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.
The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is primarily spread between people during close contact and via respiratory droplets from coughs and sneezes. A study investigating the rate of decay of the virus found no viable viruses after four hours on copper, 24 hours on cardboard, 72 hours on stainless steel, and 72 hours on plastic. However, detection rates did not reach 100% and varied between surface type (limit of detection was 3.33×100.5TCID50 per liter of air for aerosols, 100.5 TCID50 per milliliter of medium for plastic, steel, and cardboard, and 101.5 TCID50 per milliliter of medium for copper). Estimation of the rate of decay with a Bayesian regression model suggests that viruses may remain viable up to 18 hours on copper, 55 hours on cardboard, 90 hours on stainless steel, and over 100 hours on plastic. The virus remained viable in aerosols throughout the time of the experiment (three hours). The virus has also been found in faeces, and transmission through faeces is being researched.
The disease spreads faster where people are close together or travel between areas. Travel restrictions can reduce the basic reproduction number from 2.35 to 1.05, allowing the epidemic to be more manageable.
The virus has been found in the faeces of as many as 53% of hospitalised people and more anal swab positives have been found than oral swab positives in the later stages of infection. The virus was found in faeces from one to twelve days, and seventeen percent of patients continued to present the virus in faeces after no longer presenting them in respiratory samples, indicating that the viral gastrointestinal infection and the potential fecal-oral transmission can last even after viral clearance in the respiratory tract. Reoccurrence of the virus has also been detected through anal swabs suggesting a shift from more oral positive during the early stages of the disease to more anal positive during later periods.
Microscopy image showing SARS-CoV-2. The spikes on the outer edge of the virus particles resemble a crown, giving the virus its characteristic name.
Schematic diagram of the coronavirus particle. S, spike protein; M, membrane protein; E, envelope protein; N, nucleocapsid protein; structural proteins of coronavirus. Coronavirus virion structure.
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 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 that laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus. As of 19 March 2020, there were no antibody tests though efforts to develop them are ongoing. 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.
An illustration of the effect of spreading out infections over a long period of time, known as flattening the curve; decreasing peaks allows healthcare services to better manage the same volume of patients.
Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places, washing hands with soap and warm water often and for at least 20 seconds, practicing 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 canceling mass gatherings. Social distancing also includes that people stay at least six feet apart (about 1.80 meters).
Because a vaccine against SARS-CoV-2 is not expected to become available until 2021 at the earliest, a key part of managing the COVID-19 pandemic is trying to decrease the epidemic peak, known as "flattening the curve," through various measures seeking to reduce the rate of new infections. Slowing the infection rate helps decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until therapeutics 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, particularly China,Hong Kong and Thailand. 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 sanitizer with at least 60% alcohol, but only when soap and water are not readily available.
For areas where commercial hand sanitizers 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.
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.
Precautions must be taken to minimize the risk of virus transmission, especially in healthcare settings when performing procedures that can generate aerosols, such as intubation or hand ventilation.
When available, respirators (instead of facemasks) are preferred. N95 respirators are approved for industrial settings but the FDA has authorized 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. 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 aerosolized 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 hospitalization. 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 COVID19 needed ICU care for respiratory support. A number of organizations are using 3D printing to produce various needed equipment.
No medications are approved to treat the disease by the WHO although some are recommended by individual national medical authorities. Research into potential treatments started in January 2020, and several antiviral drugs are in clinical trials. Although new medications may take until 2021 to develop, several of the medications being tested are already approved for other uses, or are already in advanced testing. Antiviral medication may be tried in people with severe disease. The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.
In February 2020, China launched a mobile app to deal with the disease outbreak. 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.
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. 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. 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. Russia deployed facial recognition technology to detect quarantine breakers. Italian regional health commissioner Giulio Gallera said that he has been informed by mobile phone operators that "40% of people are continuing to move around anyway". German government conducted a 48 hours weekend hackathon with more than 42.000 participants. Also the president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of coronavirus.
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.
The severity of diagnosed COVID-19 cases in China
Case fatality rates by age group in China. Data through 11 February 2020.
Case fatality rate in China depending on other health problems. Data through 11 February 2020.
The number of deaths vs total cases by country and approximate case fatality rate
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.
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%.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.
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. 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. Liver injury as shown by blood markers of liver damage is frequently seen in severe cases.
Availability of medical resources and the socioeconomics of a region may also affect mortality. Estimates of the mortality from the condition vary because of those regional differences, but also because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be overestimated. However, the fact that deaths are the result of cases contracted in the past can mean the current mortality rate is underestimated.
It is unknown if past infection provides effective and long-term immunity in people who recover from the disease. Immunity is likely, based on the behaviour of other coronaviruses, but cases in which recovery from COVID-19 have been followed by positive tests for coronavirus at a later date have been reported. It is unclear if these cases are the result of reinfection, relapse, or testing error.
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.
Several measures are commonly used to quantify mortality. 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.
The death-to-case ratio reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on WHO statistics, the global death-to-case ratio was 4.7% (29,957 / 634,835) as of 29 March[update]. The number varies by region.
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.
Total confirmed cases over time
Total deaths over time
Total confirmed cases of COVID-19 per million people, 20 March 2020
Total confirmed deaths due to COVID-19 per million people, 24 March 2020
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 the year that the outbreak was first identified; 31 December 2019. The name had been chosen to avoid references to a specific geographical location (i.e. China), animal species, or group of people, in line with international recommendations for naming aimed at preventing stigmatisation.
In February 2020, the World Health Organization advised the public to not refer to Coronavirus as the "Chinese virus" or "Wuhan virus". Even more controversial terms, such as "Wuflu" and "Kung Flu", also emerged in the United States during this period (outside the community of medical professionals) as offensive ways of describing COVID-19. These terms are linked to Wuhan, where the virus was first detected, or China in general, via portmanteau with terms from traditional Chinese Martial Arts, Wushu and Kung Fu. Use of these terms (popularized 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. It also implies that the pandemic is China's aggressive gift to the world, when actually thousands of Chinese suffered and died from COVID-19, especially in Wuhan.
Because of its key role in the transmission and progression of SARS-CoV-2, ACE2 has been the focus of a significant proportion of research and various therapeutic approaches have been suggested. Personal hygiene, and a healthy lifestyle and diet have been recommended to improve immunity.
There is no available vaccine, but research into developing a vaccine has been undertaken by various agencies. Previous work on SARS-CoV is being utilised because SARS-CoV-2 and SARS-CoV both use the ACE2 receptor to enter human cells. 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.
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.
Chloroquine, previously used to treat malaria, was studied in China in February 2020, with positive preliminary results. However, there are calls for peer review of the research. 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.
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. Korean and Chinese Health Authorities recommend the use of chloroquine. 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. As of 20 March 2020[update], the treatment has not yet been approved by the U.S. Food and Drug Administration.
In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness.Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.
Studies have demonstrated that initial spike protein priming by transmembrane protease serine2 (TMPRSS2) is essential for entry of SARS-CoV-2 via interaction with the ACE2 receptor. 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.
Cytokine storm, a life-threatening medical condition, can be a complication in the later stages of severe COVID-19. There is evidence that hydroxychloroquine has anti-cytokine storm properties.
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