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Covid19 from wikipedia

Terminology

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.[30][31]

While the disease is named COVID-19, the virus that causes it was named SARS-CoV-2.[32] The virus was initially referred to as the 2019 novel coronavirus or 2019-nCoV.[33] The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.[32]

Signs and symptoms

Rate of symptoms[34]SymptomPercentageFever87.9%Dry cough67.7%Fatigue38.1%Sputum production33.4%Shortness of breath18.6%Muscle pain or joint pain14.8%Sore throat13.9%Headache13.6%Chills11.4%Nausea or vomiting5.0%Nasal congestion4.8%Diarrhoea3.7%Haemoptysis0.9%Conjunctival congestion0.8%

Although those infected with the virus may be asymptomatic, many develop flu-like symptoms including fever, cough, and shortness of breath.[6][35][36] Less commonly, upper respiratory symptoms such as sneezing, runny nose, or sore throat may be seen. Gastorintestinal symptoms such as nausea, vomiting, and diarrhoea are seen in a minority of cases.[37] In some, the disease may progress to pneumonia, multi-organ failure, and death.[10][14]

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 14 days.[38][39]

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.[40]

Course and complications

The severity of COVID-19 varies. The disease may take a mild course with little or no symptoms, resembling other common upper respiratory diseases such as the common cold. However, in some 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.[41][42]

Complications associated with COVID-19 include sepsis, abnormal clotting, and damage to the heart, kidneys, and liver. Clotting abnormalities, specifically an increase in the time required for the blood to clot (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.[43] Blood markers of damage to the heart (Troponin I) are increased in more than 50% of severe cases of COVID-19, and abnormal heart rhythms leading to cardiac arrest have been described.[44] Liver injury as shown by blood markers of liver damage is frequently seen in severe cases, although liver failure has not been described as of March 2020.[45]

Several factors predict the severity of COVID-19 infection. Children are likely to have milder symptoms and a much lower chance of severe disease than adults.[46] Older age and a high SOFA score (a clinical scoring scale assessing function of various metabolic systems and organs, e.g. lungs, heart, liver, kidneys, etc.) are associated with a worse prognosis. Those with pre-existing heart conditions are at greater risk of cardiac complications. Blood tests associated with more severe disease include d-dimer greater than 1 μg/mL on admission; elevated levels of blood interleukin-6, high-sensitivity cardiac troponin I, lactate dehydrogenase; and abnormally low levels of lymphocytes (a type of white blood cell).

Cause

  1. Main article: Severe acute respiratory syndrome coronavirus 2

  2. 📷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.

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).[47] It is primarily spread between people via respiratory droplets from coughs and sneezes.[18] The virus has been found in the feces of infected persons, but whether transmission through feces is possible is unknown.[48]

SARS-CoV-2 is trasmitted from person to person. It can survive within aerosols, generated by humans while breathing or coughing for 3 hours. It can stay stable on hard surfaces as well. On plastic and stainless steel SARS-CoV-2 can last up to 3 days.[49]

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.[50] 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,[51][52] though another view is that increasing ACE2 using Angiotensin II receptor blocker medications could be protective and that these hypotheses need to be tested.[53] As the alveolar disease progresses, respiratory failure might develop and death may follow.[52] ACE2 might also be the path for the virus to assault the heart causing acute cardiac injury. People with existing cardiovascular conditions have the worst prognosis.[44]

The virus is thought to have an animal origin,[54] through spillover infection.[55] 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.[56][57] On 14 March 2020, South China Morning Post reported that a 55-year-old from Hubei province could have been the first person to have contracted the disease on 17 November 2019.[58] 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%.[58]

Diagnosis

  1. Main article: COVID-19 testing

  2. 📷CDC rRT-PCR test kit for COVID-19[59]

The WHO has published several testing protocols for the disease.[60] The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR).[61] The test can be done on respiratory samples obtained by various methods, including a nasopharyngeal swab or sputum sample.[62] Results are generally available within a few hours to two days.[63][64] Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value.[65] 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.[10][66][67]

As of 26 February 2020, there were no antibody tests or point-of-care tests though efforts to develop them are ongoing.[68]

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.[21] 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 more sensitivity (98%) than the polymerase chain reaction (71%).[22] 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.[69]

One study in China found that CT scans showed ground-glass opacities in 56%, but 18% had no radiological findings.[70] Bilateral and peripheral ground glass opacities are the most typical CT findings.[71] Consolidation, linear opacities and reverse halo sign are other radiological findings.[71] 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).[71]

  1. 📷 Typical CT imaging findings

  2. 📷 CT imaging of rapid progression stage

Prevention

  1. See also: 2019–20 coronavirus pandemic § Prevention

  2. 📷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 people, and allows for more preparation time.[72][73][74]

  3. 📷Alternatives to flattening the curve[75][76]

Because a vaccine against SARS-CoV-2 is not expected to become available until 2021 at the earliest,[77] 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.[73] 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.[73]

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 hot water often, practice good respiratory hygiene and avoid touching the eyes, nose, or mouth with unwashed hands.[78][79] Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel, and canceling mass gatherings.[80]

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.[81]

To prevent transmission of the virus, the Centers for Disease Control and Prevention (CDC) in the United States 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.[82][83] 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.[78] The WHO advises individuals to avoid touching the eyes, nose, or mouth with unwashed hands.[79] Spitting in public places also should be avoided.[84]

Management

  1. 📷Four steps to putting on personal protective equipment[85]

There are no specific antiviral medications. People are managed with supportive care such as fluid and oxygen support if needed,[86][87] while at the same time, there is monitoring and supporting other affected vital organs.[88] The WHO and Chinese National Health Commission have published treatment recommendations for taking care of people who are hospitalised with COVID-19.[89][90] Steroids such as methylprednisolone are not recommended unless the disease is complicated by acute respiratory distress syndrome.[91][92] Intensivists and pulmonologists in the US have compiled treatment recommendations from various agencies into a free resource, the IBCC.[93][94] CDC recommends that those who suspect they carry the virus wear a simple face mask.[24]

Ibuprofen, an anti-inflammatory drug commonly used to reduce fever, has been used to treat flu-like symptoms brought about by COVID-19.[95] Ibuprofen increases ACE2 enzymes at cell level which could worsen COVID-19 infections,[96] raising concerns on its usage. The WHO as well as an article published at The BMJ warn against the use of ibuprofen, recommending using paracetamol instead.[97][98][better source needed]

The use of extracorporeal membrane oxygenation (ECMO) has been utilized to address the issue of respiratory failure, but its benefits are still under consideration.[70][99]

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.[100]

CDC outlines the specific personal protective equipment and the order in which healthcare providers should put it on when dealing with someone who may have COVID-19: 1) gown, 2) mask or respirator,[101][102] 3) goggles or a face shield, 4) gloves.[103][104]

Mechanical ventilation

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). This component of treatment is the biggest rate-limiter of health system capacity that drives 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).[citation needed]

One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died.[70]

Experimental treatment

Antiviral medication may be tried in people with severe disease.[86] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[105] There is tentative evidence for remdesivir as of March 2020.[106] Lopinavir/ritonavir is also being studied in China.[107] Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.[108]

Chloroquine and hydroxychloroquine

Chloroquine, normally used to treat malaria, was being trialled in China in February 2020, with preliminary results that seem positive.[109][110] Chloroquine phosphate has a wide range of antiviral effects and had been proposed as a treatment for SARS-CoV-2.[111] In vitro tests have shown that it can inhibit the virus[112] and 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.[113] On March 17 the Italian Pharmaceutical Agency has included chloroquine and hydroxychloroquine in the list of drugs with positive preliminary results for treatment of COVID-19.[114] In vitro studies have demonstrated that hydroxychloroquine is more potent than chloroquine against SARS-CoV-2 with a more tolerable safety profile.[115]

Tocilizumab

Tocilizumab has been included in treatment guidelines by China's National Health Commission after a completed small study by the University of Science and Technology of China.[116][117] The medication is undergoing a phase 2 non randomized test at the national level in Italy after showing positive results in people with severe disease.[118][119][114] 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.[120][121] The interleukin-6 receptor antagonist was approved by the FDA for treatment against cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017.[122]

Information technology

In February 2020, China launched a mobile app to deal with the disease outbreak.[123] 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.[124]

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.[125]

Psychological support

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.[126][127]

Prognosis

Many of those who die of COVID-19 have preexisting conditions, including hypertension, diabetes mellitus, and cardiovascular disease.[128] In a study of early cases, the median time from exhibiting initial symptoms to death was 14 days, with a full range of 6 to 41 days.[129] 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%.[130] 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%.[130] No deaths had occurred in people younger than 10 as of 26 February 2020.[130] Availability of medical resources and the socioeconomics of a region may also affect mortality.[131]

Histopathological examinations of post-mortem lung samples showed 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).[132]

It is unknown if past infection provides effective and long-term immunity in people who recover from the disease.[133] Immunity is likely, based on the behaviour of other coronaviruses,[134] but cases in which recovery from COVID-19 have been followed by positive tests for coronavirus at a later date have been reported.[135][136] It is unclear if these cases are the result of reinfection, relapse, or testing error.

Case fatality rates (%) by age and countryAge80+70–7960–6950–5940–4930–3920–2910–190–9China as of 11 February[56]14.88.03.61.30.40.20.20.20.0Italy as of 16 March[137]19.211.83.21.00.30.20.00.00.0South Korea as of 17 March[138]10.25.41.60.40.10.10.00.00.0

  1. 📷 The severity of diagnosed COVID19 cases in China[139]

  2. 📷 Case fatality rates by age group in China. Data through 11 February 2020.[56]

  3. 📷 Case fatality rate depending on other health problems

  4. 📷 Total deaths

Long-term health

The Hong Kong Hospital Authority found a drop of 20% to 30% in lung capacity in two to three of around a dozen people who recovered from the disease. The people who recovered gasp if they walk more quickly. Lung scans of the nine people infected at Princess Margaret Hospital suggested they had sustained organ damage.[140]

Children

In a study of children in China with laboratory-confirmed or clinically-suspected cases of COVID-19, children of all ages were found to be susceptible and no sex difference in susceptibility was found. Of all children, 4.4% of cases were asymptomatic, 50.9% were mild, 38.8% were moderate, 5.2% were severe, and 0.6% were critical. One fatality, a 14-year-old boy, occurred in the study population.[141]

Severity by age group[141]AsymptomaticMildModerateSevereCriticalTotal<11.8%54.1%33.5%8.7%1.8%379 cases1-5 yrs3.0%49.7%40.0%6.9%0.4%493 cases6-10 years5.8%53.4%36.7%4.2%0.0%521 cases11-15 years6.5%48.2%41.2%3.4%0.7%413 cases>15 years4.5%49.0%43.6%2.7%0.3%335 casesAll4.4%51.0%38.8%5.2%0.6%2141 cases

Epidemiology

  1. Main article: 2019–20 coronavirus pandemic

  2. 📷Total confirmed cases over time

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.[142][143] Preliminary research has yielded case fatality rate numbers between 2% and 3%;[15] in January 2020 the WHO suggested that the case fatality rate was approximately 3%,[144] and 2% in February 2020 in Hubei.[145] Other CFR numbers, which adjust for differences in time of confirmation, death or cured, are respectively 7%[146] and 33% for people in Wuhan 31 January.[147] 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% - 0.9%.[148] The outbreak in 2019–2020 has caused at least 198,004edit[7] confirmed infections and 7,948edit[7] deaths.

An observational study of nine people found no vertical transmission from mother to the newborn.[149] 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.[150]

Research

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.[52]

Vaccine

  1. Main article: COVID-19 vaccine

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.[151] 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.[152]

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.[153]

Antivirals

No medication has yet been approved to treat coronavirus infections in humans by the WHO although some are recommended by the Korean and Chinese medical authorities.[154] Trials of many antivirals have been started in COVID-19 including oseltamivir, lopinavir/ritonavir, ganciclovir, favipiravir, baloxavir marboxil, umifenovir, and interferon alfa but currently there are no data to support their use.[155] Korean Health Authorities recommend lopinavir/ritonavir or chloroquine[156] and the Chinese 7th edition guidelines include interferon, lopinavir/ritonavir, ribavirin, chloroquine, and/or umifenovir.[157]

Research into potential treatments for the disease was started in January 2020, and several antiviral drugs are already in clinical trials.[158][159] Although completely new drugs may take until 2021 to develop,[160] several of the drugs being tested are already approved for other antiviral indications, or are already in advanced testing.[154]

Remdesivir and chloroquine effectively inhibit the coronavirus in vitro.[108] Remdesivir is being trialled in US and in China.[155] Preliminary results from a multicentric trial, announced in a press conference and described by Gao, Tian and Yang, 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".[109] On 16 March 2020, Professor Didier Raoult, announced that a trial involving 24 patients from the south east of France supported the claim that chloroquine was an effective treatment for COVID-19.[161] 600mg of hydroxychloroquine (brand name Plaquenil) was administered to these patients every day for 10 days.

Recent studies have demonstrated that initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2, SARS-CoV and MERS-CoV via interaction with the ACE2 receptor.[162][163] These findings suggest that the TMPRSS2 inhibitor Camostat approved for clinical use in Japan for inhibiting fibrosis in liver and kidney disease, postoperative reflux esophagitis and pancreatitis might constitute an effective off-label treatment option.[162]

Passive antibody therapy

Using blood donations from healthy people who have already recovered from COVID-19 is being investigated,[164] a strategy that has also been tried for SARS, an earlier cousin of COVID-19.[164] The mechanism of action is that the antibodies naturally produced in the immune systems of those who have already recovered are transferred to people in need of them via a nonvaccine form of immunization.[164] Other forms of passive antibody therapy, such as with manufactured monoclonal antibodies, may come later after biopharmaceutical development,[164] but convalescent serum production could be increased for quicker deployment.[165]

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