As is common with infections, there is a delay from when a person is infected with the virus to when they develop symptoms, known as the incubation period. The incubation period for COVID-19 is typically five to six days but may range from two to fourteen days.
The disease is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously referred to as the 2019 novel coronavirus (2019-nCoV). It is primarily spread between people via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel. SARS-CoV-2 can last up to three days, or in aerosols for three hours. The virus has also been found in faeces, but as of March 2020 it is unknown whether transmission through faeces is possible, and the risk is expected to be low.
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 "spike", 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 is thought to be natural and have an animal origin, through spillover infection. It was first transmitted to humans in Wuhan, China, in November or December 2019, and the primary source of infection became human-to-human transmission by early January 2020. The earliest known infection occurred on 17 November 2019. As of 14 March 2020, 67,790 cases and 3,075 deaths due to the virus have been reported in Hubei province; a case fatality rate (CFR) of 4.54%.
Microscopy image showing SARS-CoV-2. The spikes on the outer edge of the virus particles resemble a crown, giving the disease its characteristic name.
Schematic diagram of the Coronavirus particle. S, spike protein; M, membrane protein, E, envelope protein; N, nucleocapsid protein; ; structural proteins of coronavirusCoronavirus virion structure.
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 can be done on respiratory samples obtained by various methods, including a nasopharyngeal swab or sputum sample. 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 26 February 2020, there were no antibody tests or point-of-care tests though efforts to develop them are ongoing.
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 study published by a team at the Tongji Hospital in Wuhan on 26 February 2020 showed that a chest CT scan for COVID-19 has greater sensitivity (98%) than the polymerase chain reaction (71%). False negative results may occur due to PCR kit failure, or due to either issues with the sample or issues performing the test. False positive results are likely to be rare.
One study in China found that CT scans showed ground-glass opacities in 56%, but 18% had no radiological findings. Bilateral and peripheral ground glass opacities are the most typical CT findings, though they are non-specific.Consolidation, linear opacities and reverse halo sign are other radiological findings. Initially, the lesions are confined to one lung, but as the disease progresses, indications manifest in both lungs in 88% of so-called "late patients" in the study group (the subset for whom time between onset of symptoms and chest CT was 6–12 days). Ground glass opacities are also a common feature in children's disease.
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.
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 epidemic 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 provides more time for a vaccine and treatment to be developed.
Preventive measures to reduce the chances of infection in locations with an outbreak of the disease are similar to those published for other coronaviruses: stay home, avoid travel and public activities, wash hands with soap and warm water often and for at least 20 seconds (proper hand hygiene and also the time it takes to sing "Happy Birthday to You" twice.), practice good respiratory hygiene and avoid touching the eyes, nose, or mouth with unwashed hands. The Centers for Disease Control and Prevention (CDC) in the United States recommends covering up the mouth and nose with a tissue during any cough or sneeze and coughing or sneezing into 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 6 feet apart (about 1.80 meters), roughly the length of a full size bed/mattress.
According to the WHO, the use of masks is only recommended if a person is coughing or sneezing or when one is taking care of someone with a suspected infection.
To prevent transmission of the virus, CDC recommends that infected individuals stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask when exposed to an individual or location of a suspected infection, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items. 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 recommended using an alcohol-based hand sanitizer with at least 60% alcohol, but only when soap and water are not readily available. For remote areas where commercial hand sanitizers are not readily available, WHO suggested two formulations for the local production. In both of these formulations the antimicrobial activity of ethanol or isopropanol is enhanced by low concentration of hydrogen peroxide while glycerol acts as a humectant. The WHO advises individuals to avoid touching the eyes, nose, or mouth with unwashed hands. Spitting in public places also should be avoided.
Four steps to putting on personal protective equipment
Management of people infected by the virus includes taking precautions while applying therapeutic manoeuvres, especially when performing procedures like intubation or hand ventilation that can generate aerosols.
Most cases of COVID-19 are not severe enough to require mechanical ventilation (artificial assistance to support breathing), but a percentage of cases do. This is 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. An Italian startup employed 3D printing technology to produce valves for life-saving coronavirus treatment due to a broken supply chain of original manufacturing. 3D printed valves costed $1 instead of $11,000 and were ready overnight.
No medication 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 patients 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 private cellphone data with the 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 "40% of people are continuing to move around anyway", as he is been informed by mobile phone operators.
Infected 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 COVID19 cases in China
Case fatality rates by age group in China. Data through 11 February 2020.
Case fatality rate depending on other health problems
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 disease 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 of all ages are susceptible to the disease, but are likely to have milder symptoms and a much 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 are at particular risk for severe infection.
In some patients 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.
Many of those who die of COVID-19 have preexisting conditions, including hypertension, diabetes mellitus, and cardiovascular disease. The Italian Istituto Superiore di Sanità reported that, out of over 2000 deaths from the disease in the country, 99.8% had at least one preexisting condition with the average patient having 2.7. According to the same report, the median time between onset of symptoms and death was eight days with a difference of one day between patients who were been[clarification needed] treated in an ICU compared to those who were not. 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. 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%.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). 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.
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 time lag in death occurring can mean the 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.
The case fatality rate (CFR) depends on the availability of healthcare, the typical age and health problems within the population, and the number of undiagnosed cases. Preliminary research has yielded case fatality rate numbers between 2% and 3%; in January 2020 the WHO suggested that the case fatality rate was approximately 3%, and 2% in February 2020 in Hubei. Other CFR numbers, which adjust for differences in time of confirmation, death or remission but are not peer reviewed, are respectively 7% and 33% for people in Wuhan 31 January. An unreviewed preprint of 55 deaths noted that early estimates of mortality may be too high as asymptomatic infections are missed. They estimated a mean infection fatality ratio (IFR, the mortality among infected) ranging from 0.8% to 0.9%. The outbreak in 2019–2020 has caused at least 244,517edit confirmed infections and 10,030edit deaths.
The epidemic spreads faster where people are close together and/or travel to other areas. Researchers found that travel restrictions can reduce the basic reproduction number from 2.35 to 1.05, allowing the epidemic to be manageable.
An observational study of nine people found no vertical transmission from mother to the newborn. Also, a descriptive study in Wuhan found no evidence of viral transmission through vaginal sex (from female to partner), but authors note that transmission during sex might occur through other routes.
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, 20 March 2020
The World Health Organization announced on 11 February 2020 that "COVID-19" would be the official name of the disease. World Health Organization chief Tedros Adhanom Ghebreyesus said "co" stands for "corona", "vi" for "virus" and "d" for "disease", while "19" was for the year, as the outbreak was first identified on 31 December 2019. Tedros said 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.
While the disease is named COVID-19, the virus that causes it is named severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. The virus was initially referred to as the 2019 novel coronavirus or 2019-nCoV. The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.
Because of its key role in the transmission and progression of the disease, ACE2 has been the focus of a significant proportion of research and various therapeutic approaches have been suggested.
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 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 being studied in China in February 2020, with positive preliminary results. Chloroquine and hydroxychloroquine effectively inhibit SARS-CoV-2 in vitro, with hydroxychloroquine proving to be more potent than chloroquine and with a more tolerable safety profile. Preliminary results from a trial suggested that chloroquine is effective and safe in treating COVID-19 associated pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course". However, there are calls for more review of the research to date. 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 patient’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.
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. 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. On 17 March, Chinese officials suggested the drug had been effective in treating COVID in Wuhan and Shenzhen.
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.
Using blood donations from people who have recovered from COVID-19 is being investigated, a strategy that was tried for SARS. The mechanism of action is that the antibodies produced by the immune systems of those who have already recovered are transferred to people in need of them via a nonvaccine form of immunization. Other forms of passive antibody therapy, such as with manufactured monoclonal antibodies, are in development. Convalescent serum production could be increased for quicker deployment.
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