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 7^th 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 3^rd 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 27^th, 2020
  - United States
    - 445 concluded tests
    - 14 positives
    - 1% positivity
    - March 2^nd 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 2^nd 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”

Clinical Aspect

Summary

Virus Family and Genealogy

Signs and Symptoms

Stages of Illness

Testing and Guidelines

Treatment Guidelines

Special Populations

Infection Control and Prevention

Emerging Treatments

Vaccine Development

Public Health Aspect

Summary

Cases and Epidemiology by Geography

Communicability and Transmission

Case Fatality Rates

Comparison to Other Major Viruses41

Social Impact

Summary

Politeness vs. Protection

Mass Gatherings

Special Events

Personal Space and Distance

Workplace Interactions

Social Interactions

School Closures

Business Impact

Summary

Supply Chain Disruption

Workforce Disruption

Tele-Commuting[lxviii]

Food Security

Loss of Maintenance Services

Emerging Markets

Declining Markets

Resource Poor Countries

Environmental Impact

Summary

Animal Infections[lxix]

Waste Management and Processing

Seasonality of Viral Infections

APPENDIX A

Initial Planning Stages

Initial Targets

Cohorting Patients in Hospital Plan

Preparing Staff and Volumes of Patients

Prepare for Allocation of Resources

Hospital costs expected[lxxi]

Sample Ed Triage Concepts

Patient Flow in Triage Centers

Response interventions

Anticipation

Early Detection

Containment

Control and Mitigation

Elimination or Eradication

Four Main Response Teams and Goals

Coordinating Responders

Health Information

Communicating Risk and Controlling “Infodemics”

Health Interventions

Basic Concepts

Grading the Severity of Impact

Epidemic Phases

Field Epidemiology

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