COVID-19

This article is about the disease. For the virus, see Severe acute respiratory syndrome coronavirus 2. For the pandemic, see 2019–20 coronavirus pandemic.

Coronavirus disease 2019 (COVID-19)
Other names	2019-nCoV acute respiratory disease Novel coronavirus pneumonia Wuhan pneumonia Wuhan coronavirus "Coronavirus" or other names for SARS-CoV-2
Symptoms of COVID-19
Pronunciation	/kəˈroʊnəˌvaɪrəs dɪˈziːz, ˈkoʊvɪd/
Specialty	Acute respiratory infection
Symptoms	Fever, cough, shortness of breath
Complications	Pneumonia, acute respiratory distress syndrome, kidney failure
Causes	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Risk factors	Travel, exposure to the virus
Diagnostic method	rRT-PCR testing, immunoassay, CT scan
Prevention	frequent hand washing, cough etiquette, quarantine of infected people and at-risk populations, physical distancing
Treatment	Symptomatic and supportive
Frequency	676,609,955 confirmed cases
Deaths	6,881,955 (2.3% globally, various depending on region. Lower when unconfirmed cases are included)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified in 2019 in Wuhan, the capital of Hubei, China, and has since spread globally, resulting in the 2019–20 coronavirus pandemic. Common symptoms include fever, cough, and shortness of breath. Muscle pain, sputum production, diarrhea, and sore throat are less common. While the majority of cases result in mild symptoms, some progress to pneumonia and multi-organ failure. As of 25 March 2020, the rate of deaths per number of diagnosed cases is 4.5 percent; however, it ranges from 0.2 percent to 15 percent, according to age group and other health problems. The fatality rate varies widely from place to place and over time due to variation in how broadly a population is tested, and due to variations in availability of sufficient healthcare facilities and personnel.

The virus is typically spread during close contact and via respiratory droplets produced when people cough or sneeze. Respiratory droplets may be produced during breathing but it is not considered airborne. It may also spread when one touches a contaminated surface and then their face. It is most contagious when people are symptomatic, although spread may be possible before symptoms appear. The virus can live on surfaces up to 72 hours. Time from exposure to onset of symptoms is generally between two and fourteen days, with an average of five days. The standard method of diagnosis is by reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab. The infection can also be diagnosed from a combination of symptoms, risk factors and a chest CT scan showing features of pneumonia.

Recommended measures to prevent infection include frequent hand washing, social distancing (maintaining physical distance from others, especially from those with symptoms), and keeping unwashed hands away from the face. The use of masks is recommended by some national health authorities for those who suspect they have the virus and their caregivers, but not for the general public, although simple cloth masks may be used by those who desire them. There is no vaccine or specific antiviral treatment for COVID-19. Management involves treatment of symptoms, supportive care, isolation, and experimental measures.

The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 and a pandemic on 11 March 2020. Evidence of local transmission of the disease has been found in many countries across all six WHO regions.

Signs and symptoms

Symptom	%
Fever	87.9
Dry cough	67.7
Fatigue	38.1
Sputum production	33.4
Loss of smell	30 to 66
Shortness of breath	18.6
Muscle or joint pain	14.8
Sore throat	13.9
Headache	13.6
Chills	11.4
Nausea or vomiting	5.0
Nasal congestion	4.8
Diarrhea	3.7 to 31
Haemoptysis	0.9
Conjunctival congestion	0.8

Although those infected with the virus may be asymptomatic, many develop flu-like symptoms, including fever, cough, and shortness of breath. Emergency symptoms include difficulty breathing, persistent chest pain or pressure, confusion, difficulty waking, and bluish face or lips; immediate medical attention is advised if these symptoms are present. Less commonly, upper respiratory symptoms, such as sneezing, runny nose, or sore throat may be seen. Symptoms such as nausea, vomiting, and diarrhea have been observed in varying percentages from 3% to 31% of cases depending on the study. Some cases in China initially presented only with chest tightness and palpitations. In some, the disease may progress to pneumonia, multi-organ failure, and death.

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. 97.5% of people who develop symptoms will do so within 11.5 days of infection.

Cause

Main article: Severe acute respiratory syndrome coronavirus 2

The disease is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously referred to as the 2019 novel coronavirus (2019-nCoV). It is primarily spread between people via respiratory droplets from coughs and sneezes. A study investigating the rate of decay of the virus found no viable viruses after 4 h on copper, 24 h on cardboard, 72 h on stainless steel, and 72 h on plastic. However, detection rates did not reach 100% and varied between surface type (limit of detection was 3.33×10^0.5 TCID₅₀ per liter of air for aerosols, 10^0.5 TCID₅₀ per milliliter of medium for plastic, steel, and cardboard, and 10^1.5 TCID₅₀ per milliliter of medium for copper). Estimation of the rate of decay with a Bayesian regression model suggests that viruses may remain viable up to 18 h on copper, 55 h on cardboard, 90 h on stainless steel, and over 100 h on plastic. The virus remained viable in aerosols throughout the time of the experiment (3 h). The virus has also been found in faeces, and transmission through faeces is being researched.

The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme ACE2, which is most abundant in the type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested that decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and that these hypotheses need to be tested. As the alveolar disease progresses, respiratory failure might develop and death may follow.

The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine. The virus has been found in the faeces of as many as 53% of hospitalised people and more anal swab positives have been found than oral swab positives in the later stages of infection. The virus was found in faeces from 1 to 12 days and 17% of patients continued to present the virus in faeces after no longer presenting them in respiratory samples, indicating that the viral gastrointestinal infection and the potential fecal-oral transmission can last even after viral clearance in the respiratory tract. Reoccurrence of the virus has also been detected through anal swabs suggesting a shift from more oral positive during the early stages of the disease to more anal positive during later periods.

The virus is thought to be natural and have an animal origin, through spillover infection. The origin is unknown but by December 2019 the spread of infection was almost entirely driven by human-to-human transmission. The earliest known infection occurred on 17 November 2019 in Wuhan, China.

• 
  Microscopy image showing SARS-CoV-2. The spikes on the outer edge of the virus particles resemble a crown, giving the disease its characteristic name.
• 
  Schematic diagram of the coronavirus particle. S, spike protein; M, membrane protein; E, envelope protein; N, nucleocapsid protein; structural proteins of coronavirus. Coronavirus virion structure.

Diagnosis

Main article: COVID-19 testing

CDC rRT-PCR test kit for COVID-19

The WHO has published several testing protocols for the disease. The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test can be done on respiratory samples obtained by various methods, including a nasopharyngeal swab or sputum sample. Results are generally available within a few hours to two days. Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value. Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so that laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus. As of 19 March 2020, there were no antibody tests though efforts to develop them are ongoing. The FDA approved the first point-of-care test on 21 March 2020 for use at the end of that month.

Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.

One study in China found that CT scans showed ground-glass opacities in 56%, but 18% had no radiological findings. Bilateral and peripheral ground glass opacities are the most typical CT findings, though they are non-specific. Consolidation, linear opacities and reverse halo sign are other radiological findings. Initially, the lesions are confined to one lung, but as the disease progresses, indications manifest in both lungs in 88% of so-called "late patients" in the study group (the subset for whom time between onset of symptoms and chest CT was 6–12 days). Ground glass opacities are also a common feature in children's disease.

• 
  Typical CT imaging findings
• 
  CT imaging of rapid progression stage

Prevention

See also: 2019–20 coronavirus pandemic § Prevention

An illustration of the effect of spreading out infections over a long period of time, known as flattening the curve; decreasing peaks allows healthcare services to better manage the same volume of patients.

This shows more effective measures can stop the spread, but cases can also increase again if intervention measures are relaxed too early.

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.

Handwashing instructions

Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places, washing hands with soap and warm water often and for at least 20 seconds, practicing good respiratory hygiene and avoiding touching the eyes, nose, or mouth with unwashed hands. The CDC recommends covering the mouth and nose with a tissue when coughing or sneezing, or using inside of the elbow if no tissue is available. They also recommend proper hand hygiene after any cough or sneeze. Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel, and canceling mass gatherings. Social distancing also includes that people stay at least 6 feet apart (about 1.80 meters).

Because a vaccine against SARS-CoV-2 is not expected to become available until 2021 at the earliest, a key part of managing the COVID-19 pandemic is trying to decrease the epidemic peak, known as flattening the epidemic curve through various measures seeking to reduce the rate of new infections. Slowing the infection rate helps decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until therapeutics or a vaccine become available.

According to the WHO, the use of masks is recommended only if a person is coughing or sneezing or when one is taking care of someone with a suspected infection. Some countries also recommend healthy individuals to wear face masks, particularly China, Hong Kong and Thailand. In order to meet the need for masks, the WHO estimates that global production will need to increase by 40%. Hoarding and speculation have worsened the problem, with the price of masks increasing sixfold, N95 respirators tripled, and gowns doubled. Some health experts consider wearing non-medical-grade masks and other face coverings like scarves or bandanas a good way to prevent people from touching their mouths and noses, even if non-medical coverings would not protect against a direct sneeze or cough from an infected person.

Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask 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. The CDC also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose, coughing, or sneezing. It further recommends using an alcohol-based hand sanitizer with at least 60% alcohol, but only when soap and water are not readily available.

For areas where commercial hand sanitizers are not readily available, the WHO suggested two formulations for the local production. In both these formulations the antimicrobial activity of ethanol or isopropanol is enhanced by a low concentration of hydrogen peroxide while glycerol acts as a humectant.

Management

Four steps to putting on personal protective equipment

People are managed with supportive care, which may include fluid, oxygen support, and supporting other affected vital organs. Steroids such as methylprednisolone are not recommended unless the disease is complicated by acute respiratory distress syndrome.

The CDC recommends that those who suspect they carry the virus wear a simple face mask. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration. While the WHO does not oppose the use of non-steroidal anti-inflammatory drugs such as ibuprofen for symptoms, some recommend paracetamol (acetaminophen) for first-line use. There are four reported cases of children who developed severe symptoms after taking ibuprofen. 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.

The WHO and Chinese National Health Commission have published recommendations for taking care of people who are hospitalised with COVID-19. Intensivists and pulmonologists in the US have compiled treatment recommendations from various agencies into a free resource, the IBCC.

Personal protective equipment

Precautions must be taken to minimize the risk of virus transmission, especially in healthcare settings when performing procedures that can generate aerosols, such as intubation or hand ventilation. Some public health officials have complained that the limited supply of protective gear should not be used to expand outpatient testing. New York City has departed from CDC guidelines and is recommending that testing be limited to hospitalized patients to conserve supplies.

CDC outlines the specific guidelines for the use of personal protective equipment (PPE) during the pandemic. The recommended gear is as follows:

1. gown
2. mask or respirator,
3. goggles or a face shield,
4. medical gloves

The N95 respirators are approved for industrial settings but the FDA has authorized the masks for use under an Emergency Use Authorization (EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific biological agent is not guaranteed for off-label uses. When masks are not available the CDC recommends using face shields, or as a last resort homemade masks.

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. Some Canadian doctors recommend the use of invasive mechanical ventilation because this technique limits the spread of aerosolized transmission vectors. Severe cases are most common in older adults (those older than 60 years and especially those older than 80 years). Many developed countries do not have enough hospital beds per capita, which limits a health system's capacity to handle a sudden spike in the number of COVID-19 cases severe enough to require hospitalization. This limited capacity is a significant driver of the need to flatten the curve (to keep the speed at which new cases occur and thus the number of people sick at one point in time lower). One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died. Every ventilator is worth its weight in gold as a source says a third of all Coronavirus patients could need it.</ref>https://meduza.io/amp/en/feature/2020/03/21/the-ventilator-problem

Experimental treatment

See also: Research

No medications are approved to treat the disease by the WHO although some are recommended by individual national medical authorities. Research into potential treatments started in January 2020, and several antiviral drugs are in clinical trials. Although new medications may take until 2021 to develop, several of the medications being tested are already approved for other uses, or are already in advanced testing. Antiviral medication may be tried in people with severe disease. The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.

Information technology

See also: Algorithmic regulation

In February 2020, China launched a mobile app to deal with the disease outbreak. Users are asked to enter their name and ID number. The app is able to detect 'close contact' using surveillance data and therefore a potential risk of infection. Every user can also check the status of three other users. If a potential risk is detected, the app not only recommends self-quarantine, it also alerts local health officials.

Big data analytics on cellphone data, facial recognition technology, mobile phone tracking and artificial intelligence are used to track infected people and people whom they contacted in South Korea, Taiwan and Singapore. In March 2020, the Israeli government enabled security agencies to track mobile phone data of people supposed to have coronavirus. The measure was taken to enforce quarantine and protect those who may come into contact with infected citizens. Also in March 2020, Deutsche Telekom shared private cellphone data with the German federal government agency, Robert Koch Institute, in order to research and prevent the spread of the virus. Russia deployed facial recognition technology to detect quarantine breakers. Italian regional health commissioner Giulio Gallera said that he has been informed by mobile phone operators that "40% of people are continuing to move around anyway". German government conducted a 48 hours weekend hackathon with more than 42.000 participants. Also the president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of coronavirus.

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.

Prognosis

The severity of diagnosed COVID19 cases in China

Case fatality rates by age group in China. Data through 11 February 2020.

Case fatality rate in China depending on other health problems. Data through 11 February 2020.

The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. Mild cases typically recover within two weeks, while those with severe or critical disease may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks.

Children of all ages are susceptible to the disease, but are likely to have milder symptoms and a much lower chance of severe disease than adults; in those younger than 50 years, the risk of death is less than 0.5%, while in those older than 70 it is more than 8%. Pregnant women are at particular risk for severe infection.

In some people, COVID-19 may affect the lungs causing pneumonia. In those most severely affected, COVID-19 may rapidly progress to acute respiratory distress syndrome (ARDS) causing respiratory failure, septic shock, or multi-organ failure. Complications associated with COVID-19 include sepsis, abnormal clotting, and damage to the heart, kidneys, and liver. Clotting abnormalities, specifically an increase in prothrombin time, have been described in 6% of those admitted to hospital with COVID-19, while abnormal kidney function is seen in 4% of this group. Liver injury as shown by blood markers of liver damage is frequently seen in severe cases.

Some studies have found that the neutrophil to lymphocyte ratio (NLR) may be helpful in early screening for severe illness.

Many of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. The Istituto Superiore di Sanità reported that 68.9% of deaths from the disease in the country had at least one preexisting condition, with patients that had preexisting conditions having an average of 2.7 conditions. According to the same report, the median time between onset of symptoms and death was eight days, with half that time being spent hospitalized. However, patients transferred to an ICU had a median time of five days between hospitalization and death. In a study of early cases, the median time from exhibiting initial symptoms to death was 14 days, with a full range of six to 41 days. In a study by the National Health Commission (NHC) of China, men had a death rate of 2.8% while women had a death rate of 1.7%. Histopathological examinations of post-mortem lung samples show diffuse alveolar damage with cellular fibromyxoid exudates in both lungs. Viral cytopathic changes were observed in the pneumocytes. The lung picture resembled acute respiratory distress syndrome (ARDS). In 11.8% of the deaths reported by the National Health Commission of China, heart damage was noted by elevated levels of troponin or cardiac arrest.

Availability of medical resources and the socioeconomics of a region may also affect mortality. Estimates of the mortality from the condition vary because of those regional differences, but also because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be overestimated. However, the fact that deaths are the result of cases contracted in the past can mean the current mortality rate is underestimated.

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

Concerns have been raised about long-term sequelae of the disease. The Hong Kong Hospital Authority found a drop of 20% to 30% in lung capacity in some people who recovered from the disease, and lung scans suggested organ damage.

Case fatality rates (%) by age and country
Age	0–9	10–19	20–29	30–39	40–49	50–59	60–69	70–79	80+
China as of 11 February	0.0	0.2	0.2	0.2	0.4	1.3	3.6	8.0	14.8
Italy as of 19 March	0.0	0.0	0.0	0.4	0.6	1.2	4.9	15.3	23.6
South Korea as of 23 March	0.0	0.0	0.0	0.1	0.1	0.4	1.6	6.3	11.6
Spain as of 22 March	0.0	0.5	0.3	0.1	0.3	0.6	2.2	5.2	17.9

Case fatality rates (%) by age in the United States
Age	0-19	20-44	45-54	55-64	65-74	75-84	≥85
United States as of 16 March	0.0	0.1-0.2	0.5-0.8	1.4-2.6	2.7-4.9	4.3-10.5	10.4-27.3
Note: The lower bound includes all cases. The upper bound excludes cases that were missing data.

Epidemiology

Main article: 2019–20 coronavirus pandemic

The case fatality rate (CFR) depends on the availability of healthcare, the typical age and health problems within the population, and the number of undiagnosed cases. Preliminary research has yielded case fatality rate numbers between 2% and 3%; in January 2020 the WHO suggested that the case fatality rate was approximately 3%, and 2% in February 2020 in Hubei. Other CFR numbers, which adjust for differences in time of confirmation, death or remission but are not peer reviewed, are respectively 7% and 33% for people in Wuhan 31 January. An unreviewed preprint of 55 deaths noted that early estimates of mortality may be too high as asymptomatic infections are missed. They estimated a mean infection fatality ratio (IFR, the mortality among infected) ranging from 0.8% to 0.9%. A peer-reviewed article published on 19 March estimated the overall symptomatic case fatality risk as 1.4% (IQR 0.9–2.1%). The outbreak in 2019–2020 has caused at least 676,609,955Template:Edit sup confirmed infections and 6,881,955Template:Edit sup deaths.

The epidemic spreads faster where people are close together and/or travel to other areas. Researchers found that travel restrictions can reduce the basic reproduction number from 2.35 to 1.05, allowing the epidemic to be manageable.

An observational study of nine people found no vertical transmission from mother to the newborn. Also, a descriptive study in Wuhan found no evidence of viral transmission through vaginal sex (from female to partner), but authors note that transmission during sex might occur through other routes.

• 
  Total confirmed cases over time
• 
  Total deaths over time
• 
  Total confirmed cases of COVID-19 per million people, 20 March 2020
• 
  Total confirmed deaths due to COVID-19 per million people, 24 March 2020

Terminology

The World Health Organization announced in February 2020 that COVID-19 is the official name of the disease. World Health Organization chief Tedros Adhanom Ghebreyesus explained that CO stands for corona, VI for virus and D for disease, while 19 is for the year that the outbreak was first identified; 30 December 2019. The name had been chosen to avoid references to a specific geographical location (i.e. China), animal species, or group of people, in line with international recommendations for naming aimed at preventing stigmatisation.

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

Coronaviruses were named in 1968 for their appearance in electron micrographs which was reminiscent of the solar corona, corona meaning crown in Latin.

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.

Vaccine

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. There are three vaccination strategies being investigated. First, researchers aim to build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune response of the human body to a new infection with COVID-19. A second strategy, subunit vaccines, aims to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor. A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and efficacy.

On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle. The vaccine contains a harmless genetic code copied from the virus that causes the disease.

One difficulty with vaccine development is that older people, who are more vulnerable to the disease, are often poorly vaccinated due to age-related degradation of the thymus. Therefore, alternative methods will need to be developed to increase immunity in this population. One method being considered is treatment with recombinant interleukin 7, which plays an extremely important role in the maturation and reproduction of lymphoid cells. Using interleukin 7 along with vaccines can boost the immune system's response to infections and increase the growth of restoration cells, thus lowering the risk of death in older people.

Antivirals

Main article: COVID-19 drug repurposing research

Several existing antiviral medications are being looked at to treat COVID-19 and some are moving into clinical trials. In March 2020, WHO has launched a multi-country trial involving 10 countries called "Solidarity" in response to COVID-19 pandemic. Remdesivir, chloroquine and hydroxychloroquine, ritonavir/lopinavir and ritonavir/lopinavir combined with interferon beta are the experimental treatments currently being researched under Solidarity Trial.

There is tentative evidence for remdesivir as of March 2020. Remdesivir inhibits SARS-CoV-2 in vitro. Phase 3 clinical trials are being conducted in the US, in China, and in Italy.

Chloroquine, previously used to treat malaria, was being studied in China in February 2020, with positive preliminary results. Chloroquine and hydroxychloroquine effectively inhibit SARS-CoV-2 in vitro, with hydroxychloroquine proving to be more potent than chloroquine and with a more tolerable safety profile. Preliminary results from a trial suggested that chloroquine is effective and safe in treating COVID-19 associated pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course". However, there are calls for more review of the research to date. The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of person's hospital stay" and recommended it for people diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.

On 17 March, the Italian Pharmaceutical Agency included chloroquine and hydroxychloroquine in the list of drugs with positive preliminary results for treatment of COVID-19. Korean and Chinese Health Authorities recommend the use of chloroquine. However, the Wuhan Institute of Virology, while recommending a daily dose of one gram, notes that twice that dose is highly dangerous and could be lethal. As of 20 March 2020 the treatment has not yet been approved by the U.S. Food and Drug Administration.

The Chinese 7th edition guidelines also include interferon, ribavirin, or umifenovir for use against COVID-19.

In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness. Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.

Studies have demonstrated that initial spike protein priming by transmembrane protease serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2 via interaction with the ACE2 receptor. These findings suggest that the TMPRSS2 inhibitor camostat approved for use in Japan for inhibiting fibrosis in liver and kidney disease might constitute an effective off-label treatment.

In February 2020, Favipiravir was being studied in China for experimental treatment of the emergent COVID-19 disease.

Anti-cytokine storm

Cytokine storm, a life-threatening medical condition, can be a complication in the later stages of severe COVID-19. There is evidence that hydroxychloroquine has anti-cytokine storm properties.

Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed. It is undergoing a phase 2 non randomized test at the national level in Italy after showing positive results in people with severe disease. 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. 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.

The Feinstein Institute of Northwell Health announced in March a study on "a human antibody that may prevent the activity" of IL-6.

Enhanced innate immunity

The eicosanoid signaling molecule leukotriene B4 (LTB4) is a possible (as yet untested) candidate drug for treatment of COVID-19. In the lungs, LTB4 is produced in alveolar macrophages, and it recruits neutrophil white blood cells.

A 1989 study in humans reported an approximately 17-fold (1700%) increase in neutrophil white blood cells in recovered human lung fluid 4 hours after LTB4 injection into the human lung (10 ml LTB4 diluted to 5 x 10-7 M in sterile saline). Notably, there was no significant change in lung epithelial permeability associated with LTB4-induced neutrophil recruitment. Therefore, it was suggested that LTB4 can recruit neutrophils without initiating an inflammatory cascade within the lungs.

Several subsequent studies have reported that LTB4 exerts potent anti-viral (and general anti-microbial) effects in the lung. For example, a 2008 study in mice reported that daily i.v. treatment with LTB4 led to a significant decrease in lung viral loads of influenza A at day 5 post-infection. A follow-up study in 2009 reported that LTB4 potentiates cytokine signaling by human white blood cells (neutrophils in particular), and that this action is not sensitive to chloroquine (raising the possibility that chloroquine and LTB4 could be used in combination to combat viral infection).

More recently, a 2019 study in mice reported that a single dose of LTB4 as late as five days post-infection with influenza A virus (at peak viral load) reduces proliferation of inflammatory monocyte-derived macrophages, controls tissue damage and enhanced significant survival against lethal influenza A infection. With regard to the mechanism of LTB4 action, it was found that LTB4 promotes production of interferon-α (IFN-α) (involved in innate immunity in viral infection) by pulmonary interstitial macrophages, resulting in inhibition of inflammatory monocyte-derived macrophages (the excessive accumulation of which is associated with ‘cytokine storm’ and mortality). However, in influenza A infected mice, LTB4 did not significantly alter neutrophil number.

Furthermore, a 2011 study in humans reported that nasal fluids recovered from healthy subjects who received nasally-administered LTB4, efficiently killed human coronavirus, respiratory syncytial virus, and influenza B virus.

Passive antibody therapy

Transfering donated blood containing antibodies produced by the immune systems of those who have recovered from COVID-19 to people who need them is being investigated as a nonvaccine method of immunization. This strategy was tried for SARS. Viral neutralization is the anticipated mechanism of action by which passive antibody therapy can mediate defense against SARS-CoV-2. Other mechanisms, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may however be possible. Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development. 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.

See also

• Coronavirus diseases, a group of closely related syndromes
• Li Wenliang, a doctor at Central Hospital of Wuhan, who later contracted COVID-19 and died of it after raising awareness of the spread of the virus.
• Disease X, a World Health Organisation term

Further reading

• Guo YR, Cao QD, Hong ZS, et al. (March 2020). "The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—an update on the status". Mil Med Res. 7 (1): 11. doi:10.1186/s40779-020-00240-0. PMC 7068984. PMID 32169119.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

• Coronavirus disease (COVID-19) outbreak by the World Health Organization
• Coronavirus 2019 (COVID-19) by the U.S. Centers for Disease Control and Prevention
• Coronavirus Disease 2019 (COVID-19) by The Journal of the American Medical Association
• Coronavirus: Latest news and resources by the BMJ Publishing Group
• Novel Coronavirus Information Center by Elsevier
• COVID-19 Resource Centre by The Lancet
• SARS-CoV-2 and COVID-19 by Nature
• Coronavirus (Covid-19) by New England Journal of Medicine
• Covid-19: Novel Coronavirus by Wiley Publishing
• "SARS-CoV-2 related protein structures". Protein Data Bank.