplets from nose of mouth of infected people[xxxviii]
  • Droplets can land on surfaces
  • Other people can touch these surfaces and infect themselves by touching their face, eyes, nose or mouth
  • Healthy people in the general public have no benefit from wearing masks[xxxix]
  • Infection control for healthcare workers[xl]
  • Take steps to ensure all persons with symptoms of suspected COVID-19 or other respiratory infection (e.g., fever, cough) adhere to respiratory hygiene and cough etiquette, hand hygiene, and triage procedures throughout the duration of the visit.
  • Ensure that patients with symptoms of suspected COVID-19 or other respiratory infection (e.g., fever, cough) are not allowed to wait among other patients seeking care.  Identify a separate, well-ventilated space that allows waiting patients to be separated by 6 or more feet, with easy access to respiratory hygiene supplies.
  • Identify patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility.
  • Inform infection prevention and control services, local and state public health authorities, and other healthcare facility staff as appropriate about the presence of a person under investigation for COVID-19
  • Place a patient with known or suspected COVID-19 in an Airborne infection isolation room (AIIR) that has been constructed and maintained in accordance with current guidelines.
  • AIIRs are single patient rooms at negative pressure relative to the surrounding areas, and with a minimum of 6 air changes per hour (12 air changes per hour are recommended for new construction or renovation). Air from these rooms should be exhausted directly to the outside or be filtered through a high-efficiency particulate air (HEPA) filter before recirculation. Room doors should be kept closed except when entering or leaving the room, and entry and exit should be minimized. Facilities should monitor and document the proper negative-pressure function of these rooms.
  • If an AIIR is not available, patients who require hospitalization should be transferred as soon as is feasible to a facility where an AIIR is available. If the patient does not require hospitalization they can be discharged to home (in consultation with state or local public health authorities) if deemed medically and socially appropriate. Pending transfer or discharge, place a facemask on the patient and isolate him/her in an examination room with the door closed. Ideally, the patient should not be placed in any room where room exhaust is recirculated within the building without HEPA filtration.
  • Once in an AIIR, the patient’s facemask may be removed. Limit transport and movement of the patient outside of the AIIR to medically-essential purposes. When not in an AIIR (e.g., during transport or if an AIIR is not available), patients should wear a facemask to contain secretions.
    • Facilities should keep a log of all persons who care for or enter the rooms or care area of these patients.
  • Gloves
    • Perform hand hygiene, then put on clean, non-sterile gloves upon entry into the patient room or care area. Change gloves if they become torn or heavily contaminated.
    • Remove and discard gloves when leaving the patient room or care area, and immediately perform hand hygiene.
  • Gowns
    • Put on a clean isolation gown upon entry into the patient room or area. Change the gown if it becomes soiled. Remove and discard the gown in a dedicated container for waste or linen before leaving the patient room or care area. Disposable gowns should be discarded after use. Cloth gowns should be laundered after each use.
  • Respiratory Protection
    • Use respiratory protection (i.e., a respirator) that is at least as protective as a fit-tested NIOSH-certified disposable N95 filtering facepiece respirator before entry into the patient room or care area. See appendix for respirator definition.
    • Disposable respirators should be removed and discarded after exiting the patient’s room or care area and closing the door. Perform hand hygiene after discarding the respirator.
    • If reusable respirators (e.g., powered air purifying respirator/PAPR) are used, they must be cleaned and disinfected according to manufacturer’s reprocessing instructions prior to re-use.
    • Respirator use must be in the context of a complete respiratory protection program in accordance with Occupational Safety and Health Administration (OSHA) Respiratory Protection standard (29 CFR 1910.134external icon). Staff should be medically cleared and fit-tested if using respirators with tight-fitting facepieces (e.g., a NIOSH-certified disposable N95) and trained in the proper use of respirators, safe removal and disposal, and medical contraindications to respirator use.
  • Eye Protection
    • Put on eye protection (e.g., goggles, a disposable face shield that covers the front and sides of the face) upon entry to the patient room or care area. Remove eye protection before leaving the patient room or care area. Reusable eye protection (e.g., goggles) must be cleaned and disinfected according to manufacturer’s reprocessing instructions prior to re-use.  Disposable eye protection should be discarded after use.
  • Healthcare workers should revisit their procedures for donning, doffing and disposing their PPE[xli]
  • Assume every person is potentially infected or colonized with a pathogen that could be transmitted in the health care setting.
  • Strict contact, airborne and eye protection should be used for healthcare workers

 

 

Emerging Treatments

  • Chloroquine[xlii]
    • Antimalarial and autoimmune medicine
    • Commonly found as an oral tablet
    • Antiviral properties and immunomodulating effects
    • Currently in FDA phase 3 study [xliii]
      • 400mg by mouth, daily for 5 days
    • One study appears to advocate a 1gm loading dose followed by 500mg BiD[xliv]
      • There are questions on duration of treatment with this regime
    • Remdesivir study[xlv]
      • Developed by Gilead Sciences
      • Investigational broad-spectrum antiviral treatment previously trialed against Ebola
      • Shows good efficacy against MERS and SARS in animal studies[xlvi]
      • 200mg IV on day one then 100mg daily for a total of 10 days [xlvii]
        • University of Nebraska Medical Center study
      • Oseltamivir
        • Influenza A and B treatment
        • Currently under investigation
        • 75mg by mouth, twice per day for 5 days
      • Ribavirin
        • Hepatitis C antiviral treatment
        • 1200mg twice per day
      • Lopinavir/Ritonavir
        • HIV antiviral treatment
        • 400mg/100mg by mouth twice per day
        • Brand name Kaletra

 

Vaccine Development

  • Multiple laboratories are working on vaccines
  • Promising trials from Hong Kong [xlviii]
  • Moderna Theraputics from Massachusetts[xlix]
  • Novavax announced on 2/26/20 it has started testing COVID-19 vaccine candidates in animal models in the hopes of identifying a candidate to be used in human testing as early as this spring[l]

 

Public Health Aspect

Summary

  • Case fatality rate of 2.3% globally
  • As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China in 56 countries
  • There have been 2,462 associated deaths worldwide
  • Declared a public health emergency by Health and Human Services HHS on January 31, 2020. [li]
  • Medically fragile patients with pre-existing conditions including lung disease, poorly controlled diabetes and cardiac disease are at increased risk for complications
  • Elderly patients are at increased risk
    • 50-59 y/o has 1.3% mortality
    • 60-69 y/o has 3.6% mortality
    • 70-79 y/o has 8% mortality
    • 80 and above y/o has 14.8% mortality
  • SARS-CoV-2 has a R0 of 2.5
    • Measles has an R0 value of approximately 12-18 in unvaccinated people
    • Seasonal influenza has an R0 of 1.2
  • There is concern for the ability to have a second re-infection after the initial infection has cleared[lii]

 

Cases and Epidemiology by Geography

  • March 7th, 2020[liii]
    • Global cases 105,559
      • Deaths 3,555
      • Recovered 58,354
    • China 80,652 cases
      • 2,959 deaths in Hubei, China
    • South Korea 7,041 cases
      • 44 deaths in South Korea
    • Italy 5,883 cases
      • 233 deaths in Italy
    • Iran 5,823 cases
      • 145 deaths in Iran
    • Germany 799 cases
    • France 716 cases
      • 11 deaths in France
    • Spain 500 cases
      • 10 deaths in Spain
    • Japan 461 cases
      • 6 deaths in Japan
    • USA 376 cases
      • 12 deaths in King County, Washington
    • Switzerland 268 cases
    • UK 206 cases
    • Netherlands 188 cases
    • Belgium 169 cases
    • Sweden 161 cases
    • Norway 147 cases
    • Singapore 138 cases
    • Hong Kong 108 cases
    • Malaysia 93 cases
    • Bahrain 85 cases
    • Austria 79 cases
    • Australia 63 cases
    • Kuwait 61 cases
    • Canada 54 cases
    • 54 cases in Iraq
      • 4 deaths in Iraq
    • Thailand 50 cases
    • Iceland 50 cases
    • Greece 46 cases
    • United Arab Emirates 45 cases
    • Taiwan 45 cases
    • India 34 cases
    • San Marino 23 cases
    • Denmark 23 cases
    • Lebanon 22 cases
    • Palestine 22 cases
    • Israel 21 cases
    • Portugal 20 cases
    • Czech Republic 19 cases
    • Vietnam 18 cases
    • Ireland 18 cases
  • North America
    • See appendix
  • South America
    • See appendix
  • Asia
    • See appendix
  • Europe
    • See appendix
  • Africa
    • See appendix
  • Australia/Pacific
    • See appendix
  • Most commonly effected age
    • Eighty-seven percent of patients were aged 30 to 79 years (38,680 cases)[liv]
  • Vulnerable populations
  • Medically fragile patients with pre-existing conditions including lung disease, poorly controlled diabetes and cardiac disease are at increased risk for complications[lv]
  • Elderly patients are at increased risk

 

 

Communicability and Transmission

  • R0 (R naught) is the basic reproduction number and predicts how many people one infected person spread the disease to another person[lvi]
    • R0 means the disease will likely die out on its own. One sick person usually does not infected another person, or less than one person.
    • R1 means that one sick person infects at least one other person
    • Measles has an R0 value of approximately 12-18 in unvaccinated people
    • Seasonal influenza has an R0 of 1.2
    • Smallpox R0 is 7
    • SARS-CoV-2 has a R0 of 2.5
  • There is concern for the ability to have a second infection after the initial infection has passed[lvii]
  • Contact transmission (fomite to face)
    • A patient with COVID19 coughs and large droplets containing virus particles spread outward
    • These droplets settle on surfaces in a room, creating a thin film of the virus
      • Virus particles may be shed in other body fluids including
        • Sputum
        • Nasal secretions
        • Stool
        • Saliva
        • Urine
        • Blood
      • Most human coronavirus particles can survive for approximately 1 week on surfaces[lviii]
        • Animal coronavirus can persist for weeks or months on inanimate surfaces
      • Virus particles persist on fomites in the environment
      • An un-infected person touches the contaminated surface hours or even days later
      • The uninfected person then touches their nose or mouth, transmitting the infection
      • Regular cleansing of environmental surfaces prohibits spread
        • 70% ethanol
        • 5% sodium hypochlorite solution (bleach)
      • Handwashing and/or high concentration ethanol neutralizes the virus

 

Case Fatality Rates

  • Age[lix]
    • 0-9 y/o has no deaths reported as of yet
    • 10-19 y/o has 0.2% mortality
    • 20-29 y/o has 0.2% mortality
    • 30-39 y/o has 0.2% mortality
    • 40-49 y/o has 0.4% mortality
    • 50-59 y/o has 1.3% mortality
    • 60-69 y/o has 3.6% mortality
    • 70-79 y/o has 8% mortality
    • 80 and above y/o has 14.8% mortality
  • Sex
    • In one study of 425 patients with pneumonia and confirmed COVID-19, 57% were male.
  • Comorbidities
    • Medically fragile patients with pre-existing conditions including lung disease, poorly controlled diabetes and cardiac disease are at increased risk for complications[lx]

 

Comparison to Other Major Viruses41

  • Ebola
    • Identified 1976
    • 33,5577 cases
    • 13,562 deaths with fatality rate of 40.4%
    • 9 countries
  • Nipah
    • Identified in 1998
    • 513 cases
    • 398 deaths with fatality rate of 77.6%
    • 2 countries
  • SARS
    • Identified in 2002
    • 8,096 cases
    • 774 deaths with fatality rate of 9.6%
    • 29 countries
  • MERS
    • Identified in 2012
    • 2,494 cases
    • 858 deaths with fatality rate of 34.4%
    • 28 countries
  • COVID-19
    • Identified in 2020
    • 83,774 cases
    • 2,867 deaths with fatality rate of 3.4%
    • 56 countries

 

Social Impact

 

Summary

  • There will be a marked decrease in gatherings
    • Concerts
    • Sporting events
    • Movie theaters
    • Church
    • School
    • Parties
  • School Closures
    • The closure of schools results in an additional 10–15% drop in infections after individuals have modified their behavior.
    • Ability to study online or at home needs to be evaluated[lxi]
    • Children at home will be an issue for working parents and childcare concerns
  • Targeted Public Health Community Messaging Decreases Community Spread
    • Behavior modification alone drops the total income loss by 62% compared to the base case44
    • “In light of our results, we believe that activities such as governmental policies and media campaigns that urge the public to modify their behavior in order to reduce exposure to an infectious disease are likely to greatly reduce epidemic attack rates.”44

 

Politeness vs. Protection

  • Decreased shaking hands, kissing and physical contact with acquaintances
  • Wuhan Foot bump for greeting

 

Mass Gatherings

  • Expect people to avoid crowds and large gatherings

 

Special Events

  • Potential changing dates or cancelling Olympics in Japan, later in 2020
  • Closure of UAE cycling race
  • Closure of climbing competitions
  • Sporting events being pushed back

 

Personal Space and Distance

  • 2 meter “personal space”
  • Decrease in handshaking and personal contact

 

Workplace Interactions

  • Attempts to keep personal space
  • Decreased handshaking
  • Do not stigmatize of poke fun at colleagues afraid of touching or being close

 

Social Interactions

  • Decreased gatherings, parties and attendance of churches, schools

School Closures

  • “We find that closing schools mitigates an epidemic better than the provision of antiviral kits. The governmental actions of school closure are more effective although less economically efficient in preventing infections than the distribution of antiviral kits.”44
  • Closing schools (CS) is the second largest single factor in reducing the income loss and epidemic size (modified individual behavior is the largest factor). Under the CS strategy, the income loss due to care taking (of sick children) drops by 93% and the income loss due to illness drops by 75% compared to the base case. The epidemic size is lowered by 87,237 or 78% compared to the base case.44
  • Closing schools results in fewer number of sick children and sick adults, and hence lower productivity and income loss due to sickness. Our results show that more children fall sick when schools are open, and more working adults have to stay home to take care of the sick children. Keeping schools open results in more than $4 million in indirect income loss whereas CS results in less than $1 million in indirect income loss. However, closing schools, results in much higher cost of disease avoidance ($18 million) because many working adults have to forgo work and stay home with children. 44
  • The Economic Impact of Pandemic Influenza in the United States: Priorities for Intervention[lxii]

 

Business Impact

 

Summary

  • Expect disruptions to supply chains
  • Expect great disruptions to medication and medical device supply chains
    • Medication and medical device shortages
  • Expect workforce and labor disruptions
    • Healthcare workers will likely be hardest hit
    • Preparedness with a company pandemic plan is important
    • Changes in commerce will occur
      • How, when and where consumers source items
    • Resource poor countries should expect a greater impact of illness and shortages
    • Emerging markets
      • Home entertainment
      • Personal hygiene and cleaning products
    • Declining markets
      • Business involving people gathering

Supply Chain Disruption

  • Human medicines[lxiii]
    • Expect interruptions and shortages of critical medicines
    • FDA has been communicating with >180 manufacturers to ask for evaluation of their supply chains and components manufactured in China
    • Approximately 20 drugs are solely sourcing their active pharmaceutical ingredients from China
  • Medical Devices46
    • FDA is aware of 63 manufacturers representing 72 facilities in China that produce essential medical devices
    • Expect shortages on Personal protective equipment (PPE) such as surgical gowns, gloves masks and respirators
  • Biologics and Blood Supply46
    • The FDA is not aware of any cellular or gene therapies made in China for the US market
    • The potential for transmission of COVID-19 by blood and blood components is unknown at this time
    • Respiratory viruses are not known to be transmitted by blood transfusion
  • Food46
    • The FDA is unaware of any reports, at the time of writing, of human illness that suggests COVID-19 can be transmitted by food or food packaging
  • Animal medicines46
    • There are 32 animal drug firms that make finished drugs or source active pharmaceutical ingredients in China for the US> All 32 firms have been contacted and no shortages have been reported at this time.
      • Six of these firms are seeing disruptions in supply chain and that could soon lead to shortages
    • Additional Resources and Strategies46
      • Lengthen expiration dates to mitigate human drug shortages
      • Improve critical infrastructure by requiring risk management plans
        • Requirement of certain drug manufacturers to conduct risk assessments to identify vulnerabilities in manufacturing supply chain
      • Improve critical infrastructure through data sharing and more accurate supply chain information
      • Establish reporting requirements for device manufacturers

 

Workforce Disruption

  • Healthcare workers[lxiv]
    • Studies out of Wuhan, China show that healthcare workers make up 3.8% of those confirmed infections
    • 63% of healthcare workers in Wuhan, China tested positive
    • 8% of healthcare workers infected were classified as severe or critical
  • Workplace personnel preparation[lxv]
    • Studies and recommendations from OSHA Influenza pandemic plans
    • A pandemic could effect as much as 40% of workforce
      • Employees can be absent for a variety of reasons
      • The employee is sick, themselves
      • Care for sick family members
      • Care for children with closed schools
      • Employees are afraid of getting sick
      • Employee has died and employer has not been notified
    • Changes in patterns of commerce[lxvi]
      • Consumer demand for infection control items and medications increase dramatically
      • Consumer interest in other items will decline
      • Consumers may change shopping times
        • Shopping at off-peak hours to avoid contact with other people
        • Increased interest in home delivery
        • Increased interest in drive-through locations
      • Staggering of employee shifts
        • Assign employees into groups A and B
        • Group A works 0600 to 1300
        • Group B works 1330 to 2030
      • Employee work spaces
        • Provide a workspace of at least 2.5 square meters[lxvii]
        • Have employees keep a two meter distance between themselves and others in the office
        • Keep elevators at less than half-full
        • Wipe down surfaces including phones, keyboards, desk surfaces, drawer handles
        • When possible do not have employee workstations directly across from others
        • Each workstation has wipes and hand sanitizer
        • Take employee temperatures daily
      • Employee behaviors
        • Suspend business travel
        • Encourage sick workers to stat home
        • Relax work-excuse note requirements
        • Ensure employees know access points for medical services
        • Febrile workers should remain at home for up to 10 days after fever has subsided
        • Encourage employees to monitor reliable news sources

Tele-Commuting[lxviii]

  • Encourage work from home or telecommute options

 

Food Security

  • Sick food service workers
  • Sick food store workers
  • Interrupted supply chains

 

Loss of Maintenance Services

  • Machinery repair services will experience labor interruptions
  • Disruption of parts supply chain

 

Emerging Markets

  • Home entertainment
    • Video streaming services
    • Video game subscription services
  • Home delivery services

 

Declining Markets

  • Events with large public gatherings
    • Concerts
    • Sports events
    • Restaurants
    • Schools
    • Travel

 

Resource Poor Countries

  • Resource poor countries will likely have a higher rate of death due to COVID19

Environmental Impact

 

Summary

  • Currently there is no evidence that domestic animals or pets can transmit the COVID-19 virus
  • Disruptions to waste management services can be expected
  • COVID-19 will likely become a seasonal and globally circulating virus

 

Animal Infections[lxix]

  • Animals and domestic pets can test positive for the COVID 19 virus[lxx]
    • This is currently of unclear clinical significance and developing
  • There is question if the animals actually are clinically ill themselves
  • Currently there is no evidence that domestic animals or pets can transmit the COVID-19 virus
  • Currently there is no evidence that domestic animals or pets can become infected with the COIVD-19 virus

 

Waste Management and Processing

  • Disruptions to waste management services can be expected
  • Household trash collection

 

Seasonality of Viral Infections

  • COVID-19 will likely become a seasonal and globally circulating virus

 

 

 

 

 

 

 

 

 

 

 

 

 

APPENDIX A

COVID 19 PREPARATIONS and GOALS

 

Timeline of Actions

Initial Planning Stages

  • Dedicate at least 1 FT emergency manager per facility or organization
  • Dedicate at least 1 FT infection control director (education, training, monitoring, exercises)
  • Designate chain of command and ORG structure for emergency manager and infection control
  • Create pandemic preparedness committee with members of each department
  • Ensure communication plans and access for preparedness committee are in place and regular contact is established (daily review calls)
  • Participate in local community planning teams with EMS, other facilities and Police
  • Prepare telephone and web-based advice lines for unnecessary visit reduction

 

Initial Targets

  • Be ready to convert 30-40% of licensed bed capacity for COVID19 patients
    • 10-20% of facility capacity can be opened by
      • expediting discharges
      • converting single rooms to double rooms
      • opening closed areas
      • conversion of flat spaces such as lobbies, waiting rooms and classrooms
      • Establish teamwork with regional planners for additional bed space up to 200% of capacity in 2 weeks
      • Stockpile 3 weeks worth of simple surgical masks
        • Mask all patients and visitors entering the facility
      • Ensure clinical staff are familiar with CDC guidance on infection control
      • Powered air-purifying respirators (PAPRs) for high risk procedures

 

Cohorting Patients in Hospital Plan

  • Screen patient for possible COVID19 or other respiratory pathogens
    • Group one is for patients with positive COVID 19
    • Group two is for patients with pending test results but clinical suggestion of COVID19
    • Group three is for negative tests or those with inconsistent clinical significance

 

Preparing Staff and Volumes of Patients

  • Vaccinate all staff for influenza to reduce potential burden of this illness
  • Organize in-home childcare for healthcare workers’ family
  • Provide medical daycare for sick family members of clinical staff
  • Communicate with transparency and ally fear
  • Shift clinical staff from closed areas or lower volume areas
    • Deploy “just in time education” and buddy system
  • Augment clinical staff with non-traditional personnel
    • Medical staff with prior clinical experience
      • Administration, research, retirees
    • Related medical staff
      • Dentists, veterinarians, EMS
      • Non-clinical staff within the facility
      • Non-clinical staff outside the hospital
    • Prepare training modules for incoming surge capacity staff

 

Prepare for Allocation of Resources

  • Plan to defer non-essential and elective services
    • Continually review which services can be reduced
  • Normal staffing rations will not be able to be maintained
  • Plan for alternative sites to provide ICU level services
    • Cath labs
    • Operating rooms
    • PACU
    • Endoscopy
  • Create clinical guidelines for use or denial of resource intensive services
  • Develop robust triage procedures for patients competing for limited resources
    • Early admission
    • Early discharge
    • Life support
  • Mobilize and ensure access to web-based advice lines for reduction of unnecessary visits

 

Hospital costs expected[lxxi]

  • A 164 bed hospital will require at least $1,000,000 (2006 dollars) in funding to properly and effectively prepare for an outbreak
    • $200,000 for basic pandemic healthcare plan
    • $160,000 for providing staff and medical professionals with proper education and tools necessary to identify and asses patients
    • $400,000 to stockpile PPE
    • $240,000 for help stockpiling additional tools, equipment and supplies

 

 

Sample Ed Triage Concepts

  • Establish triage centers outside of emergency departments
    • Parking lots
    • Offsite locations
  • These triage centers are staffed with nurses to handle swabbing and clerking
    • Initial screening swab for illness
    • Collection of patient demographic information

Patient Flow in Triage Centers

  • Patient calls for appointment to be seen at screening center
  • Patient is stratified according to CDC criteria
  • Pt is booked into appointment slot at triage center
  • Pt is swabbed and screened in triage
    • Patients reviewed by triage doctor
    • Stable patients are told to self-isolate and await results
    • Unstable patients are not sent to ED
    • Unstable patients are sent to designated areas within facility for COVID19 resus
      • Adjacent room to ED
        • Stocked with easily cleanable surfaces type furniture
        • Portable CXR
        • Airway kit
        • Crash cart
        • ACLS medications
      • Consider establishing community response teams that can go to patient homes for swabbing

 

 

Response interventions

 

Anticipation

  • First stage of response
  • Emergency cannot be predicted but it can be anticipated
  • Anticipation focuses on most likely threats
  • Encompasses forecasting most likely diseases to emerge and quick identification of the drivers that will worsen the impact
  • A variety of scenarios should be explored to allow a reactive response to the unexpected

 

Early Detection

  • Epidemics require investigation into their sources and at the same time require rapid-containment measures
  • New diseases require new interventions
  • Flexibility and development of new management tools, proactive risk assessment and constant vigilance are needed.
  • Early detection allows the rapid implementation of containment measures
  • Early detection begins at the health care setting
  • Health care workers must be trained and empowered to
    • recognize potential epidemic disease
    • report quickly an unusual event
    • Reduce the risk of community transmission by isolating severely-ill patients
    • Prevent household transmission by protecting health care givers at home
    • Reduce the mortality rate
    • Know how to protect themselves and employ infection prevention and control measures and how to avoid outbreaks amplified in health care facilities
  • Early laboratory confirmation is essential
    • When this cannot be done at country level, the affected entities must be confident they can count on the support of a network of more sophisticated regional laboratories
    • It is critically important for public health security that there is a system for safely taking samples and shipping specimens to relevant laboratories in full compliance with biosafety and biosecurity regulations

 

Containment

  • Effective and rapid containment of emerging diseases is just as vital as early detection
  • Rapid containment should start as soon as the first case is detected
  • It requires skilled professionals to safely implement the necessary countermeasures
  • Pre-training of these professionals is essential to guarantee the safety and efficiency of the operations.

 

Control and Mitigation

  • Once the infectious disease threat reaches an epidemic or pandemic level, the goal of the response is to
    • mitigate its impact
    • reduce its incidence, morbidity and mortality with human life
    • reduce disruptions to economic, political, and social systems

 

Elimination or Eradication

  • Control of a disease may lead to its elimination or eradication
    • Elimination means that the disease is no longer considered as a major public health issue.
      • Intervention measures (surveillance and control) should continue to prevent its re-emergence.
    • Eradication of a disease is much more difficult and rarely achieved
      • This involves the permanent elimination of its incidence worldwide
      • There is no longer a need for interventions measures
      • Three criteria need to be met in order to eradicate a disease
        • there must be an available intervention to interrupt its transmission
        • there must be available efficient diagnostic tools to detect cases that could lead to transmission
        • humans must be the only reservoir.

 

 

Four Main Response Teams and Goals

 

Coordinating Responders

  • What are the characteristics of the event that describe it as a crisis?
    • Health aspects effected
    • Socio-economic areas of impact
  • Who are the people, groups and organizations who should work for the response?
    • Available resources
    • Team selection and allocation of resources
    • Organizational chart
  • What should they do?
    • Assign tasks and functions
    • Commander’s briefing
  • Where can responders meet?
    • emergency operation center or command post
  • How do they share information?
    • share point
    • telephone numbers
    • generic email

 

Health Information

  • Surveillance of the disease
    • Is there a case definition shared by all stakeholders?
    • Which laboratories are involved in the testing /confirmation of cases and deaths, and where are they situated?
    • Is there an updated epidemiological curve and mapping of cases and deaths?
    • Which are the risk groups, by gender and age?
  • Interventions
    • What is the target population?
    • What material and human resources are needed and how much?
    • What are the indicators of success?
      • vaccine coverage
      • households targeted
      • number of people treated
      • reduction in spread by X percent
      • reduction in mortality by x percent

 

Communicating Risk and Controlling “Infodemics”

  • An “Infodemic” is the uncontrolled spread of rumours, gossip and unreliable information within a nervous population
  • Infodemics, like epidemics, can be managed
    • successful management of infodemics will be based on
      • monitoring and identifying
      • analysis
      • control and mitigation measures
    • Has the situation been well analyzed in terms of audience, sources and specificity of the context?
    • Are tools in place in place to monitor an infodemic? Is monitoring reactive and adaptable enough?
    • Has translational communication taken place (to transform scientific information into lay language and format)?
    • Are the communication channels (and messengers) adequate, effective and acceptable to communities? (culturally, cost-effectively)?
    • Is there a plan to communicate regularly with the various audiences?
    • Have all personnel and volunteers in the risk communication response been trained in risk communication approaches, and consistent messaging?

 

Health Interventions

  • What are the key interventions needed to control the outbreak at this stage of the event?
  • Who should implement them?
  • How is the impact measured on morbidity, mortality, transmission, and whole of society?

 

 

Basic Concepts

 

Grading the Severity of Impact

  • Serious
    • Complete loss of service or output
  • Major
    • Major loss of agency / service to users
  • Moderate
    • Disruption to users due to agency problems
  • Minor
    • Reduced efficiency or disruption to agency working
  • Minimum
    • No loss of service

 

Epidemic Phases

  • Introduction or Emergence
  • Localized transmission
  • Amplification
  • Reduced transmission

 

Field Epidemiology

  • It encompasses three main areas
    • monitoring and identifying health threats
    • outbreaks investigation
    • actions for mitigation and control

[i] https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

[ii] https://mailchi.mp/esicm/the-future-of-haemodynamic-monitoring-first-webinar-of-the-year-1009715

[iii] https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it

[iv] https://www.ncbi.nlm.nih.gov/pubmed/15141377

[v] https://www.who.int/health-topics/coronavirus

[vi] https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html

[vii] https://www.pharmaceutical-technology.com/news/coronavirus-incubation-period-27-days/

[viii] https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463?searchresult=1

[ix] http://virological.org/t/response-to-on-the-origin-and-continuing-evolution-of-sars-cov-2/418

[x] https://www.who.int/emergencies/mers-cov/en/

[xi] https://www.cdc.gov/coronavirus/mers/index.html

[xii] https://www.who.int/ith/diseases/sars/en/

[xiii] https://www.who.int/csr/sars/en/WHOconsensus.pdf

[xiv] https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html

[xv] https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

[xvi] https://pubs.rsna.org/doi/10.1148/radiol.2020200463

[xvii] https://mailchi.mp/esicm/the-future-of-haemodynamic-monitoring-first-webinar-of-the-year-1009715

[xviii] EM-Crit COVID19 guidelines march 2, 2020

[xix] https://jamanetwork.com/journals/jama/fullarticle/2762688

[xx] EM-Crit COVID19 guidelines march 2, 2020

[xxi] https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html

[xxii] https://www.cdc.gov/coronavirus/2019-ncov/about/testing.html

[xxiii] http://www.cidrap.umn.edu/news-perspective/2020/02/feds-allow-state-public-health-labs-test-covid-19

[xxiv] https://www.worldometers.info/coronavirus/covid-19-testing/

[xxv] https://www.worldometers.info/coronavirus/covid-19-testing/

[xxvi] https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html

[xxvii] https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

[xxviii] https://emcrit.org/pulmcrit/sepsis-hlh-overlap-syndrome-shlhos/

[xxix] https://www.dynamed.com/condition/covid-19-novel-coronavirus

[xxx] https://www.dynamed.com/condition/covid-19-novel-coronavirus

[xxxi] https://www.dynamed.com/condition/covid-19-novel-coronavirus

[xxxii] https://jamanetwork.com/journals/jama/fullarticle/2762130

[xxxiii] https://www.bbc.com/news/world-asia-51663182

[xxxiv] https://acl.gov/sites/default/files/Aging%20and%20Disability%20in%20America/2017OlderAmericansProfile.pdf

[xxxv] https://medium.com/@amwren/forget-about-the-death-rate-this-is-why-you-should-be-worried-about-the-coronavirus-890fbf9c4de6

[xxxvi] https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/pregnancy-faq.html

[xxxvii] https://www.cdc.gov/coronavirus/2019-ncov/about/symptoms.html

[xxxviii] https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

[xxxix] https://www.ama-assn.org/delivering-care/public-health/covid-19-6-key-points-physicians-should-share-patients

[xl] https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.html

[xli] https://www.ama-assn.org/delivering-care/public-health/8-ways-protect-doctors-caring-patients-covid-19

[xlii] https://www.nature.com/articles/s41422-020-0282-0

[xliii] https://clinicaltrials.gov/ct2/show/NCT04261517

[xliv] https://www.sciencedirect.com/science/article/pii/S0924857920300820

[xlv] https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins

[xlvi] https://www.niaid.nih.gov/news-events/remdesivir-prevents-mers-coronavirus-disease-monkeys

[xlvii] https://www.pulmonologyadvisor.com/home/topics/lung-infection/clinical-trials-underway-to-test-remdesivir-for-covid-19/

[xlviii] https://www.sciencedaily.com/releases/2020/02/200226091227.htm

[xlix] https://time.com/5790545/first-covid-19-vaccine/

[l] http://ir.novavax.com/news-releases/news-release-details/novavax-advances-development-novel-covid-19-vaccine

[li] https://www.cdc.gov/coronavirus/2019-ncov/about/testing.html

[lii] https://news.sky.com/story/coronavirus-japan-confirms-first-case-of-person-being-reinfected-with-covid-19-11944295

[liii] https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

[liv] http://www.cidrap.umn.edu/news-perspective/2020/02/study-72000-covid-19-patients-finds-23-death-rate

[lv] https://www.medscape.com/viewarticle/925681

[lvi] https://www.popsci.com/story/health/how-diseases-spread/

[lvii] https://news.sky.com/story/coronavirus-japan-confirms-first-case-of-person-being-reinfected-with-covid-19-11944295

[lviii] https://www.ncbi.nlm.nih.gov/pubmed/32035997

[lix] https://www.businessinsider.com/coronavirus-death-age-older-people-higher-risk-2020-2

[lx] https://www.medscape.com/viewarticle/925681

[lxi] Network Dynamics and Simulation Science Laboratory, Virginia Bioinformatics Institute, 1880 Pratt Drive, Bldg. XV, Virginia Tech, Blacksburg, VA 24061, Chris Barrett,* Keith Bisset,* Jonathan Leidig,* Achla Marathe,* and Madhav Marathe* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039122/

[lxii]Meltzer MI, Cox NJ, Fukuda K. The Economic Impact of Pandemic Influenza in the United States: Priorities for Intervention. Emerging Infectious Diseases. 1999;5(5):659-671. doi:10.3201/eid0505.990507.

[lxiii] https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-supply-chain-update

[lxiv] https://jamanetwork.com/journals/jama/fullarticle/2762130

[lxv] https://www.osha.gov/Publications/influenza_pandemic.html

[lxvi] https://www.osha.gov/Publications/influenza_pandemic.html

[lxvii] https://qz.com/work/1809121/beijings-10-rules-for-curbing-coronavirus-in-the-workplace/

[lxviii] https://www.reuters.com/article/us-china-health-japan/japan-urges-firms-to-have-staff-work-from-home-over-coronavirus-soccer-postponed-idUSKCN20J0EB

[lxix] https://www.oie.int/en/scientific-expertise/specific-information-and-recommendations/questions-and-answers-on-2019novel-coronavirus/

[lxx] https://www.usatoday.com/story/news/nation/2020/02/28/coronavirus-dogs-covid-test-positive-hong-kong-patient-pet/4903014002/

[lxxi] 2006 report named “Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science”

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