Coronavirus disease 2019

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Coronavirus replication cycle

Novel coronvavirus disease, also called COVID-19 (COrona VIrus Disease 19), is a viral disease outbreak that was first reported from Wuhan, China and is caused by a type of Coronavirus called SARS-Cov-2(Severe Acute Respiratory Syndrome, coronavirus-2).

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Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maryland, Massachusetts, Missouri, New Jersey,  New York, North Carolina, Ohio,  Pennsylvania, Puerto Rico, Rhode Island, South Carolina, Texas, and Utah.

Single dose vaccine

CVS is now offering the new Johnson and Johnson's (Jenssen) vaccine in many states in the United States. Here is how to register. Choose your state according to where you reside and or work.

• CVS COVID single dose vaccine finder available in many states.

Causative organism

COVID-19 is caused by a type of coronavirus called SARS-Cov-2.

Spread

The disease spreads primary through droplets of people that are infected via droplets that can contaminate any surface that an infected person touches such as doorknobs, countertops, handrails, and any other surface an infected person touches as well as via aerosol droplets when an infected person coughs or sneezes.

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Is COVID-19 like a flu?

Infectivity

The virus that causes coronavirus disease 2019 (COVID-19) is stable for several hours to days in aerosols and on surfaces, according to a new study from National Institutes of Health, CDC, UCLA and Princeton University scientists in The New England Journal of Medicine. The scientists found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel. The results provide key information about the stability of SARS-CoV-2, which causes COVID-19 disease, and suggests that people may acquire the virus through the air and after touching contaminated objects.

Symptoms

According to the Centers for Disease Control (CDC), the symptoms include the following:

• Fever
• Cough
• Shortness of breath
• Chest pain or pressure in the chest
• confusion or inability to arouse
• Bluish lips or face called cyanosis

• This list is not all inclusive. Please consult your medical provider for any other symptoms that are severe or concerning.

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Symptoms of COVID-19

Pathophysiology

The infection transmits from person to person via droplets and contact. It can also be transmitted to cats.

Infectious dose

• The human infectious dose of SARSCoV-2, which causes coronavirus disease 19 (COVID-19) is currently unknown via all exposure routes. Animal data are used as surrogates.
• Rhesus macaques are infected with SARS-CoV-2 via the ocular conjunctival and intratracheal route at a dose of 700,000 PFU (106 TCID50).
• A total dose of 700,000 plaque forming units (PFU) of SARS-CoV-2 infected cynomolgus macaques via a combination intranasal and intratracheal exposure (106 TCID50 total dose).109 Macaques did not exhibit clinical symptoms, but shed virus through the nose and throat.
• Please note nonhuman primate infection may not represent human infection.
• Initial experiments suggest that SARSCoV-2 can infect genetically modified mice containing the human ACE2 cell entry receptor. Infection via the intranasal route (dose: 105 TCID50, approximately 70,000 PFU) causes light infection, however no virus was isolated from infected animals, and polymerase chain reaction (PCR) primers used in the study do not align well with SARS-CoV-2, casting doubt on this study.
• The infectious dose for SARS in mice is estimated to be between 67-540 PFU (average 240 PFU, intranasal route).
• Genetically modified mice exposed intranasally to doses of MERS virus between 100 and 500,000 PFU show signs of infection. Infection with higher doses result in severe syndromes.
• High-quality estimates of human transmissibility (R0) range from 2.2 to 3.
• Early estimates of the attack rate in China range from 3%-10%, mainly in households.
• SARS-CoV-2 is believed to spread through close contact and droplet transmission with fomite transmissio, i.e., germs left on surfaces, and close-contact aerosol transmission also plausible.
• SARS-CoV-2 replicates in the upper respiratory tract (e.g., throat), and infectious virus is detectable in throat and lung tissue for at least 8 days
• Pre-symptomatic151 or asymptomatic12 patients can transmit SARS-CoV-2; between 12%54 and 23% 90 of infections may be caused by asymptomatic or pre-symptomatic transmission.
• SARS-CoV-2 is present in infected patient saliva,124 lower respiratory sputum,131 and feces.
• Social distancing and behavioral changes are estimated to have reduced COVID-19 spread by 44% in Hong Kong,47 and a combination of non-pharmaceutical interventions (e.g., school closures, isolation) are likely required to limit transmission.
• Up to 86% of early COVID-19 cases in China were undiagnosed, and these infections were the source for 79% of documented cases.

Host range

• Early genomic analysis indicates similarity to SARS, 154 with a suggested bat origin.
• Analysis of SARS-CoV-2 genomes suggests that a non-bat intermediate species is responsible for the beginning of the outbreak.108 The identity of the intermediate host remains unknown.
• Positive samples from the South China Seafood Market strongly suggests a wildlife source,33 though it is possible that the virus was circulating in humans before the disease was associated with the seafood market.
• Experiments suggest that SARS-CoV2 Spike (S) receptor-binding domain binds the human cell receptor (ACE2) stronger than SARS, 141 potentially explaining its high transmissibility; the same work suggests that differences between SARS-CoV-2 and SARS-CoV Spike proteins may limit the therapeutic ability of SARS antibody treatments.
• Modeling between SARS-CoV-2 Spike and ACE2 proteins suggests that SARS-CoV-2 can bind and infect human, bat, civet, monkey and swine cells.
• There is currently no experimental evidence that SARS-CoV-2 infects domestic animals or livestock, though it is expected that some animal species could be infected

Flattening the curve

Incubation period

• The best current estimate of the COVID-19 incubation period is 5.1 days, with 99% of individuals exhibiting symptoms within 14 days of exposure.
• Fewer than 2.5% of infected individuals show symptoms sooner than 2 days after exposure.
• The reported range of incubation periods is wide, with high-end estimates of 24, 11.3, and 18 days.
• Individuals can test positive for COVID-19 despite lacking clinical symptoms.
• Individuals can be infectious while asymptomatic, and asymptomatic individuals can have similar amounts of virus in their nose and throat as symptomatic individuals.
• Infectious period is unknown, but possibly up to 10-14 days
• On average, there are approximately 4 to 7 days between symptom onset in successive cases of a single transmission chain.

• Most individuals are admitted to the hospital within 8-14 days of symptom onset. • Patients are positive for COVID-19 via PCR for 8-37 days after symptom onset. • Individuals may test positive via PCR for 5-13 days after symptom recovery and hospital discharge.

• The ability of these individuals to infect others is unknown.

• According to the WHO, there is no evidence of re-infection with SARSCoV-2 after recovery. • Experimentally infected macaques were not capable of being reinfected after their primary infection resolved.

Environmental stability

• SARS-CoV-2 can persist on plastic and stainless steel surfaces for up to 3 days (at 21-23oC, 40% RH), with a half-life of 13-16 hours.
• SARS-CoV-2 has an aerosol half-life of 2.7 hours (particles <5 μm, tested at 21-23oC and 65% RH).
• Studies suggest that other coronaviruses can survive on nonporous surfaces up to 9-10 days (MHV, SARS-CoV), and porous surfaces for up to 3-5 days (SARS-CoV) in air conditioned environments (20-25oC, 40-50% RH)
• Coronavirus survival tends to be higher at lower temperatures and lower relative humidity (RH), though infectious virus can persist on surfaces for several days in typical office or hospital conditions
• SARS can persist with trace infectivity for up to 28 days at refrigerated temperatures (4oC) on surfaces.
• Beta-coronaviruses (e.g., SARS-CoV) may be more stable than alphacoronaviruses (HCoV-229E).
• No strong evidence for reduction in transmission with seasonal increase in temperature and humidity.
• One hour after aerosolization approximately 63% of airborne MERS virus remained viable in a simulated office environment (25oC, 75% RH)
• The aerosol survival of related human coronavirus (229E) was relatively high, (half-life of ~67 hours at 20oC and 50% RH), indicating ~20% of infectious virus remained after 6 days.
• Both higher and lower RH reduced HCoV-229E survival; lower temperatures improved survival

Symptoms of COVID-19

Clinical presentation

• The majority of COVID-19 cases are mild (81%, N = 44,000 cases)
• Initial COVID-19 symptoms include fever (87.9% overall, but only 43.8% present with fever initially60), cough (67.7%60), fatigue, shortness of breath, headache, reduction in lymphocyte count.
• Headache37 and diarrhea are uncommon
• Complications include acute respiratory distress (ARDS observed in 17-29% of hospitalized patients, which leads to death in 4-15% of cases, pneumonia, cardiac injury, secondary infection, kidney failure, arrhythmia, sepsis, and shock.
• Approximately 15% of hospitalized patients were classified as severe,60, 120 and approximately 5% of patients were admitted to the ICU.
• Most deaths are caused by respiratory failure or respiratory failure combined with myocardial (heart) damage.
• The case fatality rate (CFR) depends on comorbidities; cardiovascular disease, hypertension, diabetes, and respiratory conditions all increase the CFR.
• The CFR increases with age; individuals older than 60 are at higher risk of death, and >60% of confirmed fatalities have been male.
• Children of all ages are susceptible to COVID-19 though generally present with milder symptoms.
• Severe symptoms in children, however, are possible.
• In the US, 34% of hospitalizations have been individuals less than 44 years old.
• Based on one patient, a productive immune response is generated and sustained for at least 7 days.

Diagnosis

Diagnostic code - ICD-10 code U07.1

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SARS-CoV-2 scanning electron microscope

• PCR protocols and primers have been widely shared among international researchers though PCR-based diagnostic assays do not differentiate between active and inactive virus.
• A combination of pharyngeal (throat) RT-PCR and chest tomography are the most effective diagnostic criteria (correctly diagnosing 91.9% of infections).104 Single throat swabs alone detect 78.2% of true infections, while duplicate tests identify 86.2% of infections.
• Nasal and pharyngeal swabs may be less effective as diagnostic specimens than sputum and bronchoalveolar lavage fluid.
• RT-PCR tests are able to identify asymptomatic cases; SARS-CoV-2 infection was identified in 2/114 individuals previously cleared by clinical assessment.
• The FDA released an Emergency Use Authorization enabling laboratories to develop and use tests in-house for patient diagnosis.
• Updated tests from the US CDC are available to states.
• US CDC has expanded patient testing criteria to include symptomatic patients at clinician discretion.
• Several rapid or real-time test kits have been produced by universities and industry, including the Wuhan Institute of Virology, BGI, and Cepheid
• The US CDC is developing serological tests to determine what proportion of the population has been exposed to SARS-CoV-2.
• Machine learning tools are being developed to predict severe and fatal COVID-19 cases based on CT scans

Treatment

• Treatment for COVID-19 is primarily supportive care, including mechanical ventilation and antibiotics to prevent secondary infection as appropriate.
• Preliminary reports from two clinical trials in China suggest that favipiravir improves lung function and reduces recovery time in COVID-19 patients.
• Early results suggest that tocilizumab may be effective at treating severe COVID-19 cases.
• Press reports of a small clinical trial suggest that chloroquine is effective at reducing symptom duration.
• Combination lopinavir and ritonavir with standard care was no more effective than standard care alone.
• Corticosteroids are commonly given to COVID-19 patients153 at risk of ARDS, but their use is not recommended by the US CDC.
• Multiple entities are working to produce a SARS-CoV-2 vaccine, including NIH/NIAID, Moderna Therapeutics and Gilead Sciences, and Sanofi with HHS.
• Moderna has begun phase 1 clinical vaccine trials in humans in WA state.
• Regeneron Pharmaceuticals has developed potential SARS-CoV-2 antibody therapies.
• The development of a coronavirus fusion inhibitor in the lab suggests efficacy across multiple human coronaviruses.
• Takeda Pharma (Japan) is working to create antibody treatments based on infected patient plasma

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Social distancing

Shortage of ICU beds and ventilators

As many patients with a more severe form of infection with SARS-cov-2, the underlying cause of COVID-19, go in to ARDS leading to respiratory failure, the need for intensive care beds and ventilators in hard hit areas of the world is very high. Lack of these essential facilities can lead to significantly increased mortality and morbidity. The short supply of intensive care beds and ventilators in the United States can be seen from the following numbers - there are fewer than 100,000 ICU beds in the United States, according to a recent analysis by Johns Hopkins Center for Health Security. The center recommended hospitals be able to convert a full 30% of available beds to COVID-19 patients within a week's notice. It recommend expediting discharges, converting single rooms to doubles and converting lobby waiting rooms and classrooms.

Also see APAP for ventilation proposal.

Prevention

There are simple things you can do to help keep yourself and others healthy. Diseases can make anyone sick regardless of their race or ethnicity.

• Fever
• Cough
• Shortness of breath

Seek medical advice if you

• Develop symptoms AND
• Have been in close contact with a person known to have COVID-19 or
• if you live in or have recently been in an area with ongoing spread of COVID-19.

For most people, the immediate risk of becoming seriously ill from the virus that causes COVID-19 is thought to be low. Fear and anxiety about COVID-19 can cause people to avoid or reject others even though they are not at risk for spreading the virus. Older adults and people of any age who have serious underlying medical conditions may be at higher risk for more serious complications from COVID-19.

• Wash your hands often with soap and water for at least 20 seconds, especially after blowing your nose, coughing, or sneezing; going to the bathroom; and before eating or preparing food.
• Avoid touching your eyes, nose, and mouth with unwashed hands.
• Stay home when you are sick.
• Cover your cough or sneeze with a tissue, then throw the tissue in the trash.

See Prevention

Handwashing

Decontamination

• Twice-daily cleaning with sodium dichloroisocyanurate decontaminated surfaces in COVID19 patient hospital rooms.
• Alcohol-based hand rubs are effective at inactivating SARS-CoV-2 in liquid.
• EPA has released a list of SARS-CoV-2 disinfectants, but solutions were not tested on live virus.6 Other Coronaviruses
• Chlorine-based134 and ethanolbased44 solutions recommended.
• Heat treatment at 56oC is sufficient to kill coronaviruses, though effectiveness depends in part on amount of protein in contaminated media
• 70% ethanol, 50% isopropanol, sodium hypochlorite [bleach, 200 ppm], and UV radiation are effective at inactivating several coronaviruses (MHV and CCV)
• Ethanol-based biocides are effective disinfectants against coronaviruses dried on surfaces, including ethanol containing gels similar to hand sanitizer.
• Surface spray disinfectants such as Mikrobac, Dismozon, and Korsolex are effective at reducing infectivity of the closely related SARS-CoV after 30 minutes of contact.
• Coronaviruses may be resistant to thermal inactivation for up to 7 days when stabilized in stool.
• Additionally, coronaviruses are more stable in matrixes such as respiratory sputum.
• Hydrogen peroxide vapor is expected to be effective at repeated decontamination of N95 respirator
• What is the minimal contact time for disinfectants?
• Does contamination with human fluids/waste alter disinfectant efficacy profiles?
• How effective is air filtration at reducing transmission in healthcare, airplanes and public spaces?

Personal protective equipment

• PPE effectiveness for SARS-CoV-2 is currently unknown; SARS is used as a surrogate.
• Healthcare worker illnesses (over 1,000120) demonstrates human-tohuman transmission despite isolation, PPE, and infection control.
• US CDC does not recommend the use of facemasks for healthy people.
• Facemasks should be used by people showing symptoms to reduce the risk of others getting infected.
• The use of facemasks is crucial for health workers and people in close contact with infected patients (at home or in a health care facility).
• “Healthcare personnel entering the room [of SARS-CoV-2 patients] should use standard precautions, contact precautions, airborne precautions, and use eye protection (e.g., goggles or a face shield)”
• WHO indicates healthcare workers should wear clean, non-sterile, longsleeve gowns as well as gloves.
• Respirators (NIOSH-certified N95, EUFFP2 or equivalent) are recommended for those dealing with possible aerosols
• Additional protection, such as a Powered Air Purifying Respirator (PAPR) with a full hood, should be considered for high-risk procedures (i.e., intubation, ventilation)
• SARS-CoV-2 transmission has occurred in hospitals inside130 and outside of China,61 including the US.
• Porous hospital materials, including paper and cotton cloth, maintain infectious SARS-CoV for a shorter time than non-porous material.
• Despite extensive environmental contamination, air sampling in patient rooms did not detect SARS-CoV-2
• Mode of aerosol transmission? Effective distance of spread via droplet or aerosol?
• How effective are barriers such as N95 respirators or surgical masks?
• What is the appropriate PPE for first responders? Airport screeners?
• Proper procedures for reducing spread in medical facilities / transmission rate in medical setting

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Social distancing

Social distancing

Social distancing is a way to keep people from interacting closely or frequently enough to spread an infectious disease. Schools and other gathering places such as movie theaters may close, and sports events and religious services may be cancelled.

What Is Quarantine?

Quarantine separates and restricts the movement of people who have been exposed to a contagious disease to see if they become sick. It lasts long enough to ensure the person has not contracted an infectious disease.

What Is Isolation?

Isolation prevents the spread of an infectious disease by separating people who are sick from those who are not and it lasts as long as the disease remains contagious.

CDC 2019-nCoV Laboratory Test Kit

Case definitions

Here are some of the terms used in surveillance and case definitions. Suspect case A.

• A. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset; OR
• B. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case (see definition of contact) in the last 14 days prior to symptom onset; OR
• C. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation. Global surveillance for COVID-19 caused by human infection with COVID-19 virus.

Probable case A. A suspect case for whom testing for the COVID-19 virus is inconclusive. 1 OR B. A suspect case for whom testing could not be performed for any reason. Confirmed case A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms. See laboratory guidance for details: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technicalguidance/laboratory-guidance

Contact A Contact A is a person who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case: 1. Face-to-face contact with a probable or confirmed case within 1 meter and for more than 15 minutes; 2. Direct physical contact with a probable or confirmed case; 3. Direct care for a patient with probable or confirmed COVID-19 disease without using proper personal protective equipment; OR 4. Other situations as indicated by local risk assessments. Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days before through the 14 days after the date on which the sample was taken which led to confirmation.

A patient with COVID being treated

Prophylaxis

See COVID-19 prophylaxis proposal

Vaccine

A vaccine for COVID-19 is currently not available although several groups are actively working on developing a vaccine.

Latest research

See Latest research on Coronavirus

Economic impact

• COVID-19 is expected to lead to global economic recession with impact lasting months to years.
• See McKinsey report

Frequently Asked Questions

See FAQs

Travel

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Healthcare professionals

• See Latest research on Coronavirus
• Also see CDC healthcare professionals page

Strategies to Optimize PPE & Equipment

• See See CDC guidance

Healthcare Personnel with Potential Exposure to COVID-19

• See COVID-19 prophylaxis proposal

Health agencies

• Coronavirus disease (COVID-19) by the World Health Organization
• Coronavirus 2019 (COVID-19) by the U.S. Centers for Disease Control and Prevention

Directories

• COVID-19 Directory on Curlie
• COVID-19 Resource Directory on OpenMD

Medical journals

• Coronavirus Disease 2019 (COVID-19) by JAMA
• Coronavirus: News and Resources by BMJ Publishing Group
• Novel Coronavirus Information Center by Elsevier
• COVID-19 Resource Centre by The Lancet
• SARS-CoV-2 and COVID-19 by Nature
• Coronavirus (Covid-19) by New England Journal of Medicine
• Covid-19: Novel Coronavirus by Wiley Publishing

COVID vaccine development

WHO preventing coronavirus

Coronavirus: WHO declares COVID 19 a pandemic.

• Prevention
• FAQs on COVID
• Glossary of COVID

Treatments

The monoclonal antibodies treatments Bamlanivimab (made by Eli Lilly and Company) and the therapeutic cocktail Casirivimab/Imdevimab (made by Regeneron) called monoclonal antibodies that can be given to help treat patients with COVID-19.  

List of approved COVID-19 vaccinations in US

The following COVID-19 vaccines have received emergency use authorization from the U.S. Food and Drug Administration for the prevention of COVID-19:

• The Pfizer-BioNTech COVID-19 vaccine for use in persons 16 years of age and older.
• The Moderna COVID-19 vaccine for use in persons 18 years of age and older.
• The Johnson & Johnson (Janssen) COVID-19 vaccine for use in persons 18 years and older.

External links

• US HHS dashboard