Main article: Severe acute respiratory syndrome coronavirus 2Severe 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. Blockade of the IL-6 system is recommended by Australasian Society for Immunology and Allergy to be considered early in severe disease, and is included for consideration in a number of national guidelines. 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%. 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. A higher percentage of health workers, particularly nurses, are women, and they have a higher chance of being exposed to the virus. During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". 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. Combined with a serum ferritin blood test to identify a cytokine storm (also called cytokine storm syndrome, not to be confused with cytokine release syndrome), it is meant to counter such developments, which are thought to be the cause of death in some affected people.
Forty - Coronavirus disease 2019
Infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2
Recommended measures to prevent infection include frequent hand washing, maintaining physical distance from others (especially from those with symptoms), quarantine (especially for those with symptoms), covering coughs, and keeping unwashed hands away from the face. In addition, the use of a face covering is recommended for those who suspect they have the virus and their caregivers. Recommendations for face covering use by the general public vary, with some authorities recommending for them, some recommending against them (to conserve masks for healthcare workers), and others requiring their use.
Fever is the most common symptom, although some older people and those with other health problems experience fever later in the disease.[unreliable medical source?] 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. A lack of fever does not verify someone is disease free.
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 average incubation period for COVID‑19 is five to six days but commonly ranges from one to 14 days, with approximately 10% of cases exceeding that time.
A minority of cases do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested, and their role in transmission is not yet fully known. However, preliminary evidence suggests they may contribute to the spread of the disease.
COVID-19 spreads mainly when people are in close contact (two metres or six feet) via small droplets produced during coughing, sneezing, or talking. Contaminated droplets exhaled by infected people are then inhaled into the lungs, or settle on other people's faces to cause new infection. The droplets are relatively heavy, usually fall to surfaces, and do not travel far through the air. People can transmit the virus without showing symptoms, but it is unclear how often this happens. One estimate of the number of those infected who are asymptomatic is 40%.
People are most infectious when they show symptoms (even mild or non-specific symptoms), but may be infectious for up to two days before symptoms appear (pre-symptomatic transmission). They remain infectious an estimated seven to twelve days in moderate cases and an average of two weeks in severe cases.
When the contaminated droplets fall to floors or surfaces they can, though less commonly, remain infectious if people touch contaminated surfaces and then their eyes, nose or mouth with unwashed hands. On surfaces the amount of active virus decreases over time until it can no longer cause infection, and surfaces are thought not to be the main way the virus spreads. It is unknown what amount of virus on surfaces is required to cause infection via this method, but it can be detected for up to four hours on copper, up to one day on cardboard, and up to three days on plastic (polypropylene) and stainless steel (AISI 304). Surfaces are easily decontaminated with household disinfectants which kill the virus outside the human body or on the hands. Disinfectants or bleach are not a treatment for COVID‑19, and cause health problems when not used properly, such as when used inside the human body.
COVID‑19 is a new disease, and many of the details of its spread are still under investigation. It spreads easily between people—easier than influenza but not as easily as measles. Estimates of the number of people infected by one person with COVID-19 (the R0) have varied widely. The WHO's initial estimates of the R0 were 1.4-2.5 (average 1.95), however a more recent review found the basic R0 (without control measures) to be higher at 3.28 and the median R0 to be 2.79.
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. 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 an animal (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 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.
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.[unreliable medical source?]
Another common cause of death is complications related to the kidneys.[better source needed] Early reports show that up to 30% of hospitalized patients in both China and New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.[unreliable medical source?]
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. Lymphocytic infiltrates have also been reported at autopsy.[unreliable medical source?]
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 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).
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. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.
In late 2019, the WHO assigned 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.
Progressively stronger mitigation efforts to reduce the number of active cases at any given time—"flattening the curve"—allows healthcare services to better manage the same volume of patients. 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.
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.
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. The U.S. Centers for Disease Control and Prevention (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. Proper hand hygiene after any cough or sneeze is encouraged. The CDC has recommended cloth face coverings in public settings where other social distancing measures are difficult to maintain, in part to limit transmission by asymptomatic individuals. 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 the setting of a clinical trial.
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. Distancing guidelines also include that people stay at least 6 feet (1.8 m) apart. There is no medication known to be effective at preventing COVID‑19. 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. In a simple model needs on average over time be kept at or below zero to avoid exponential growth.
As a COVID-19 vaccine is not expected until 2021 at the earliest, a key part of managing COVID‑19 is trying to decrease and delay 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. For the European Centre for Disease Prevention and Control (ECDC) face masks "...could be considered especially when visiting busy closed spaces..." but "...only as a complementary measure..." The U.S. CDC recommends masks in public places where 6-foot social distancing is difficult to maintain, primarily in case you yourself are asymptomatic and to prevent unknowingly spreading the infection.
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.
Per the World Health Organization, as of April 2020, there is no specific treatment for COVID‑19. On 1May 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. Researchers continue working on more effective treatments and many vaccine candidates are in development or testing phases.
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.
When available, respirators (instead of face masks) are preferred. N95 respirators are approved for industrial settings but the FDA has authorised the masks for use under an emergency use authorization (EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific biological agent is not guaranteed for off-label uses. 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 or alternatives, but a percentage of cases are. 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. Whether either of these two leads to the same benefit for people who are critically ill is not known. 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.
Mechanical ventilation had been performed in 79% of critically ill people in hospital including 62% who previously received other treatment. Of these 41% died, according to one study in the United States.
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 behind calls to flatten the curve. One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died. In China, approximately 30% of people in hospital with COVID‑19 are eventually admitted to ICU.
There is high mortality in people ventilated with COVID-19, thought to be due to cytokine storm. Blockade of the IL-6 system is recommended by Australasian Society for Immunology and Allergy to be considered early in severe disease, and is included for consideration in a number of national guidelines.
Research into potential treatments started in January 2020, and several antiviral drugs are in clinical trials.Remdesivir appears to be the most promising. 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.
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.
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 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.
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. According to the Israeli government, the measure was taken to enforce quarantine and protect those who may come into contact with infected citizens. The Association for Civil Rights in Israel, however, said the move was "a dangerous precedent and a slippery slope". 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. Russia deployed facial recognition technology to detect quarantine breakers. 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". The German Government conducted a 48-hour weekend hackathon, which had more than 42,000 participants. Three million people in the UK used an app developed by King's College London and Zoe to track people with COVID‑19 symptoms. 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 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."
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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 make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years. 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%.Pregnant women may be at higher risk for severe infection with COVID‑19 based on data from other similar viruses, like Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), but data for COVID‑19 is lacking. In China, children acquired infections mainly through close contact with their parents or other family members who lived in Wuhan or had traveled there.
The 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. 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.
When someone with existing respiratory problems is infected with COVID-19, they might be at greater risk for severe symptoms. COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.
It is unknown (as of April 2020) if past infection provides effective and long-term immunity in people who recover from the disease. Some of the infected have been reported to develop protective antibodies, so acquired immunity is presumed likely, based on the behaviour of other coronaviruses. Cases in which recovery from COVID‑19 was followed by positive tests for coronavirus at a later date have been reported. However, these cases are believed to be lingering infection rather than reinfection, or false positives due to remaining RNA fragments. An investigation by the Korean CDC of 285 individuals who tested positive for SARS-CoV-2 in PCR tests administered days or weeks after recovery from COVID-19 found no evidence that these individuals were contagious at this later time. Some other coronaviruses circulating in people are capable of reinfection after roughly a year.
The virus is thought to be natural and has an animal origin, through spillover infection. 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. 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. Official publications from the WHO reported the earliest onset of symptoms as 8December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020.
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 the 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 Johns Hopkins University statistics, the global death-to-case ratio is 6.2% (364,459/5,919,364) as of 30 May 2020. 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. Many academics have attempted to calculate these numbers for specific populations.
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. 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.
Total confirmed cases over time
Total deaths over time
Total confirmed cases of COVID‑19 per million people
Total confirmed deaths due to COVID‑19 per million people
Infection fatality rate
Our World in Data states that, as of 25 March 2020, the infection fatality rate (IFR) cannot be accurately calculated. In February, one research group estimated the IFR at 0.94%, with a confidence interval between 0.37 percent to 2.9 percent. The University of OxfordCentre for Evidence-Based Medicine (CEBM) estimated a global CFR of 0.8 to 9.6 percent (last revised 30 April) and IFR of 0.10 to 0.41 percent (last revised 2May). 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.[unreliable medical source?] Firm lower limits of infection fatality rates have been established in a number of locations. As of 7May, in New York City, with a population of 8.4million, 14,162 have died from COVID-19 (0.17% of the population). In Bergamo province, 0.57% of the population has died.[unreliable medical source?] To get a better view on the number of people infected, initial antibody testing has been carried out, but there are no valid scientific reports based on any of them as of yet. On 1May antibody testing in New York suggested an IFR of 0.86%.
The impact of the pandemic and its mortality rate are different for men and women. Mortality is higher in men in studies conducted in China and Italy. The higher risk for men appears in their 50s, and begins to taper off only at 90. In China, the death rate was 2.8 percent for men and 1.7 percent for women. The exact reasons for this sex-difference are not known, but genetic and behavioural factors could be a reason. 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. In Europe, of those infected with COVID‑19, 57% were men; of those infected with COVID‑19 who also died, 72% were men. As of April 2020, the U.S. government is not tracking sex-related data of COVID‑19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza, and SARS affect men and women differently. A higher percentage of health workers, particularly nurses, are women, and they have a higher chance of being exposed to the virus. School closures, lockdowns, and reduced access to healthcare following the COVID-19 pandemic may differentially affect the genders and possibly exaggerate existing gender disparity.
In the U.S., a greater proportion of deaths due to COVID-19 have occurred among African Americans. Structural factors that prevent African Americans from practicing social distancing include their concentration in crowded substandard housing and in "essential" occupations such as public transit and health care. 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. Similar issues affect Native American and Latino communities. According to a U.S health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities.
In January 2020, the World Health Organisation recommended 2019-nCov and 2019-nCoV acute respiratory disease 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.
The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. 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). The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications. Both the disease and virus are commonly referred to as "coronavirus" in the media and public discourse.
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 29 March.
A preliminary study in the U.S. found 38% under-utilization of cardiac care units as compared to normal. 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." There is also concern that persons with symptoms of stroke and appendicitis are delaying seeking help.
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.Tigers and lions 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.Minks at two farms in the Netherlands also tested positive for COVID-19.
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.
No medication or vaccine is approved to treat the disease. International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers. 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. The World Health Organization suspended hydroxychloroquine from its global drug trials for COVID-19 treatments on 26 May 2020 due to safety concerns. It had previously enrolled 3,500 patients from 17 countries in the Solidarity Trial. France, Italy and Belgium also banned the use of hydroxychloroquine as a COVID-19 treatment.
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 harm from misinformation, medical professionals and the public are advised to expect rapid changes to available information, and to be attentive to retractions and other updates.
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. 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.
On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle, Washington, United States. The vaccine contains a harmless genetic code copied from the virus that causes the disease.
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.
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.
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. and one study showing an increase in morbidity along with side effects. 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.
Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID‑19 treatment.
A cytokine storm can be a complication in the later stages of severe COVID‑19. There is preliminary evidence that hydroxychloroquine may be useful in controlling cytokine storms in late-phase severe forms of the disease.
Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed. It is undergoing a phase2 non-randomised trial at the national level in Italy after showing positive results in people with severe disease. Combined with a serum ferritin blood test to identify a cytokine storm (also called cytokine storm syndrome, not to be confused with cytokine release syndrome), it is meant to counter such developments, which are thought to be the cause of death in some affected people. The interleukin-6receptor antagonist was approved by the FDA to undergo a phase III clinical trial assessing the its effectiveness 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. 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 effect on the incidence of CRS.
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.
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