Covid-19 (Coronavirus) - Simply Elliott

As the world has become consumed by this pandemic, I thought I would capture some of the information here. This is such a crazy time in our history, and I want to be able to pull together not only our masked memories, but the medical and political information as well.

All of the below information has been copied from external sources.

Coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, Hubei, China, and has resulted in an ongoing pandemic. The first confirmed case has been traced back to 17 November 2019 in Hubei. As of 8 July 2020, more than 11.7 million cases have been reported across 188 countries and territories, resulting in more than 543,000 deaths. More than 6.41 million people have recovered.

Common symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. While the majority of cases result in mild symptoms, some progress to acute respiratory distress syndrome (ARDS) possibly precipitated by cytokine storm, multi-organ failure, septic shock, and blood clots. The time from exposure to onset of symptoms is typically around five days, but may range from two to fourteen days.

The virus is primarily spread between people during close contact, [a] most often via small droplets produced by coughing, [b] sneezing, and talking. The droplets usually fall to the ground or onto surfaces rather than travelling through air over long distances, although in some cases they may remain airborne for tens of minutes. Less commonly, people may become infected by touching a contaminated surface and then touching their face. It is most contagious during the first three days after the onset of symptoms, although spread is possible before symptoms appear, and from people who do not show symptoms. The standard method of diagnosis is by real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab. Chest CT imaging may also be helpful for diagnosis in individuals where there is a high suspicion of infection based on symptoms and risk factors; however, guidelines do not recommend using CT imaging for routine screening.

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. The use of cloth face coverings such as a scarf or a bandana has been recommended by health officials in public settings to minimize the risk of transmissions, with some authorities requiring their use. Health officials also stated that medical-grade face masks, such as N95 masks, should only be used by healthcare workers, first responders, and those who directly care for infected individuals.

There are no vaccines nor specific antiviral treatments for COVID-19. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures. The World Health Organization (WHO) declared the COVID‑19 outbreak a public health emergency of international concern (PHEIC) on 30 January 2020 and a pandemic on 11 March 2020. Local transmission of the disease has occurred in most countries across all six WHO regions.

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

Most 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 out of 8.8% of deaths where medical charts were available, 97% of people had at least one comorbidity with the average person having 2.7 diseases. According to the same report, the median time between the onset of symptoms and death was ten days, with five being spent hospitalized. However, people transferred to an ICU had a median time of seven 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%. 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. According to March data from the United States, 89% of those hospitalized had preexisting conditions.

The availability of medical resources and the socioeconomics of a region may also affect mortality. 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. This may also lead to post-intensive care syndrome following recovery.

HISTORY

The virus is thought to be natural and has an animal origin, through spillover infection. The first known human infections were in China. A study of the first 41 cases of confirmed COVID‑19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019. Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020, George Gao, the director of the Chinese Center for Disease Control and Prevention, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but it was not the site of the initial outbreak. Traces of the virus have been found in wastewater that was collected from Milan and Turin, Italy, on 18 December 2019.

There are several theories about where the very first case (the so-called patient zero) originated. According to an unpublicized report from the Chinese government, the first case can be traced back to 17 November 2019; the person was a 55-year old citizen in the Hubei province. There were four men and five women reported to be infected in November, but none of them were “patient zero”. By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of coronavirus cases in Hubei gradually increased, reaching 60 by 20 December and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. That evening, the Wuhan Municipal Health Commission issued a notice to various medical institutions on “the treatment of pneumonia of unknown cause”. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumors, and another, Ai Fen, was reprimanded by her superiors for raising the alarm.

The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases—enough to trigger an investigation.

During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its “pandemic potential”. On 30 January, the WHO declared the coronavirus a public health emergency of international concern. By this time, the outbreak spread by a factor of 100 to 200 times.

On 31 January 2020, Italy had its first confirmed cases, two tourists from China. As of 13 March 2020, the WHO considered Europe the active center of the pandemic. On 19 March 2020, Italy overtook China as the country with the most deaths. By 26 March, the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travelers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019 and a person in the United States who died from the disease on 6 February 2020.

On 11 June 2020, after 55 days without a locally transmitted case, Beijing reported the first COVID-19 case, followed by two more cases on 12 June. By 15 June, 79 cases were officially confirmed. Most of these patients went to Xinfadi Wholesale Market.

EPIDEMIOLOGY

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 4.6% (543,595/11,797,213) as of 8 July 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.

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

INFECTION FATALITY RATE

Infection fatality rate (or infection fatality ratio) is distinguished from case fatality rate. The case fatality rate (“CFR”) for a disease is the proportion of deaths from the disease compared to the total number of people diagnosed with the disease (within a certain period of time). The infection fatality ratio (“IFR”), in contrast, is the proportion of deaths among all the infected individuals. IFR, unlike CFR, attempts to account for all asymptomatic and undiagnosed infections.

Our World in Data states that, as of 25 March 2020, the infection fatality rate (IFR) for coronavirus cannot be accurately calculated. In February, the World Health Organization reported estimates of IFR between 0.33% and 1%. The University of Oxford Centre 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 2 May). According to CEBM, random antibody testing in Germany suggested an IFR of 0.37% (0.12% to 0.87%) there. Firm lower limits of infection fatality rates have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. As of 25 June, in New York City, with a population of 8.4 million, 22,421 individuals (17,753 confirmed and 4,668 probable) have died with COVID-19 (0.27% of the population). In Bergamo province, 0.57% of the population has died. The CDC estimates for planning purposes that the fatality rate among those who are symptomatic is 0.4% (0.2% to 1%) and that 35% of infected individuals are asymptomatic, for an overall infection fatality rate of 0.26% (as of 20 May). To get a better view on the number of people infected, as of April 2020, initial antibody testing had been carried out, but peer-reviewed scientific analyses had not yet been published. On 1 May antibody testing in New York suggested an IFR of 0.86%.

SEX DIFFERENCES

Early reviews of epidemiologic data showed greater impact of the pandemic and a higher mortality rate in men in China and Italy. The Chinese Center for Disease Control and Prevention reported the death rate was 2.8 percent for men and 1.7 percent for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors.

ETHNIC DIFFERENCES

In the US, 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 US 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 the U.K., a greater proportion of deaths due to COVID-19 have occurred in those of a Black, Asian, and other ethnic minority background. Several factors such as poverty, poor nutrition and living in overcrowded properties, may have caused this.

SOCIETY AND CULTURE

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”. In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East Respiratory Syndrome, and Zika virus.

In January 2020, the World Health Organization 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, D for 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.

MISINFORMATION

After the initial outbreak of COVID‑19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.

Decreased emergency room use; In Austria, 39% fewer persons sought help for cardiac symptoms in the month of March. A study estimated that there were 110 incidents of preventable cardiac death as compared to 86 confirmed deaths from Coronavirus as of 29 March.

A preliminary study in the US 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.

OTHER ANIMALS

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 (diarrhea, 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.

In March 2020, researchers from the University of Hong Kong have shown that Syrian hamsters could be a model organism for COVID-19 research.

RESEARCH

No medication or vaccine is approved with the specific indication to treat the disease. International research on vaccines and medicines in COVID‑19 is underway by government organizations, academic groups, and industry researchers. In March, the World Health Organization 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 minimize 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.

VACCINE

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. Six vaccination strategies are being investigated. Four of these, as of early July 2020, are being tested in clinical trials. First, researchers aim to build a whole virus vaccine. The use of such inactive virus 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 sensitizes 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). Fourthly, scientists are attempting to use viral vectors to deliver the SARS-CoV-2 antigen gene into the cell. These can be replicating or non-replicating. As of early July 2020, only non-replicating viral vectors are in clinical trials. Viral vectors in clinical trials include Chimpanzee Adenovirus 63, Adenovirus type-5, and Adenovirus type-26. Scientists are also working to develop an attenuated COVID-19 vaccine and a COVID-19 vaccine using virus-like particles, but these are still in preclinical research. 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 the genetic code of the spike of the virus that causes the disease.

Antibody-dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.

MEDICATIONS

At least 29 phase II–IV efficacy trials in COVID‑19 were concluded in March 2020, or scheduled to provide results in April from hospitals in China. There are more than 300 active clinical trials underway as of April 2020. Seven trials were evaluating already approved treatments, including four studies on hydroxychloroquine or chloroquine. Repurposed antiviral drugs make up most of the research, with nine phase III trials on remdesivir across several countries due to report by the end of April. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.

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 standardized and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication.

Several existing medications are being evaluated for the treatment of COVID‑19, including remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir combined with interferon beta. There is tentative evidence for efficacy by remdesivir, and on 1 May 2020, the United States Food and Drug Administration (FDA) gave the drug an emergency use authorization for people hospitalized with severe COVID‑19. Phase III clinical trials for several drugs are underway in several countries, including the US, China, and Italy.

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. One study has shown an association between hydroxychloroquine or chloroquine use with higher death rates along with other side effects. A retraction of this study by its authors was published by The Lancet on 4 June 2020. 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. On 15 June 2020, the FDA updated the fact sheets for the emergency use authorization of remdesivir to warn that using chloroquine or hydroxychloroquine with remdesivir may reduce the antiviral activity of remdesivir.

Initial clinical trial results of dexamethasone in the United Kingdom released in June showed a reduction of mortality of one third for patients who are critically ill on ventilators and one fifth for those on oxygen in a randomized trial involving 11,500 patients and six treatments. Because this is a well-tested and widely available treatment this was welcomed by the WHO.

CYTOKINE STORM

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 phase 2 non-randomized 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-6 receptor antagonist was approved by the Food and Drug Administration (FDA) to undergo a phase III clinical trial assessing 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 cell therapy, in 2017. To date, there is no randomized, 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 hospitalized patients with COVID‑19.

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

PASSIVE ANTIBODIES

Development of neutralizing antibodies for treating COVID-19. In the receptor binding stage, the S1 subunit of SARS-CoV-2 binds human ACE2 on the host cell surface. Antibodies that bind the RBD domain on the S1 subunit might block the interaction of the RBD and the ACE2. In the viral fusion stage, after the cleavage of S1 subunit, the viral fusion peptide (FP) on the S2 subunit inserts into the host cell membrane, inducing the conformational change of the S2 subunit, which forms a six-helix bundle (6-HB) with the HR1 and HR2 trimers. Antibodies that target the HR domains might block viral fusion. Ab, antibody

Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of passive immunization. This strategy was tried for SARS with inconclusive results. Viral neutralization is the anticipated mechanism of action by which passive antibody therapy can mediate defense against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for neutralizing antibodies. It has been proposed that selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may 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.