Coronavirus disease 2019
|Coronavirus disease 2019 (COVID-19)|
|Symptoms of COVID-19|
|Symptoms||Fever, cough, shortness of breath, none|
|Complications||Pneumonia, viral sepsis, acute respiratory distress syndrome, kidney failure|
|Usual onset||2–14 days (typically 5) from exposure|
|Causes||Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)|
|Risk factors||Travel, viral exposure|
|Diagnostic method||rRT-PCR testing, CT scan|
|Prevention||Hand washing, quarantine, social distancing
Surgical masks are recommended by the WHO when taking care of an infected person, or if symptoms occur, to prevent the spread of disease. Other health authorities have different guidelines surrounding the use of masks to prevent COVID-19 infection.
|Treatment||Symptomatic and supportive|
|Frequency||1,429,437 confirmed cases|
|Deaths||82,074 (5.7% of confirmed cases)|
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified in December 2019 in Wuhan, the capital of China’s Hubei province, and has since spread globally, resulting in the ongoing 2019–20 coronavirus pandemic. Common symptoms include fever, cough and shortness of breath. Other symptoms may include fatigue, muscle pain, diarrhea, sore throat, loss of smell and abdominal pain. While the majority of cases result in mild symptoms, some progress to viral pneumonia and multi-organ failure. As of 8 April 2020, more than 1.42 million cases have been reported in more than 200 countries and territories, resulting in more than 82,000 deaths. More than 300,000 people have recovered.
The virus is mainly spread during close contact[a] and by small droplets produced when those infected cough, sneeze or talk. These droplets may also be produced during breathing; however, they rapidly fall to the ground or surfaces and are not generally spread through the air over large distances. People may also become infected by touching a contaminated surface and then their face. The virus can survive on surfaces for up to 72 hours. It is most contagious during the first three days after onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease. The time from exposure to onset of symptoms is typically around five days, but may range from two to 14 days. The standard method of diagnosis is by real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab. The infection can also be diagnosed from a combination of symptoms, risk factors and a chest CT scan showing features of pneumonia.
Recommended measures to prevent infection include frequent hand washing, social distancing (maintaining physical distance from others, especially from those with symptoms), covering coughs and sneezes with a tissue or inner elbow and keeping unwashed hands away from the face. The use of masks is recommended for those who suspect they have the virus and their caregivers. Recommendations for mask use by the general public vary, with some authorities recommending against their use, some recommending their use and others requiring their use. Currently, there is no vaccine or specific antiviral treatment for COVID-19. Management involves treatment of symptoms, supportive care, isolation and experimental measures.
The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 and a pandemic on 11 March 2020. Local transmission of the disease has been recorded in many countries across all six WHO regions.
Signs and symptoms
|Loss of smell||15 to 30|
|Shortness of breath||19|
|Muscle or joint pain||15|
|Nausea or vomiting||5|
|Diarrhoea||4 to 31|
Those infected with the virus may be asymptomatic or develop flu-like symptoms, including fever, cough, fatigue and shortness of breath. Emergency symptoms include difficulty breathing, persistent chest pain or pressure, confusion, difficulty waking and bluish face or lips; immediate medical attention is advised if these symptoms are present. Less commonly, upper respiratory symptoms, such as sneezing, runny nose or sore throat may be seen. Symptoms such as nausea, vomiting and diarrhoea have been observed in varying percentages. Some cases in China initially presented only with chest tightness and palpitations. In March 2020 there were reports indicating that loss of the sense of smell (anosmia) may be a common symptom among those who have mild disease, although not as common as initially reported. In some, the disease may progress to pneumonia, multi-organ failure and death. In those who develop severe symptoms, time from symptom onset to needing mechanical ventilation is typically eight days.
As is common with infections, there is a delay between the moment when a person is infected with the virus and the time when they develop symptoms. This is called the incubation period. The incubation period for COVID-19 is typically five to six days but may range from two to 14 days. 97.5% of people who develop symptoms will do so within 11.5 days of infection.
Reports indicate that not all who are infected develop symptoms, but their role in transmission is unknown. Preliminary evidence suggests asymptomatic cases may contribute to the spread of the disease. The proportion of infected people who do not display symptoms is currently unknown and being studied, with the Korea Centers for Disease Control and Prevention (KCDC) reporting that 20% of all confirmed cases remained asymptomatic during their hospital stay. China’s National Health Commission began including asymptomatic cases in its daily cases on 1 April, of the 166 infections on that day, 130 (78%) were asymptomatic.
Some details about how the disease is spread are still being determined. The WHO and the US Centers for Disease Control and Prevention (CDC) say it is primarily spread during close contact and by small droplets produced when people cough, sneeze or talk; with close contact being within 1–3 m (3 ft 3 in–9 ft 10 in). A study in Singapore found that an uncovered cough can lead to droplets travelling up to 4.5 meters (15 feet). A second study, produced during the 2020 pandemic, found that advice on the distance droplets could travel might be based on old 1930s research which ignored the protective effect and speed of the warm moist outbreath surrounding the droplets; it advised that droplets can travel around 7–8 metres.
Respiratory droplets may also be produced while breathing out, including when talking. Though the virus is not generally airborne, 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. The droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs. Some medical procedures such as intubation and cardiopulmonary resuscitation (CPR) may cause respiratory secretions to be aerosolised and thus result in airborne spread. It may also spread when one touches a contaminated surface, known as fomite transmission, and then touches ones eyes, nose or mouth. While there are concerns it may spread by feces, this risk is believed to be low.
The virus is most contagious when people are symptomatic; while spread may be possible before symptoms appear, this risk is low. 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.
The virus survives for hours to days on surfaces. Specifically, the virus was found to be detectable for one day on cardboard, for up to three days on plastic and stainless steel and for up to four hours on copper. This, however, varies based on the humidity and temperature. Surfaces may be decontaminated with a number of solutions (within one minute of exposure to the disinfectant to achieve a 4 or more log reduction), including 78–95% ethanol (alcohol used in spirits), 70–100% 2-propanol (isopropyl alcohol), the combination of 45% 2-propanol with 30% 1-propanol, 0.21% sodium hypochlorite (bleach), 0.5% hydrogen peroxide, or 0.23–7.5% povidone-iodine. Ordinary soap and detergent are also highly effective if correctly used; soap products attack the virus’ fatty protective layer, deactivating it, as well as freeing them from skin and other surfaces. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate (a surgical disinfectant), are less effective, as are products advertised as killing bacteria which have little effect on a virus.
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. All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature. Outside the human body, the virus is killed by household soap, which bursts its protective bubble.
SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have a zoonotic origin. Genetic analysis has revealed that 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). 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.
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. 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, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and that these hypotheses need to be tested. As the alveolar disease progresses, respiratory failure might develop and death may follow.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine.
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.
The WHO has published several testing protocols for the disease. The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test is typically done on respiratory samples obtained by a nasopharyngeal swab, however a nasal swab or sputum sample may also be used. Results are generally available within a few hours to two days. Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value. Chinese 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. As of 4 April 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. The FDA approved the first point-of-care test on 21 March 2020 for use at the end of that month.
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 in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count or reduced lymphocyte count.
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. Typical features on CT include bilateral multilobar ground-glass opacificities with a peripheral, asymmetric and posterior distribution. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling) and consolidation develop as the disease evolves. 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”.
- 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. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
- healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
- plasmocytosis in BAL
- Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
- Liver: microvesicular steatosis
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, practising good respiratory hygiene and avoiding touching the eyes, nose or mouth with unwashed hands. 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. They also recommend proper hand hygiene after any cough or sneeze. Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel and cancelling mass gatherings. Social distancing also includes that people stay at least 6 feet (1.8 m) apart.
As a vaccine is not expected until 2021 at the earliest, a key part of managing COVID-19 is trying to decrease the epidemic peak, known as “flattening the curve“. 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.
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. Some countries also recommend healthy individuals to wear face masks, including China, Hong Kong, Thailand, Czech Republic, and Austria. 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 masks increasing sixfold, N95 respirators tripled, and gowns doubled. Some health experts consider wearing non-medical grade masks and 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.
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 and avoid sharing personal household items. 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.
For areas where commercial hand sanitisers are not readily available, the 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.
People are managed with supportive care, which may include fluid therapy, oxygen support and supporting other affected vital organs. The CDC recommends that those who suspect they carry the virus wear a simple face mask. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.
The WHO and Chinese National Health Commission have published recommendations for taking care of people who are hospitalised with COVID-19. Intensivists and pulmonologists in the US have compiled treatment recommendations from various agencies into a free resource, the IBCC.
Some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use. The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms, and the FDA says currently there is no evidence that NSAIDs worsen COVID-19 symptoms.
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. Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.
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. For healthcare professionals caring for people with COVID-19, the CDC recommends placing the person in an Airborne Infection Isolation Room (AIIR) in addition to using standard precautions, contact precautions and airborne precautions.
CDC outlines the specific guidelines for the use of personal protective equipment (PPE) during the pandemic. The recommended gear includes:
When available, respirators (instead of facemasks) are preferred. N95 respirators are approved for industrial settings but the FDA has authorised the masks for use under an Emergency Use Authorisation (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. When masks are not available, the CDC recommends using face shields or, as a last resort, homemade masks.
Most cases of COVID-19 are not severe enough to require mechanical ventilation (artificial assistance to support breathing), but a percentage of cases do. Some Canadian doctors recommend the use of invasive mechanical ventilation because this technique limits the spread of aerosolised transmission vectors. Severe cases are most common in older adults (those older than 60 years and especially those older than 80 years). 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 hospitalisation. 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). One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died. Around 20–30% of the people in hospital with pneumonia from COVID-19 needed ICU care for respiratory support.
Acute respiratory distress syndrome
Mechanical ventilation becomes more complex as ARDS develops in COVID-19 and oxygenation becomes increasingly difficult. Ventilators capable of pressure control modes and high PEEP are needed to maximise oxygen delivery while minimising the risk of ventilator-associated lung injury and pneumothorax. High PEEP may not be available on older ventilators.