Coronavirus Disease 2019

Coronavirus disease 2019
Coronavirus disease 2019 (COVID-19) is an infectious

disease caused by severe acute respiratory syndrome
Coronavirus disease 2019 (COVID-
coronavirus 2 (SARS-CoV-2).[6] The disease was first 19)
identified in December 2019 in Wuhan, the capital of Other names
"Coronavirus"
China's Hubei province, and has since spread globally,
resulting in the ongoing 2019–20 coronavirus 2019-nCoV acute
pandemic.[7][8] Common symptoms include fever, cough, respiratory disease
and shortness of breath.[9] Other symptoms may include Wuhan pneumonia
muscle pain, diarrhea, sore throat, loss of smell, and
Novel coronavirus
abdominal pain.[3][10][11] While the majority of cases
pneumonia[1][2]
result in mild symptoms, some progress to viral
pneumonia and multi-organ failure.[7][12] As of 5 April
2020, more than 1.23 million[5] cases of have been
reported in more than two hundred countries and
territories,[13] resulting in more than 67,200 deaths.[5]
More than 252,000 people have recovered.[5]
The virus is mainly spread during close contact,[a] and by

small droplets produced when people cough, sneeze, or
talk.[4][15][14] These small droplets may be produced
during breathing but the virus is not generally
airborne.[4][15][16] People may also catch COVID-19 by Symptoms of COVID-19
touching a contaminated surface and then their face.[4][14]
Pronunciation /kəˈroʊnəˌvaɪrəs dɪˈziːz,
The virus can survive on surfaces up to 72 hours.[17] It is
most contagious during the first three days after symptom ˈkoʊvɪd/
onset, although spread may be possible before symptoms Specialty Infectious diseases
appear and in later stages of the disease.[18] Time from
Symptoms Fever, cough, shortness of
exposure to onset of symptoms is generally between two
and fourteen days, with an average of five days.[9][19] breath, none[3][4]
The standard method of diagnosis is by reverse Complications Pneumonia, viral sepsis, acute
transcription polymerase chain reaction (rRT-PCR) from respiratory distress syndrome,
a nasopharyngeal swab.[20] The infection can also be kidney failure
diagnosed from a combination of symptoms, risk factors
Usual onset 5 days from exposure (may
and a chest CT scan showing features of
range between 2–14 days)
pneumonia.[21][22]
Causes Severe acute respiratory
Recommended measures to prevent infection include syndrome coronavirus 2
frequent hand washing, social distancing (maintaining (SARS-CoV-2)
physical distance from others, especially from those with
symptoms), covering coughs and sneezes with a tissue or Risk factors Travel, viral exposure
inner elbow, and keeping unwashed hands away from the Diagnostic rRT-PCR testing, CT scan
face.[23][24] The use of masks is recommended for those method
who suspect they have the virus and their caregivers.[25]
Prevention Hand washing, quarantine,
Recommendations for mask use by the general public
social distancing
vary, with some authorities recommending against their
use, some recommending their use, and others requiring Treatment Symptomatic and supportive
their use.[26][27][28] Currently, there is no vaccine or Frequency 1,237,420[5] confirmed cases
specific antiviral treatment for COVID-19.[4]
Management involves treatment of symptoms, supportive Deaths 67,260 (5.4% of confirmed
care, isolation, and experimental measures.[29] cases)[5]
The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a Public Health
Emergency of International Concern (PHEIC)[30][31] on 30 January 2020, and a pandemic on 11 March
2020.[8] Local transmission of the disease has been recorded in many countries across all six WHO
regions.[32]
Contents
Signs and symptoms
Cause
Transmission
Virology
Pathophysiology
Diagnosis Play media
Pathology Video summary (script)
Prevention
Management
Medications
Personal protective equipment
Mechanical ventilation
Acute respiratory distress syndrome
Experimental treatment
Information technology
Psychological support
Prognosis
Reinfection
History
Epidemiology
Society and culture
Terminology
Manufacturing
Misinformation
Research
Vaccine
Post-infection treatments
Anti-cytokine storm
Passive antibody therapy
See also
Notes
References
External links
Signs and symptoms

Those infected with the virus may be asymptomatic or develop
Symptom[33] %
flu-like symptoms, including fever, cough, fatigue, and
shortness of breath.[3][37][38] Emergency symptoms include Fever 88
difficulty breathing, persistent chest pain or pressure, Dry cough 68
confusion, difficulty waking, and bluish face or lips; immediate
Fatigue 38
medical attention is advised if these symptoms are present.[39]
Less commonly, upper respiratory symptoms, such as sneezing, Sputum production 33
runny nose, or sore throat may be seen. Symptoms such as Loss of smell 15[34] to 30[11][35]
nausea, vomiting, and diarrhea have been observed in varying
Shortness of breath 19
percentages.[36][40][41] Some cases in China initially presented
only with chest tightness and palpitations.[42] In March 2020 Muscle or joint pain 15
there were reports indicating that loss of the sense of smell Sore throat 14
(anosmia) may be a common symptom among those who have
Headache 14
mild disease,[11][35] although not as common as initially
reported.[34] In some, the disease may progress to pneumonia, Chills 11
multi-organ failure, and death.[7][12] In those who develop Nausea or vomiting 5
severe symptoms, time from symptom onset to needing
Nasal congestion 5
mechanical ventilation is typically eight days.[43]
Diarrhoea 4 to 31[36]
As is common with infections, there is a delay between the
Haemoptysis 0.9
moment when a person is infected with the virus and the time
when they develop symptoms. This is called the incubation Conjunctival congestion 0.8
period. The incubation period for COVID-19 is typically five
to six days but may range from two to 14 days.[44][45] 97.5% of people who develop symptoms will do so
within 11.5 days of infection.[46]
Reports indicate that not all who are infected develop symptoms, but their role in transmission is
unknown.[47] Preliminary evidence suggests asymptomatic cases may contribute to the spread of the
disease.[48][49] The proportion of infected people who do not display symptoms is currently unknown and
being studied, with South Korea's CDC reporting that 20% of all confirmed cases remained asymptomatic
during their hospital stay.[49][50]
Cause
Transmission
Some details about how the disease is spread are still being determined.[14][15] The WHO and CDC say it is
primarily spread during close contact and by small droplets produced when people cough, sneeze, or
talk;[4][14] with close contact being within 1–3 m (3 ft 3 in–9 ft 10 in).[4] A study in Singapore found that an
uncovered coughing can lead to droplets travelling up to 4.5 meters (15 feet).[51][52]
Respiratory droplets may also be produced during breathing out,
including when talking. Though the virus is not generally
airborne,[4][53] The National Academy of Science has suggested that
bioaerosol transmission may be possible and air collectors
positioned in the hallway outside of people's rooms yielded samples
positive for viral RNA.[54] The droplets can land in the mouths or
noses of people who are nearby or possibly be inhaled into the
lungs.[55] Some medical procedures such as intubation and
cardiopulmonary resuscitation (CPR) may cause respiratory Respiratory droplets, produced when
secretions to be aerosolised and thus result in airborne spread.[53] It a man is sneezing
may also spread when one touches a contaminated surface, known as
fomite transmission, and then touches their eyes, nose, or mouth.[4]
While there are concerns it may spread by feces, this risk is believed
to be low.[4][14]
The virus is most contagious when people are symptomatic; while

spread may be possible before symptoms appear, this risk is
low.[4][14] The European Centre for Disease Prevention and Control
(ECDC) says while it is not entirely clear how easily the disease
spreads, one person generally infects two to three others.[15] Play media
A video discussing the basic
The virus survives for hours to days on surfaces.[4][15] Specifically, reproduction number and case
the virus was found to be detectable for one day on cardboard, for up fatality rate in the context of the
to three days on plastic and stainless steel, and for up to four hours pandemic
on copper.[17] This, however, varies based on the humidity and
temperature.[56][57] Surfaces may be decontaminated with a number
of solutions (within one minute of exposure to the disinfectant for a stainless steel surface), including 62–
71% ethanol, 50–100% isopropanol, 0.1% sodium hypochlorite, 0.5% hydrogen peroxide, and 0.2–7.5%
povidone-iodine. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less
effective.[58]
Virology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a

novel severe acute respiratory syndrome coronavirus, first isolated
from three people with pneumonia connected to the cluster of acute
respiratory illness cases in Wuhan.[59] All features of the novel
SARS-CoV-2 virus occur in related coronaviruses in nature.[60]
Outside the human body, the virus is killed by household soap,
which bursts its protective bubble.[61]
SARS-CoV-2 is closely related to the original SARS-CoV.[62] It is

thought to have a zoonotic origin. Genetic analysis has revealed that Illustration of SARSr-CoV virion
the coronavirus genetically clusters with the genus Betacoronavirus,
in subgenus Sarbecovirus (lineage B) together with two bat-derived
strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov
RaTG13).[33] In February 2020, Chinese researchers found that there is only one amino acid difference in
certain parts of the genome sequences between the viruses from pangolins and those from humans, however,
whole-genome comparison to date found at most 92% of genetic material shared between pangolin
coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.[63]
Pathophysiology
The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme
ACE2, which is most abundant in the type II alveolar cells of the lungs. The virus uses a special surface
glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell.[64] The density of
ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested that
decreasing ACE2 activity might be protective,[65][66] though another view is that increasing ACE2 using
angiotensin II receptor blocker medications could be protective and that these hypotheses need to be
tested.[67] As the alveolar disease progresses, respiratory failure might develop and death may follow.[66]
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of
gastric, duodenal and rectal epithelium[68] as well as endothelial cells and enterocytes of the small
intestine.[69]
The expanding part of the lungs, pulmonary alveoli, contain two main types of functioning cells. One cell,
type I, absorbs from the air, i.e. gas exchange. The other, type II, produces surfactants, which serve to keep
the lungs fluid, clean, infection free, etc. COVID-19 finds a way into a surfactant producing type II cell, and
smothers it by reproducing COVID-19 virus within it. Each type II cell which perishes to the virus causes an
extreme reaction in the lungs. Fluids, pus, and dead cell material flood the lung, causing the coronavirus
pulmonary disease.[70]
Diagnosis
The WHO has published several testing protocols for the disease.[72]
The standard method of testing is real-time reverse transcription
polymerase chain reaction (rRT-PCR).[73] The test is typically done
on respiratory samples obtained by a nasopharyngeal swab, however
a nasal swab or sputum sample may also be used.[20][74] Results are
generally available within a few hours to two days.[75][76] Blood
tests can be used, but these require two blood samples taken two
Demonstration of a nasopharyngeal
weeks apart and the results have little immediate value.[77] Chinese swab for COVID-19 testing
scientists were able to isolate a strain of the coronavirus and publish
the genetic sequence so laboratories across the world could
independently develop polymerase chain reaction (PCR) tests to
detect infection by the virus.[7][78][79] As of 19 March 2020,
antibody tests (which may detect active infections and whether a
person had been infected in the past) were in development, but not
yet widely used.[80][81] The FDA approved the first point-of-care
test on 21 March 2020 for use at the end of that month.[82]
Diagnostic guidelines released by Zhongnan Hospital of Wuhan

University suggested methods for detecting infections based upon
clinical features and epidemiological risk. These involved
identifying people who had at least two of the following symptoms CDC rRT-PCR test kit for COVID-
in addition to a history of travel to Wuhan or contact with other 19[71]
infected people: fever, imaging features of pneumonia, normal or
reduced white blood cell count, or reduced lymphocyte count.[21]
A March 2020 review concluded that chest X-rays are of little value in early stages, whereas CT scans of the
chest are useful even before symptoms occur.[61] Typical features on CT include bilateral multilobar ground-
glass opacificities with a peripheral, asymmetric and posterior distribution.[61] Subpleural dominance, crazy
paving (lobular septal thickening with variable alveolar filling) and consolidation develop as the disease
evolves.[83] As of March 2020, the American College of Radiology recommends that "CT should not be
used to screen for or as a first-line test to diagnose COVID-19".[84]
Typical CT imaging findings CT imaging of rapid progression stage
Pathology
Few data are available about microscopic lesions and the pathophysiology of COVID-19.[85][86] The main
pathological findings at autopsy are:
Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema

Four types of severity of viral pneumonia can be observed:
minor pneumonia: minor serous exudation, minor fibrin exudation
mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical
pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant
cell formation
severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. This
diffuse DAD is responsible of the acute respiratory distress syndrome (ARDS) and severe
hypoxemia observed in this disease.
healing pneumonia: organization of exudates in alveolar cavities, and pulmonary interstitial
fibrosis
plasmocytosis in BAL[87]
Blood: disseminated intravascular coagulation (DIC);[88] leukoerythroblastic reaction[89]
Liver: microvesicular steatosis
Prevention
Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places,
washing hands with soap and water often and for at least 20 seconds, practicing good respiratory hygiene
and avoiding touching the eyes, nose, or mouth with unwashed hands.[95][96][97] The CDC recommends
covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of
the elbow if no tissue is available.[95] They also recommend proper hand hygiene after any cough or
sneeze.[95] Social distancing strategies aim to reduce contact of infected persons with large groups by
closing schools and workplaces, restricting travel, and cancelling mass gatherings.[98] Social distancing also
includes that people stay at least six feet apart (1.83 meters).[99]
As a vaccine is not expected until 2021 at the earliest,[100] a key part of managing COVID-19 is trying to
decrease the epidemic peak, known as "flattening the curve".[91] This is done by slowing the infection rate
to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and
delaying additional cases until effective treatments or a vaccine become available.[91]
According to the WHO, the use of masks is
recommended only if a person is coughing or
sneezing or when one is taking care of someone
with a suspected infection.[101] Some countries also
recommend healthy individuals to wear face masks,
including China,[102] Hong Kong,[103]
Thailand,[104] Czech Republic,[105] and
Austria.[106] In order to meet the need for masks,
the WHO estimates that global production will
need to increase by 40%. Hoarding and speculation
have worsened the problem, with the price of
Inhibiting new infections to reduce the number of cases
masks increasing sixfold, N95 respirators tripled,
at any given time—known as flattening the curve—
and gowns doubled.[107] Some health experts allows healthcare services to better manage the same
consider wearing non-medical grade masks and volume of patients.[90][91][92]
other face coverings like scarves or bandanas a
good way to prevent people from touching their
mouths and noses, even if non-medical coverings
would not protect against a direct sneeze or cough
from an infected person.[108]
Those diagnosed with COVID-19 or who believe

they may be infected are advised by the CDC to
stay home except to get medical care, call ahead
before visiting a healthcare provider, wear a face
mask before entering the healthcare provider's
office and when in any room or vehicle with
another person, cover coughs and sneezes with a
tissue, regularly wash hands with soap and water, Alternatives to flattening the curve[93][94]
and avoid sharing personal household
items.[109][110] The CDC also recommends that
individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet
or when hands are visibly dirty, before eating and after blowing one's nose, coughing, or sneezing. It further
recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water
are not readily available.[95]
For areas where commercial hand sanitisers are not readily available, WHO provides two formulations for
local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol.
Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for
hand antisepsis". Glycerol is added as a humectant.[111]
Prevention efforts are multiplicative, with
effects far beyond that of a single spread.
Each avoided case leads to more avoided
cases down the line, which in turn can stop
the outbreak in its tracks.
Play media
Handwashing instructions
Management
People are managed with supportive care, which may include fluid, oxygen support, and supporting other
affected vital organs.[113][114][115] The CDC recommends that those who suspect they carry the virus wear a
simple face mask.[25] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of
respiratory failure, but its benefits are still under consideration.[116][117]
The WHO and Chinese National Health Commission have published recommendations for taking care of
people who are hospitalised with COVID-19.[118][119] Intensivists and pulmonologists in the U.S. have
compiled treatment recommendations from various agencies into a free resource, the IBCC.[120][121]
Medications
Some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line
use.[122][123] The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as
ibuprofen for symptoms,[124] and the FDA says currently there is no evidence that NSAIDs worsen COVID-
19 symptoms.[125]
While theoretical concerns have been raised about ACE inhibitors
and angiotensin receptor blockers, as of 19 March 2020, these are
not sufficient to justify stopping these medications.[126][127][128]
Steroids such as methylprednisolone are not recommended unless
the disease is complicated by acute respiratory distress
syndrome.[129][130]
Personal protective equipment
Precautions must be taken to minimise the risk of virus transmission,

especially in healthcare settings when performing procedures that
can generate aerosols, such as intubation or hand ventilation.[131]
For healthcare professionals caring for people with COVID19, the
CDC recommends placing the person in an Airborne Infection
Isolation Room (AIIR) in addition to using standard precautions,
contact precautions, and airborne precautions.[132]
CDC outlines the specific guidelines for the use of personal

protective equipment (PPE) during the pandemic. The recommended
gear includes:
respirator or facemask[133][134]
gown[135]
Four steps to putting on personal
medical gloves[136][137]
protective equipment[112]
eye protection[138]
When available, respirators (instead of facemasks) are preferred.[139] N95 respirators are approved for
industrial settings but the FDA has authorised the masks for use under an Emergency Use Authorization
(EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific
biological agent is not guaranteed for off-label uses.[140] When masks are not available the CDC
recommends using face shields, or as a last resort homemade masks.[141]
Mechanical ventilation
Most cases of COVID-19 are not severe enough to require mechanical ventilation (artificial assistance to
support breathing), but a percentage of cases do.[142][143] Some Canadian doctors recommend the use of
invasive mechanical ventilation because this technique limits the spread of aerosolised transmission
vectors.[142] Severe cases are most common in older adults (those older than 60 years[142] and especially
those older than 80 years).[144] Many developed countries do not have enough hospital beds per capita,
which limits a health system's capacity to handle a sudden spike in the number of COVID-19 cases severe
enough to require hospitalization.[145] This limited capacity is a significant driver of the need to flatten the
curve (to keep the speed at which new cases occur and thus the number of people sick at one point in time
lower).[145] One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical
support of ventilation, and 1.4% died.[116] Around 20–30% of the people in hospital with pneumonia from
COVID19 needed ICU care for respiratory support.[146]
Acute respiratory distress syndrome

Mechanical ventilation becomes more complex as ARDS develops in COVID-19 and oxygenation becomes
increasingly difficult.[147] Ventilators capable of pressure control modes and high PEEP[148] are needed to
maximise oxygen delivery while minimizing the risk of ventilator-associated lung injury and
pneumothorax.[149] High PEEP may not be available on older ventilators.
Options for ARDS[147]

Therapy Recommendations
High-flow nasal oxygen For SpO2 <93%. May prevent the need for intubation and ventilation
Tidal volume 6mL per kg and can be reduced to 4mL/kg
Keep below 30 cmH2O if possible (high respiratory rate (35 per minute) may be
Plateau airway pressure
required)
Positive end-expiratory
Moderate to high levels
pressure
Prone positioning For worsening oxygenation
Fluid management Goal is a negative balance of 1/2–1L per day
Antibiotics For secondary bacterial infections
Glucocorticoids Not recommended
Experimental treatment
No medications are approved to treat the disease by the WHO although some are recommended by
individual national medical authorities.[150] Research into potential treatments started in January 2020,[151]
and several antiviral drugs are in clinical trials.[152][153] Although new medications may take until 2021 to
develop,[154] several of the medications being tested are already approved for other uses, or are already in
advanced testing.[150] Antiviral medication may be tried in people with severe disease.[113] The WHO
recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[155]
Information technology
In February 2020, China launched a mobile app to deal with the disease outbreak.[156] Users are asked to
enter their name and ID number. The app is able to detect 'close contact' using surveillance data and
therefore a potential risk of infection. Every user can also check the status of three other users. If a potential
risk is detected, the app not only recommends self-quarantine, it also alerts local health officials.[157]
Big data analytics on cellphone data, facial recognition technology, mobile phone tracking and artificial
intelligence are used to track infected people and people whom they contacted in South Korea, Taiwan, and
Singapore.[158][159] In March 2020, the Israeli government enabled security agencies to track mobile phone
data of people supposed to have coronavirus. The measure was taken to enforce quarantine and protect those
who may come into contact with infected citizens.[160] Also in March 2020, Deutsche Telekom shared
aggregated phone location data with the German federal government agency, Robert Koch Institute, in order
to research and prevent the spread of the virus.[161] Russia deployed facial recognition technology to detect
quarantine breakers.[162] Italian regional health commissioner Giulio Gallera said he has been informed by
mobile phone operators that "40% of people are continuing to move around anyway".[163] German
government conducted a 48 hours weekend hackathon with more than 42.000 participants.[164][165] Also the
president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of
coronavirus.[166]
Psychological support
Individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of
the infection itself. To address these concerns, the National Health Commission of China published a
national guideline for psychological crisis intervention on 27 January 2020.[167][168]
Prognosis
The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms,
resembling other common upper respiratory diseases such as the common cold. Mild cases typically recover
within two weeks, while those with severe or critical diseases may take three to six weeks to recover.
Among those who have died, the time from symptom onset to death has ranged from two to eight weeks.[33]
Children are susceptible to the disease, but are likely to have milder symptoms and a lower chance of severe
disease than adults; in those younger than 50 years, the risk of death is less than 0.5%, while in those older
than 70 it is more than 8%.[171][172] Pregnant women may be at higher risk for severe infection with
COVID-19 based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is
lacking.[173][174]
In some people, COVID-19 may affect the lungs causing pneumonia. In those most severely affected,
COVID-19 may rapidly progress to acute respiratory distress syndrome (ARDS) causing respiratory failure,
septic shock, or multi-organ failure.[175][176] Complications associated with COVID-19 include sepsis,
abnormal clotting, and damage to the heart, kidneys, and liver. Clotting abnormalities, specifically an
increase in prothrombin time, have been described in 6% of those admitted to hospital with COVID-19,
while abnormal kidney function is seen in 4% of this group.[177] Liver injury as shown by blood markers of
liver damage is frequently seen in severe cases.[178]
Some studies have found that the neutrophil to lymphocyte ratio (NLR) may be helpful in early screening
for severe illness.[179]
Many of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension,
diabetes mellitus, and cardiovascular disease.[180] The Istituto Superiore di Sanità reported that out of 8.8%
of deaths where medical charts were available for review, 97.2% of sampled patients had at least one
comorbidity with the average patient having 2.7 diseases.[181] According to the same report, the median
time between onset of symptoms and death was ten days, with five being spent hospitalised. However,
patients transferred to an ICU had a median time of seven days between hospitalization and death.[181] In a
study of early cases, the median time from exhibiting initial symptoms to death was 14 days, with a full
range of six to 41 days.[182] In a study by the National Health Commission (NHC) of China, men had a
death rate of 2.8% while women had a death rate of 1.7%.[183] Histopathological examinations of post-
mortem lung samples show diffuse alveolar damage with cellular fibromyxoid exudates in both lungs. Viral
cytopathic changes were observed in the pneumocytes. The lung picture resembled acute respiratory distress
syndrome (ARDS).[33] In 11.8% of the deaths reported by the National Health Commission of China, heart
damage was noted by elevated levels of troponin or cardiac arrest.[42]
Availability of medical resources and the socioeconomics of a region may also affect mortality.[184]
Estimates of the mortality from the condition vary because of those regional differences,[185] but also
because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be
overestimated.[186] However, the fact that deaths are the result of cases contracted in the past can mean the
current mortality rate is underestimated.[187][188]
Concerns have been raised about long-
term sequelae of the disease. The Hong
Kong Hospital Authority found a drop of
20% to 30% in lung capacity in some
people who recovered from the disease,
and lung scans suggested organ
damage.[189]
The severity of diagnosed COVID-19 cases in China[169]
Case fatality rates by age group in China. Data through 11

February 2020.[170]
Case fatality rate in China depending on other health problems.

Data through 11 February 2020.[170]
The number of deaths vs total cases by country and approximate
case fatality rate
Case fatality rates (%) by age and country

Age 0–9 10–19 20–29 30–39 40–49 50–59 60–69 70–79 80-89 90+
China as of 11 February[170] 0.0 0.2 0.2 0.2 0.4 1.3 3.6 8.0 14.8
Denmark as of 3 April[190] 0.0 0.0 0.0 0.0 0.0 0.0 3.1 8.7 18.1 34.8
Italy as of 2 April[191] 0.0 0.0 0.1 0.4 0.8 2.3 8.0 21.8 30.9 28.7
Netherlands as of 3 April[192] 0.0 0.0 0.0 0.1 0.1 1.0 5.4 14.9 25.1 21.3
South Korea as of 3
0.0 0.0 0.0 0.1 0.2 0.6 1.9 7.3 18.9
April[193]
Spain as of 2 April[194] 0.0 0.2 0.2 0.3 0.4 1.0 3.2 10.6 21.5 25.9
Case fatality rates (%) by age in the United States

Age 0–19 20–44 45–54 55–64 65–74 75–84 85+
United States as of 16 March[195] 0.0 0.1–0.2 0.5–0.8 1.4–2.6 2.7–4.9 4.3–10.5 10.4–27.3
Note: The lower bound includes all cases. The upper bound excludes cases that were missing data.
Reinfection
As of March 2020, it was unknown if past infection provides effective and long-term immunity in people
who recover from the disease.[196] Immunity is seen as likely, based on the behaviour of other
coronaviruses,[197] but cases in which recovery from COVID-19 have been followed by positive tests for
coronavirus at a later date have been reported.[198][199] It is unclear if these cases are the result of
reinfection, relapse, or testing error.
History
The virus is thought to be natural and have an animal origin,[60] through spillover infection.[200] The origin
is unknown but by December 2019 the spread of infection was almost entirely driven by human-to-human
transmission.[170][201] The earliest reported infection has been unofficially reported to have occurred on 17
November 2019 in Wuhan, China.[202] A study of the first 41 cases of confirmed COVID-19, published in
January 2020 in The Lancet, revealed the earliest date of onset of symptoms as 1 December
2019.[203][204][205] Official publications from the WHO reported the earliest onset of symptoms as
8 December 2019.[202]
Epidemiology
Several measures are commonly used to quantify mortality.[206] These numbers vary by region and over
time, and are influenced by the volume of testing, healthcare system quality, treatment options, time since
initial outbreak, and population characteristics such as age, sex, and overall health.[207] In late 2019, WHO
assigned the emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection
and U07.2 for deaths from clinically or epidemiologically diagnosed COVID-19 without lab-confirmed
SARS-CoV-2 infection.[208]
The death-to-case ratio reflects the number of deaths divided by the number of diagnosed cases within a
given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 5.4%
(67,260/1,237,420) as of 5 April 2020.[5] The number varies by region.[209]
Other measures include the case fatality rate (CFR), which reflects the percent of diagnosed individuals who
die from a disease, and the infection fatality rate (IFR), which reflects the percent of infected individuals
(diagnosed and undiagnosed) who die from a disease. These statistics are not time bound and follow a
specific population from infection through case resolution. A number of academics have attempted to
calculate these numbers for specific populations.[210] In the epicenter of the outbreak in Italy, Castiglione
d'Adda, a small vilage of 4500, 80 (1.8%) are already dead. Most people in the village appear to have
developed antibodies and plausible immunity, most did so without being diagnosed, and many did not have
symptoms.[211][212] An investigation is underway to test the entire population to learn more about the
disease.[213]
Total confirmed cases over time Total deaths over time
Total confirmed cases of COVID-19 per Total confirmed deaths due to COVID-19
million people, 20 March 2020[214] per million people, 24 March 2020[215]
Society and culture
Terminology
The World Health Organization announced in February 2020 that COVID-19 is the official name of the
disease. World Health Organization chief Tedros Adhanom Ghebreyesus explained that CO stands for
corona, VI for virus and D for disease, while 19 is for when the outbreak was first identified: 31 December
2019.[216] The name had been chosen to avoid references to a specific geographical location (e.g. China),
animal species, or group of people, in line with international recommendations for naming aimed at
preventing stigmatisation.[217][218]
The virus that causes COVID-19 is named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2).[219] The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in
public communications.[219] Coronaviruses were named in 1968 for their appearance in electron
micrographs which was reminiscent of the solar corona, corona meaning crown in Latin.[220][221][222] Both
the disease and virus are commonly referred to as "coronavirus".
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as
"coronavirus" and "Wuhan coronavirus".[223][224][225] In January 2020, WHO recommended 2019-
nCov[226] and 2019-nCoV acute respiratory disease[227] as interim names for the virus and disease in
accordance with 2015 guidance against using locations in disease and virus names.[228] The official names
COVID-19 and SARS-CoV-2 were issued on 11 February 2020.[229][230]
Following the official naming of the virus and disease, controversial terms, such as "Wuflu" and "Kung
Flu", emerged as offensive ways of describing COVID-19. Use of these terms (popularised in social media
and alt-right sources) not only downplays the seriousness of the deadly disease but also misinforms by
suggesting it is a strain of influenza (when it is not a flu), while simultaneously mocking Chinese
culture.[231][232]
Manufacturing
Due to failures in the supply chains, digital manufacturers are working to make healthcare material such as
nasal swabs and ventilator parts.[233][234] An Italian startup employed 3D printing technology to produce
valves for ventilators.[235] 3D printed valves costed $1 instead of $10,000 and were ready overnight.[236]
Misinformation
After the initial outbreak of COVID-19, conspiracy theories, misinformation, and disinformation emerged
regarding the origin, scale, prevention, treatment, and other aspects of the disease and rapidly spread
online.[237][238][239][240]
Research
International clinical research programs on vaccines and therapeutic drug candidates having potential to
reduce illnesses caused by COVID-19 are underway by government organizations, academic groups, and
industry researchers.[241][242] In March, the World Health Organization initiated the "SOLIDARITY Trial"
in 10 countries, enrolling thousands of people infected with COVID-19 to assess treatment effects of four
existing antiviral compounds with the most promise of efficacy.[243]
Personal hygiene and a healthy lifestyle and diet have been recommended to improve immunity.[244]
Vaccine
There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous
work on SARS-CoV is being utilised because SARS-CoV-2 and SARS-CoV both use the ACE2 receptor to
enter human cells.[245] There are three vaccination strategies being investigated. First, researchers aim to
build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune
response of the human body to a new infection with COVID-19. A second strategy, subunit vaccines, aims
to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-
CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor.
A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a
vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and
efficacy.[246]
On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle. The vaccine
contains a harmless genetic code copied from the virus that causes the disease.[247]
Post-infection treatments
According to two organizations tracking clinical trial progress on potential therapeutic drugs for COVID-19
infections, 29 Phase II-IV efficacy trials were concluded in March 2020 or scheduled to provide results in
April from hospitals in China – which experienced the first outbreak of COVID-19 in late 2019.[248][249]
Seven trials were evaluating repurposed drugs already approved to treat malaria, including four studies on
hydroxychloroquine or chloroquine phosphate.[249] Repurposed antiviral drugs make up most of the Chinese
research, with nine Phase III trials on remdesivir across several countries due to report by the end of
April.[248][249] Other potential therapeutic candidates under pivotal clinical trials concluding in March–April
are vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-
converting enzyme 2, among others.[249]
The COVID-19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals
by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic
compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data, and 4) facilitate
sharing of clinical trial outcomes before publication.[250][251] A dynamic review of clinical development for
COVID-19 vaccine and drug candidates was in place, as of April 2020.[251]
Several existing antiviral medications are being evaluated for treatment of COVID-19,[150] including
remdesivir, chloroquine and hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir combined with
interferon beta.[243][252] There is tentative evidence for efficacy by remdesivir, as of March 2020.[253]
Remdesivir inhibits SARS-CoV-2 in vitro.[254] Phase 3 clinical trials are being conducted in the U.S., China,
and Italy.[150][248][255]
Chloroquine, previously used to treat malaria, was studied in China in February 2020, with positive
preliminary results.[256] However, there are calls for peer review of the research.[257] The Guangdong
Provincial Department of Science and Technology and the Guangdong Provincial Health and Health
Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and
shortens the length of person's hospital stay" and recommended it for people diagnosed with mild, moderate
and severe cases of novel coronavirus pneumonia.[258]
On 17 March, the Italian Pharmaceutical Agency included chloroquine and hydroxychloroquine in the list of
drugs with positive preliminary results for treatment of COVID-19.[259] Korean and Chinese Health
Authorities recommend the use of chloroquine.[260][261] However, the Wuhan Institute of Virology, while
recommending a daily dose of one gram, notes that twice that dose is highly dangerous and could be lethal.
On 28 March 2020, the FDA issued an emergency use authorization for hydroxychloroquine and
chloroquine at the discretion of physicians treating people with COVID-19.[262][263]
The Chinese 7th edition guidelines also include interferon, ribavirin, or umifenovir for use against COVID-
19.[261]
In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness.[264]
Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration
inhibition of SARS-CoV-2.[254]
Studies have demonstrated that initial spike protein priming by transmembrane protease serine 2
(TMPRSS2) is essential for entry of SARS-CoV-2 via interaction with the ACE2 receptor.[265] These
findings suggest that the TMPRSS2 inhibitor camostat approved for use in Japan for inhibiting fibrosis in
liver and kidney disease might constitute an effective off-label treatment.
In February 2020, favipiravir was being studied in China for experimental treatment of the emergent
COVID-19 disease.[266][267]
In April 2020 Ivermectin is being studied in Australia for a possible treatment for COVID-19 and has been
shown to stop viral growth within 48 hours in vitro.[268][269]
There are mixed results as of April 3 as to the effectiveness of Hydroxychloroquine as a treatment for
COVID-19. With studies showing either little to no improvement over the control groups.[270]
Anti-cytokine storm
Cytokine storm can be a complication in the later stages of severe COVID-19. There is evidence that
hydroxychloroquine may have anti-cytokine storm properties.[271]
Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small
study was completed.[272][273] It is undergoing a phase 2 non randomised test at the national level in Italy
after showing positive results in people with severe disease.[259][274][275] Combined with a serum ferritin
blood test to identify cytokine storms, it is meant to counter such developments, which are thought to be the
cause of death in some affected people.[276][277][278] The interleukin-6 receptor antagonist was approved by
the FDA for treatment against cytokine release syndrome induced by a different cause, CAR T cell therapy,
in 2017.[279]
The Feinstein Institute of Northwell Health announced in March a study on "a human antibody that may
prevent the activity" of IL-6.[280]
Passive antibody therapy
Transferring purified and concentrated antibodies produced by the immune systems of those who have
recovered from COVID-19 to people who need them is being investigated as a non-vaccine method of
passive immunisation.[281] This strategy was tried for SARS with inconclusive results.[281] Viral
neutralization is the anticipated mechanism of action by which passive antibody therapy can mediate
defence against SARS-CoV-2. Other mechanisms however, such as antibody-dependent cellular cytotoxicity
and/or phagocytosis, may be possible.[281] Other forms of passive antibody therapy, for example, using
manufactured monoclonal antibodies, are in development.[281] Production of convalescent serum, which
consists of the liquid portion of the blood from recovered patients and contains antibodies specific to this
virus, could be increased for quicker deployment.[282]
See also
Coronavirus diseases, a group of closely related syndromes
Li Wenliang, a doctor at Central Hospital of Wuhan, who later contracted and died of COVID-
19 after raising awareness of the spread of the virus.
Disease X, a World Health Organisation term
Notes
a. Close contact is defined as one metre (three feet) by WHO[4] and two metres (six feet) by the
CDC[14]
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External links
Health agencies:
Coronavirus disease (COVID-19) (https://www.who.int/emergencies/diseases/novel-coronaviru

s-2019) by the World Health Organization
Coronavirus 2019 (COVID-19) (https://www.cdc.gov/coronavirus/2019-ncov/index.html) by the
U.S. Centers for Disease Control and Prevention
Directories:
COVID-19 (https://curlie.org/Health/Conditions_and_Diseases/Respiratory_Disorders/COVID-1
9) at Curlie
COVID-19 Resource Directory on OpenMD (https://openmd.com/directory/covid-19)
Medical journals:
Coronavirus Disease 2019 (COVID-19) (https://jamanetwork.com/journals/jama/pages/coronav

irus-alert) by JAMA
Coronavirus: News and Resources (https://www.bmj.com/coronavirus) by the BMJ Publishing
Group
Novel Coronavirus Information Center (https://www.elsevier.com/connect/coronavirus-informati
on-center) by Elsevier
COVID-19 Resource Centre (https://www.thelancet.com/coronavirus) by The Lancet
SARS-CoV-2 and COVID-19 (https://www.springernature.com/gp/researchers/campaigns/coro
navirus) by Nature
Coronavirus (Covid-19) (https://www.nejm.org/coronavirus) by the New England Journal of
Medicine
Covid-19: Novel Coronavirus (https://novel-coronavirus.onlinelibrary.wiley.com/) by Wiley
Publishing
Other:
Epidemiology simulator (http://gabgoh.github.io/COVID/index.html)

Classification ICD-10: U07.1 (htt D
ps://icd.who.int/bro
wse10/2019/en#/U0
7.1), U07.2 (https://i
cd.who.int/browse1
0/2019/en#/U07.2) ·
MeSH:
C000657245 (http
s://www.nlm.nih.go
v/cgi/mesh/2015/M
B_cgi?field=uid&ter
m=C000657245) ·
SNOMED CT:
840539006 (http://s
nomed.info/id/8405
39006)
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Coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is an infectious

The virus is mainly spread during close contact,[a] and by

Signs and symptoms

The virus is most contagious when people are symptomatic; while

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a

SARS-CoV-2 is closely related to the original SARS-CoV.[62] It is

Diagnostic guidelines released by Zhongnan Hospital of Wuhan

Typical CT imaging findings CT imaging of rapid progression stage

Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema

Those diagnosed with COVID-19 or who believe

Personal protective equipment

Precautions must be taken to minimise the risk of virus transmission,

CDC outlines the specific guidelines for the use of personal

Acute respiratory distress syndrome

Options for ARDS[147]

The severity of diagnosed COVID-19 cases in China[169]

Case fatality rates by age group in China. Data through 11

Case fatality rate in China depending on other health problems.

Case fatality rates (%) by age and country

Case fatality rates (%) by age in the United States

Society and culture

Passive antibody therapy

Coronavirus disease (COVID-19) (https://www.who.int/emergencies/diseases/novel-coronaviru

Coronavirus Disease 2019 (COVID-19) (https://jamanetwork.com/journals/jama/pages/coronav

Epidemiology simulator (http://gabgoh.github.io/COVID/index.html)

Retrieved from "https://en.wikipedia.org/w/index.php?title=Coronavirus_disease_2019&oldid=949287825"

This page was last edited on 5 April 2020, at 16:52 (UTC).

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