The virus is primarily spread between people during close contact,[lower-alpha ១] often via small droplets produced by coughing,[lower-alpha ២] sneezing, and talking.[៥][១៦][១៨] The droplets usually fall to the ground or onto surfaces rather than remaining in the air over long distances.[៥] People may also become infected by touching a contaminated surface and then touching their face.[៥][១៦] On surfaces, the amount of virus declines over time until it is insufficient to remain infectious, but it may be detected for hours or days.[៥][១៨][១៩] It is most contagious during the first three days after the onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease.[២០] The standard method of diagnosis is by real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.[២១]Chest CT imaging may also be helpful for diagnosis in individuals where there is a high suspicion of infection based on symptoms and risk factors; however, guidelines do not recommend using it for routine screening.[២២][២៣]
Recommended measures to prevent infection include frequent hand washing, maintaining physical distance from others (especially from those with symptoms), quarantine, covering coughs, and keeping unwashed hands away from the face.[២៤][២៥][៦] In addition, the use of a face covering is recommended for those who suspect they have the virus and their caregivers.[២៦][២៧] Recommendations for face covering use by the general public vary, with some authorities recommending, some recommending against, and others requiring their use.[២៧][២៨][២៩] There is limited evidence for or against the use of masks (medical or other) in healthy individuals in the wider community.[៥]
Fever is the most common symptom, although some older people and those with other health problems experience fever later in the disease.[៣][៣៥] In one study, 44% of people had fever when they presented to the hospital, while 89% went on to develop fever at some point during their hospitalization.[៣][៣៦]
A decreased sense of smell or disturbances in taste may occur.[៤៣][៤៤]Loss of smell was a presenting symptom in 30% of confirmed cases in South Korea.[១២][៤៥]
As is common with infections, there is a delay between the moment a person is first infected and the time he or she develops 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,[៤៦][៤៧] although 97.5% of people who develop symptoms will do so within 11.5 days of infection.[៤៨]
A minority of cases do not develop noticeable symptoms at any point in time.[៤៩][៥០] These asymptomatic carriers tend not to get tested, and their role in transmission is not yet fully known.[៥១][៥២] However, preliminary evidence suggests they may contribute to the spread of the disease.[៥៣][៥៤] In March 2020, the Korea Centers for Disease Control and Prevention (KCDC) reported that 20% of confirmed cases remained asymptomatic during their hospital stay.[៥៤][៥៥]
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.[៥៨][៥៩] 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.[៦០] Approximately 20-30% of people who present with COVID‑19 demonstrate elevated liver enzymes (transaminases).[៦១] Liver injury as shown by blood markers of liver damage is frequently seen in severe cases.[៦២]
COVID-19 is a new disease, and the ways it spreads between people are under investigation, including: the role of small droplets, the extent and how it may be transmitted through air, and how long the virus remains infectious on surfaces.[៥][១៦][១៨] The disease is spread during close contact, often by small droplets produced during coughing, sneezing, or talking.[៥][១៨] During close contact, (1 to 2 metres, 3 to 6 feet), people catch the disease after breathing in contaminated droplets that were exhaled by infected people. However, the droplets are relatively heavy and usually fall to the ground or surfaces, as opposed to being infectious over large distances.[៥][១៨]
After the droplets fall to floors or surfaces, they still can infect other people, if they touch contaminated surfaces and then their eyes, nose or mouth with unwashed hands.[៥] On surfaces the amount of active virus decreases over time until it can no longer cause infection.[១៨] However, experimentally, the virus can survive on various surfaces for some time, (for example copper or cardboard for a few hours, and plastic or steel for a few days).[១៨][៦៣] Surfaces are easily decontaminated with household disinfectants which kill the virus outside the human body or on the hands.[៥] Disinfectants or bleach are not a treatment for COVID-19, and cause health problems when not used properly, such as inside the human body.[៦៤]
The virus is most contagious during the first three days after onset of symptoms, although spread is known to occur up to two days before symptoms appear (presymptomatic transmission) and in later stages of the disease.[១៦][១៨][៦៦][៦៧] Some people have been infected and recovered without showing symptoms, but uncertainties remain in terms of asymptomatic transmission.[១៨]
Although COVID-19 is not a sexually transmitted infection, kissing, intimate contact, and faecal oral routes are suspected to transmit the virus.[៦៨][៦៩]
Severe acute respiratory syndrome coronavirus2 (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.[៧០] All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature.[៧១]
Outside the human body, the virus is killed by household soap, which bursts its protective bubble.[២២]
SARS-CoV-2 is closely related to the original SARS-CoV.[៧២] 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).[៤១] In February 2020, Chinese researchers found that there is only one amino acid difference in the binding domain of the S protein between the coronaviruses from pangolins and those from humans; however, whole-genome comparison to date found that at most 92% of genetic material was shared between pangolin coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.[៧៣]
Pathophysiology
The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in 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.[៧៤] 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,[៧៥][៧៦] though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and these hypotheses need to be tested.[៧៧] As the alveolar disease progresses, respiratory failure might develop and death may follow.[៧៦]
SARS-CoV-2 may also cause respiratory failure through affecting the brainstem as other coronaviruses have been found to invade the central nervous system (CNS). While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain.[៧៨][៧៩]
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system.[៨២] An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China,[៣៩] and is more frequent in severe disease.[៨៣] Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart.[៨២] ACE2 receptors are highly expressed in the heart and are involved in heart function.[៨២][៨៤] A high incidence of thrombosis (31%) and venous thromboembolism (25%) have been found in ICU patients with COVID‑19 infections and may be related to poor prognosis.[៨៥][៨៦] Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in patients infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia.[៨៧]
Another common cause of death is complications related to the kidneys[៨៧]—SARS-CoV-2 directly infects kidney cells, as confirmed in post-mortem studies. Acute kidney injury is a common complication and cause of death; this is more significant in patients with already compromised kidney function, especially in people with pre-existing chronic conditions such as hypertension and diabetes which specifically cause nephropathy in the long run.[៨៨]
Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.[៨៩]
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in COVID‑19 patients.[៩១] Lymphocytic infiltrates have also been reported at autopsy.[៨៩]
The WHO has published several testing protocols for the disease.[៩៣] The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR).[៩៤] The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used.[២១][៩៥] Results are generally available within a few hours to two days.[៩៦][៩៧] Blood tests can be used, but these require two blood samples taken two weeks apart, and the results have little immediate value.[៩៨] 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.[៩][៩៩][១០០] As of 4 មេសា 2020[update], 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.[១០១][១០២][១០៣] The Chinese experience with testing has shown the accuracy is only 60 to 70%.[១០៤] The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.[១០៥]
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.[១០៦]
A study asked hospitalised COVID‑19 patients to cough into a sterile container, thus producing a saliva sample, and detected the virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).[៦៥]
Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening.[២២][២៣] Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection.[២២] Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.[២២][១០៧]
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.[១០៨]
Progressively stronger mitigation efforts to reduce the number of active cases at any given time—known as "flattening the curve"—allows healthcare services to better manage the same volume of patients.[១១៤][១១៥][១១៦] Likewise, progressively greater increases in healthcare capacity—called raising the line—such as by increasing bed count, personnel, and equipment, helps to meet increased demand.[១១៧]Mitigation attempts that are inadequate in strictness or duration—such as premature relaxation of distancing rules or stay-at-home orders—can allow a resurgence after the initial surge and mitigation.[១១៥][១១៨]
Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places, keeping distance from others, 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.[១១៩][១២០][១២១] 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.[១១៩] Proper hand hygiene after any cough or sneeze is encouraged.[១១៩] The CDC has recommended the use of cloth face coverings in public settings where other social distancing measures are difficult to maintain, in part to limit transmission by asymptomatic individuals.[១២២] The U.S. National Institutes of Health guidelines do not recommend any medication for prevention of COVID‑19, before or after exposure to the SARS-CoV-2 virus, outside of the setting of a clinical trial.[១២៣]
Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel, and cancelling large public gatherings.[១២៤] Distancing guidelines also include that people stay at least 6 feet (1.8 m) apart.[១២៥] There is no medication known to be effective at preventing COVID‑19.[១២៦] After the implementation of social distancing and stay-at-home orders, many regions have been able to sustain an effective transmission rate ("Rt") of less than one, meaning the disease is in remission in those areas.[១២៧] In a simple model needs on average over time be kept at or below zero to avoid exponential growth.[ត្រូវការអំណះអំណាង]
As a vaccine is not expected until 2021 at the earliest,[១២៨] a key part of managing COVID‑19 is trying to decrease and delay the epidemic peak, known as "flattening the curve".[១១៥] 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.[១១៥][១១៨]
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.[២៦][១៣៦] 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.[១១៩]
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.[១៣៧]
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.
ការគ្រប់គ្រង
People are managed with supportive care, which may include fluid therapy, oxygen support, and supporting other affected vital organs.[១៣៨][១៣៩][១៤០] The CDC recommends that those who suspect they carry the virus wear a simple face mask.[២៦]Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.[៣៦][១៤១] Personal hygiene and a healthy lifestyle and diet have been recommended to improve immunity.[១៤២] Supportive treatments may be useful in those with mild symptoms at the early stage of infection.[១៤៣]
Per the World Health Organization, as of April 2020, there is no specific treatment for COVID‑19.[៥] On May 1, 2020, the United States gave Emergency Use Authorization (not full approval) for remdesivir in people hospitalized with severe COVID-19 after a study suggested it reduced the duration of recovery.[៣០][១៤៨] Researchers continue working on more effective treatments and many vaccine candidates are in development or testing phases.
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.[១២៣][១៥៤][១៥៥][១៥៦] One study from April 22 found that people with COVID-19 and hypertension had lower all-cause mortality when on these medications.[១៥៧]
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.[១៦៣] 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.[១៦៤]
When available, respirators (instead of facemasks) are preferred.[១៦៧] 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.[១៦៨] When masks are not available, the CDC recommends using face shields or, as a last resort, homemade masks.[១៦៩]
Mechanical ventilation
Most cases of COVID‑19 are not severe enough to require mechanical ventilation or alternatives, but a percentage of cases are.[១៧០][១៧១] The type of respiratory support for individuals with COVID‑19 related respiratory failure is being actively studied for people in the hospital, with some evidence that intubation can be avoided with a high flow nasal cannula or bi-level positive airway pressure.[១៧២] Whether either of these two leads to the same benefit for people who are critically ill is not known.[១៧៣] Some doctors prefer staying with invasive mechanical ventilation when available because this technique limits the spread of aerosol particles compared to a high flow nasal cannula.[១៧០]
Severe cases are most common in older adults (those older than 60 years,[១៧០] and especially those older than 80 years).[១៧៤] 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.[១៧៥] This limited capacity is a significant driver behind calls to flatten the curve.[១៧៥] One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died.[៣៦] In China, approximately 30% of people in hospital with COVID‑19 are eventually admitted to ICU.[៣]
Research into potential treatments started in January 2020,[១៧៩] and several antiviral drugs are in clinical trials.[១៨០][១៨១]Remdesivir appears to be the most promising.[១២៦] Although new medications may take until 2021 to develop,[១៨២] several of the medications being tested are already approved for other uses or are already in advanced testing.[១៨៣] Antiviral medication may be tried in people with severe disease.[១៣៨] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[១៨៤]
The FDA has granted temporary authorisation to convalescent plasma as an experimental treatment in cases where the person's life is seriously or immediately threatened. It has not undergone the clinical studies needed to show it is safe and effective for the disease.[១៨៥][១៨៦][១៨៧]
In February 2020, China launched a mobile app to deal with the disease outbreak.[១៨៨] Users are asked to enter their name and ID number. The app can 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.[១៨៩]
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.[១៩០][១៩១] 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.[១៩២] Also in March 2020, Deutsche Telekom shared aggregated phone location data with the German federal government agency, Robert Koch Institute, to research and prevent the spread of the virus.[១៩៣] Russia deployed facial recognition technology to detect quarantine breakers.[១៩៤] 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".[១៩៥] German government conducted a 48 hours weekend hackathon with more than 42.000 participants.[១៩៦][១៩៧] Two million people in the UK used an app developed in March 2020 by King's College London and Zoe to track people with COVID‑19 symptoms.[១៩៨] Also, the president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of coronavirus.[១៩៩]
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.[២០០][២០១]
The Lancet published a 14-page call for action focusing on the UK and stated conditions were such that a range of mental health issues was likely to become more common. BBC quoted Rory O'Connor in saying, "Increased social isolation, loneliness, health anxiety, stress, and an economic downturn are a perfect storm to harm people's mental health and wellbeing."[២០២][២០៣]
Prognosis
This article relies on references to primary sources or sources affiliated with the subject, rather than references from independent authors and third-party publications. Please add more appropriate citations from reliable sources.(March 2020)
The severity of diagnosed COVID-19 cases in China[២០៤]
Case fatality rate in China depending on other health problems. Data through 11 February 2020.[២០៥]
The number of deaths vs total cases by country and approximate case fatality rate[២០៩]
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.[៤១]
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years.[១៨] They 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%.[២១០][២១១][២១២]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.[២១៣][២១៤] In China, children acquired infections mainly through close contact with their parents or other family members who lived in Wuhan or had traveled there.[២១០]
Most of those who die of COVID‑19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease.[២១៦] 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.[២១៧] According to the same report, the median time between the 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 hospitalisation and death.[២១៧] 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.[២១៨] 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%.[២១៩]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).[៤១] 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.[៤២] According to March data from the United States, 89% of those hospitalised had preexisting conditions.[២២០]
The availability of medical resources and the socioeconomics of a region may also affect mortality.[២២១] Estimates of the mortality from the condition vary because of those regional differences,[២២២] but also because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be overestimated.[២២៣] However, the fact that deaths are the result of cases contracted in the past can mean the current mortality rate is underestimated.[២២៤][២២៥] Smokers were 1.4 times more likely to have severe symptoms of COVID‑19 and approximately 2.4 times more likely to require intensive care or die compared to non-smokers.[២២៦]
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.[២២៧] This may also lead to post-intensive care syndrome following recovery.[២២៨]
Case fatality rates (%) by age and country or US state
Total infection fatality rate is estimated to be 0.66% (0.39–1.3). Infection fatality rate is fatality per all infected individuals, regardless of whether they were diagnosed or had any symptoms. Numbers in parentheses are 95% credible intervals for the estimates.
ភាពស៊ាំ
It is unknown (as of April 2020) if past infection provides effective and long-term immunity in people who recover from the disease.[២៤៦][២៤៧] Some of the infected have been reported to develop protective antibodies, so acquired immunity is presumed likely, based on the behaviour of other coronaviruses.[២៤៨] However, cases in which recovery from COVID‑19 was followed by positive tests for coronavirus at a later date have been reported.[២៤៩][២៥០][២៥១][២៥២] These cases are believed to be lingering infection rather than reinfection,[២៥២] or false positives due to remaining RNA fragments.[២៥៣] Some other coronaviruses circulating in people are capable of reinfection after roughly a year.[២៥៤][២៥៥]
The virus is thought to be natural and has an animal origin,[៧១] through spillover infection.[២៥៦] The actual origin is unknown, but the first known cases of infection happened in China. By December 2019, the spread of infection was almost entirely driven by human-to-human transmission.[២០៥][២៥៧] 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 1December 2019.[២៥៨][២៥៩][២៦០] Official publications from the WHO reported the earliest onset of symptoms as 8December 2019.[២៦១] Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020.[២៦២][២៦៣]
Several measures are commonly used to quantify mortality.[២៦៤] These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health.[២៦៥]
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 ២% (២២៦៥៥៥៩/១០៤៣៣៣៨៧៨) as of ៤ កុម្ភៈ ២០២១.[៧] The number varies by region.[២៦៦]
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. Many academics have attempted to calculate these numbers for specific populations.[២៦៧]
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing.[២៦៨] In the United States, the prisoner population is aging and many of them are at high risk for poor outcomes from COVID-19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.[២៦៨]
Total confirmed cases over time
Total deaths over time
Total confirmed cases of COVID‑19 per million people[២៦៩]
Total confirmed deaths due to COVID‑19 per million people[២៧០]
Infection fatality rate
Our World in Data states that as of March 25, 2020, the infection fatality rate (IFR) cannot be accurately calculated.[២៧១] In February, the World Health Organization estimated the IFR at 0.94%, with a confidence interval between 0.37 percent to 2.9 percent.[២៧២] The University of OxfordCentre for Evidence-Based Medicine (CEBM) estimated a global CFR of 0.72 percent and IFR of 0.1 percent to 0.36 percent.[២៧៣] According to CEBM, random antibody testing in Germany suggested an IFR of 0.37% (0.12% to 0.87%) there, but there have been concerns about false positives.[២៧៣][២៧៤][២៧៥] Firm lower limits of infection fatality rates have been established in a number of locations. In New York City, with a population of 8.4 million, as of April 25, 16,673 (0.20% of the population) have died from COVID-19, and 20,800 (0.25% of the population) excess deaths have occurred, and in Bergamo province, where 0.57% of the population has died.[២៧៦][២៧៧][២៧៨] To get a better view on the number of people infected initial antibody testing have been carried out, but there are no valid scientific reports based on any of them as of yet.[២៧៩][២៨០]
The impact of the pandemic and its mortality rate are different for men and women.[២៨១] Mortality is higher in men in studies conducted in China and Italy.[១][២៨២][២៨៣] The higher risk for men appears in their 50s, and begins to taper off only at 90.[២៨៣] In China, the death rate was 2.8 percent for men and 1.7 percent for women.[២៨៣] The exact reasons for this sex-difference are not known, but genetic and behavioural factors could be a reason.[២៨១] Sex-based immunological differences, a lower prevalence of smoking in women, and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men.[២៨៣] In Europe, of those infected with COVID‑19, 57% were men; of those infected with COVID‑19 who also died, 72% were men.[២៨៤] As of April 2020, the U.S. government is not tracking sex-related data of COVID‑19 infections.[២៨៥] Research has shown that viral illnesses like Ebola, HIV, influenza, and SARS affect men and women differently.[២៨៥] A higher percentage of health workers, particularly nurses, are women, and they have a higher chance of being exposed to the virus.[២៨៦] School closures, lockdowns, and reduced access to healthcare following the 2019–20 coronavirus pandemic may differentially affect the genders and possibly exaggerate existing gender disparity.[២៨១][២៨៧]
Ethnic differences
In the U.S., a greater proportion of deaths due to COVID-19 have occurred among African Americans.[២៨៨] Structural factors that prevent African Americans from practicing social distancing include their concentration in crowded substandard housing and "essential" occupations such as public transit employees and health-care workers. Greater prevalence of lacking health insurance and care and of underlying conditions such as diabetes, hypertension and heart disease also increase their risk of death.[២៨៩] Similar issues affect Native American and Latino communities.[២៨៨] Leaders have called for efforts to research and address the disparities.[២៩០]
Existing respiratory problems
When someone with existing respiratory problems is infected with COVID-19, they are at greater risk for severe symptoms.[២៩១] COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.[២៩២]
សង្គម និង វប្បធម៌
ឈ្មោះ
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus",[២៩៣][២៩៤][២៩៥] with the disease sometimes called "Wuhan pneumonia".[២៩៦][២៩៧] In the past, many diseases have been named after geographical locations, such as the Spanish flu,[២៩៨]Middle East Respiratory Syndrome, and Zika virus.[២៩៩]
In January 2020, the World Health Organisation recommended 2019-nCov[៣០០] and 2019-nCoV acute respiratory disease[៣០១] as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species or groups of people in disease and virus names to prevent social stigma.[៣០២][៣០៣][៣០៤]
The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020.[៣០៥] WHO chief Tedros Adhanom Ghebreyesus explained: CO for corona, VI for virus, Dfor disease and 19 for when the outbreak was first identified (31 December 2019).[៣០៦] The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications.[៣០៥] Both the disease and virus are commonly referred to as "coronavirus" in the media and public discourse.
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.[៣០៧][៣០៨][៣០៩]
Decreased emergency room use
In Austria, 39% fewer persons sought help for cardiac symptoms in the month of March. A study estimated that there were 110 incidents of preventable cardiac death as compared to 86 confirmed deaths from Coronavirus as of March 29.[៣១០]
A preliminary study in the U.S. found 38% under-utilization of cardiac care units as compared to normal.[៣១១] The head of cardiology at the University of Arizona has stated, "My worry is some of these people are dying at home because they're too scared to go to the hospital."[៣១២] There is also concern that persons with symptoms of stroke and appendicitis are delaying seeking help.[៣១២][៣១៣]
សត្វផ្សេងៗ
Humans appear to be capable of spreading the virus to some other animals. A domestic cat in Liège, Belgium, tested positive after it started showing symptoms (diarrhoea, vomiting, shortness of breath) a week later than its owner, who was also positive.[៣១៤]Tigers at the Bronx Zoo in New York, United States, tested positive for the virus and showed symptoms of COVID‑19, including a dry cough and loss of appetite.[៣១៥]Minks at two farms in the Netherlands also tested positive for COVID-19.[៣១៦]
A study on domesticated animals inoculated with the virus found that cats and ferrets appear to be "highly susceptible" to the disease, while dogs appear to be less susceptible, with lower levels of viral replication. The study failed to find evidence of viral replication in pigs, ducks, and chickens.[៣១៧]
No medication or vaccine is approved to treat the disease.[១៨៣] International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers.[៣១៨][៣១៩] In March, the World Health Organisation initiated the "SOLIDARITY Trial" to assess the treatment effects of four existing antiviral compounds with the most promise of efficacy.[៣២០]
There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand. To minimise the impact of misinformation, medical professionals and the public are advised to expect rapid changes to available information, and to be attentive to retractions and other updates.[៣២១]
There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous work on SARS-CoV is being used because both SARS-CoV and SARS-CoV-2 use the ACE2 receptor to enter human cells.[៣២២] Three vaccination strategies are 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.[៣២៣]
On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle, United States. The vaccine contains a harmless genetic code copied from the virus that causes the disease.[៣២៤]
Antibody-dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.[៣២៥]
At least 29 phase II–IV efficacy trials in COVID‑19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China.[៣២៦][៣២៧] There are more than 300 active clinical trials underway as of April 2020.[១២៦] Seven trials were evaluating already approved treatments, including four studies on hydroxychloroquine or chloroquine.[៣២៧] 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.[៣២៦][៣២៧] Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinantangiotensin-converting enzyme 2.[៣២៧]
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.[៣២៨][៣២៩]
In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness.[៣៣៦]Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.[៣៣៤]
There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID‑19, with some studies showing little or no improvement.[៣៣៧][៣៣៨] The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.[១២៦]
Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID‑19 treatment.[១២៦]
Anti-cytokine storm
Cytokine release syndrome (CRS) can be a complication in the later stages of severe COVID‑19. There is preliminary evidence that hydroxychloroquine may have anti-cytokine storm properties.[៣៣៩]
Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed.[៣៤០][៣៤១] It is undergoing a phase2 non-randomised trial at the national level in Italy after showing positive results in people with severe disease.[៣៤២][៣៤៣] 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.[៣៤៤][៣៤៥][១៣] The interleukin-6receptor antagonist was approved by the FDA to undergo a phase III clinical trial assessing the medication's impact on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, CAR T celltherapy, in 2017.[៣៤៦] To date, there is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the blood-brain barrier, and exacerbating neurotoxicity while having no impact on the incidence of CRS.[៣៤៧]
Lenzilumab, an anti-GM-CSF monoclonal antibody, is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T-cells in hospitalised patients with COVID‑19.[៣៤៨]
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.[៣៥០] This strategy was tried for SARS with inconclusive results.[៣៥០]Viral neutralisation 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.[៣៥០] Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development.[៣៥០] 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.[៣៥១]
↑Close contact is defined as one metre (three feet) by the WHO[៥] and two metres (six feet) by the CDC.[១៦]
↑An uncovered cough can travel up to 8.2 ម៉ែត្រs (27 feet).[១៧]
ឯកសារយោង
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