Coronavirus (The Invisible Killer) E-Book

John Abrams

• Herausgeber: Libera Publishing
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 262

Veröffentlichungsjahr: 2020

Beschreibung

Coronavirus disease (COVID-19) is a communicable disease caused by a newly discovered coronavirus. On March 11,The World Health Organization (WHO) has declared a pandemic, which causes a sickness known as COVID-19 that has spread vastly to nearly every country.The virus has killed more than 128,000 people and infested more than 2 millionThis book provides detailed information on the origin and history strain that causes COVID-19 .The countries and territories affected by and their responses, measures to manage, aid and preventing the spread of the ongoing pandemic .Detail insights are given to signs and symptoms, the causes, diagnosis that is associated with the transmission, workplace hazards, the use of medications, experimental treatments, handling and supporting mental health conditions, reinfection ,the social impact and the crusade of misinformation in the world.The manuscript answers vital questions regarding: What is the novel coronavirus?Should I be Tested for coronavirus How do you catch the coronavirus?Can coronaviruses be transmitted from person to person? What happens if you catch the coronavirus?Is there a treatment for a novel coronavirus? Why are people worried about catching the coronavirus? Is there any cure for the coronavirus?What can I do to protect myself?Why are there a lockdown within countries? What can I do to help with this pandemic? Whats the economy of world future?This disease is shifting lives across the globe and will have a lifelong effect on us allA Portion of Royalties from this book will be donated to medical charities supporting with the international response to this pandemic.

Leseprobe

CONTENTS

CONTENTS

Part One

SARS

History

Virology

Part Two

Virology

Epidemiology

Part Three

Signs and Symptoms

Cause

Transmission

Virology

Pathophysiology

Immunopathology

Diagnosis

Detection of virus using PCR tests

Detection of virus using non-PCR tests

Chest CT scans and radiographs

Detection of antibodies

Italy

Singapore

Others

Pathology

Prevention

Workplace hazard controls for COVID-19

All workplaces

Medium-risk workplaces

High-risk healthcare and mortuary workplaces

Management

Medications

Personal protective equipment

Mechanical ventilation

Acute respiratory distress syndrome

Experimental treatment

Information technology

Psychological support

Part Four

Prevention and management of mental health conditions

Reinfection

History

Epidemiology

Society and culture

US biological weapon

Anti-Muslim

Antisemitic

Spy operation

Population control scheme

Statistics

Medical

Government

Bat soup

Simpsons prediction

Corona beer misassociation

Hospital conditions

Return of wildlife

Lions freed on the streets

Research

Drug design and laboratory testing

Therapeutic candidates

Failed clinical studies

Strategies

Initiatives for clinical trials

Part Five

Vaccine

Previous coronavirus vaccine efforts

Post-infection treatments

COVID-19 drug repurposing research

Chloroquine

Anti-cytokine storm

Passive antibody therapy

Part six

Epidemiology

Cases

Deaths

Diagrams

Duration

Transmission

Virology

Viral testing

Imaging

Management

International responses

Impact

Working together

While every precaution has been taken in the preparation of this book, the publisher assumes no responsibility for errors or omissions, or for damages resulting from the use of the information contained herein.

CORONAVIRUS (THE INVISIBLE KILLER)

First edition. April 15, 2020.

Copyright © 2020 Libera Publishing.

Written by John Abrams.

Coronavirus

The Invisible Killer

John Abrams

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Part one

Severe Acute Respiratory Syndrome Coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1)is a strain of virus that causes severe acute respiratory syndrome (SARS).It is an enveloped, positive-sense, single-stranded RNA virus which infects the epithelial cells within the lungs. The virus enters the host cell by binding to the ACE2 receptor.It infects humans, bats, and palm civets.[6]

On 16 April 2003, following the outbreak of SARS in Asia and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that the coronavirus identified by a number of laboratories was the official cause of SARS. The Centers for Disease Control and Prevention (CDC) in the United States and National Microbiology Laboratory (NML) in Canada identified the SARS-CoV genome in April 2003.Scientists at Erasmus University in Rotterdam, the Netherlands demonstrated that the SARS coronavirus fulfilled Koch's postulates thereby confirming it as the causative agent. In the experiments, macaques infected with the virus developed the same symptoms as human SARS victims.

A pandemic due to novel coronavirus disease in 2019 showed many similarities to the SARS outbreak, and the viral agent was identified as yet another strain of the SARS-related coronavirus, SARS-CoV-2.

SARs

––––––––

SARS, OR SEVERE ACUTE respiratory syndrome, is the disease caused by SARS-CoV. It causes an often severe illness and is marked initially by systemic symptoms of muscle pain, headache, and fever, followed in 2–14 days by the onset of respiratory symptoms,mainly cough, dyspnea, and pneumonia. Another common finding in SARS patients is a decrease in the number of lymphocytes circulating in the blood.

In the SARS outbreak of 2003, about 9% of patients with confirmed SARS-CoV infection died.The mortality rate was much higher for those over 60 years old, with mortality rates approaching 50% for this subset of patients.

electron microscope image of SARS virion

Virus classification

(unranked):

Virus

Realm:

Riboviria

Phylum:

incertae sedis

Order:

Nidovirales

Family:

Coronaviridae

Genus:

Betacoronavirus

Species:

Severe acute respiratory syndrome-related coronavirus

Strain:

Severe acute respiratory syndrome coronavirus

Synonyms

SARS coronavirus

SARS-related coronavirus

Severe acute respiratory syndrome coronavirus

HISTORY

––––––––

ON 12 APRIL 2003, SCIENTISTS working at the Michael Smith Genome Sciences Centre in Vancouver finished mapping the genetic sequence of a coronavirus believed to be linked to SARS. The team was led by Marco Marra and worked in collaboration with the British Columbia Centre for Disease Control and the National Microbiology Laboratory in Winnipeg, Manitoba, using samples from infected patients in Toronto. The map, hailed by the WHO as an important step forward in fighting SARS, is shared with scientists worldwide via the GSC website (see below). Donald Low of Mount Sinai Hospital in Toronto described the discovery as having been made with "unprecedented speed".The sequence of the SARS coronavirus has since been confirmed by other independent groups.

In late May 2003, studies from samples of wild animals sold as food in the local market in Guangdong, China, found a strain of SARS coronavirus could be isolated from masked palm civets (Paguma sp.), but the animals did not always show clinical signs. The preliminary conclusion was the SARS virus crossed the xenographic barrier from palm civet to humans, and more than 10,000 masked palm civets were killed in Guangdong Province. The virus was also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.), and domestic cats. In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats.Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists from the Chinese Centre for Disease Control and Prevention of Hong Kong University and the Guangzhou Centre for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civets and humans, confirming claims that the virus had jumped across species.

vIROLOGY

––––––––

SARS-CORONAVIRUS FOLLOWS the replication strategy typical of the coronavirus subfamily. The primary human receptor of the virus is angiotensin-converting enzyme 2 (ACE2), first identified in 2003.

––––––––

SCANNING ELECTRON MICROGRAPH of SARS virions

Part TWO

Severe Acute Respiratory Syndrome Coronavirus 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),colloquially known as the coronavirus and previously known by the provisional name 2019 novel coronavirus (2019-nCoV),is a positive-sense single-stranded RNA virus.It causes coronavirus disease 2019 (COVID-19), a respiratory illness. SARS-CoV-2 is contagious in humans, and the World Health Organization (WHO) has designated the ongoing pandemic of COVID-19 a Public Health Emergency of International Concern.The strain was first discovered in Wuhan, China, so it is sometimes referred to as the "Wuhan virus"or "Wuhan coronavirus".Because the WHO discourages the use of names based upon locationsand to avoid confusion with the disease SARS,it sometimes refers to SARS-CoV-2 as "the COVID-19 virus" in public health communications.The general public frequently calls both SARS-CoV-2 and the disease it causes "coronavirus", but scientists typically use more precise terminology.

vIROLOGY

Infection

––––––––

HUMAN-TO-HUMAN TRANSMISSION OF SARS-CoV-2 has been confirmed during the 2019–20 coronavirus pandemic.Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft). Indirect contact via contaminated surfaces is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic and steel for up to three days, but does not survive on cardboard for more than one day or on copper for more than four hours; the virus is inactivated by soap, which destabilises its lipid bilayer.[32] Viral RNA has also been found in stool samples from infected people.

The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections.

Taxonomically, SARS-CoV-2 is a strain of Severe acute respiratory syndrome-related coronavirus (SARSr-CoV). It is believed to have zoonotic origins and has close genetic similarity to bat coronaviruses, suggesting it emerged from a bat-borne virus.[An intermediate animal reservoir such as a pangolin is also thought to be involved in its introduction to humans. The virus shows little genetic diversity, indicating that the spillover event introducing SARS-CoV-2 to humans is likely to have occurred in late 2019.

Epidemiological studies estimate each infection results in 1.4 to 3.9 new ones when no members of the community are immune and no preventive measures taken. The virus is primarily spread between people through close contact and via respiratory droplets produced from coughs or sneezes. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2).

Reservoir

––––––––

THE FIRST KNOWN INFECTIONS from the SARS-CoV-2 strain were discovered in Wuhan, China.The original source of viral transmission to humans remains unclear, as does whether the strain became pathogenic before or after the spillover event.Because many of the first individuals found to be infected by the virus were workers at the Huanan Seafood Market,it has been suggested that the strain might have originated from the market.However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections.

Research into the natural reservoir of the virus strain that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses, most originating in the Rhinolophus genus of horseshoe bats, and two viral nucleic acid sequences found in samples taken from Rhinolophus sinicus show a resemblance of 80% to SARS-CoV-2.A third viral nucleic acid sequence from Rhinolophus affinis, collected in Yunnan province and designated RaTG13, has a 96% resemblance to SARS-CoV-2.Bats are considered the most likely natural reservoir of SARS-CoV-2,but differences between the bat coronavirus and SARS-CoV-2 suggest that humans were infected via an intermediate host.

A metagenomic study published in 2019 previously revealed that SARS-CoV, the strain of the virus that causes SARS, was the most widely distributed coronavirus among a sample of Sunda pangolins.[50] On 7 February 2020, it was announced that researchers from Guangzhou had discovered a pangolin sample with a viral nucleic acid sequence "99% identical" to SARS-CoV-2.[51] When released, the results clarified that "the receptor-binding domain of the S protein of the newly discovered Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference."[52] Pangolins are protected under Chinese law, but their poaching and trading for use in traditional Chinese medicine remains common.[53][54]

Microbiologists and geneticists in Texas have independently found evidence of reassortment in coronaviruses suggesting involvement of pangolins in the origin of SARS-CoV-2.[55] However, pangolin coronaviruses found to date only share at most 92% of their whole genomes with SARS-CoV-2, making them less similar than RaTG13 to SARS-CoV-2.[56] This is insufficient to prove pangolins to be the intermediate host; in comparison, the SARS virus responsible for the 2002–2004 outbreak shared 99.8% of its genome with a known civet coronavirus.

HORSESHOE BATS are among the most likely natural reservoirs of SARS-CoV-2

Phylogenetics and Taxonomy

SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses. It is a positive-sense single-stranded RNA (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.[57]

Like the SARS-related coronavirus strain implicated in the 2003 SARS outbreak, SARS-CoV-2 is a member of the subgenus Sarbecovirus (beta-CoV lineage B).[58][59] Its RNA sequence is approximately 30,000 bases in length.SARS-CoV-2 is unique among known betacoronaviruses in its incorporation of a polybasic cleavage site, a characteristic known to increase pathogenicity and transmissibility in other viruses.[60][61]

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS-CoV-2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions;[62] the number of genomes increased to 42 by 30 January 2020.[63] A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a common ancestor", implying that the first human infection occurred in November or December 2019.[63] As of 27 March 2020, 1,495 SARS-CoV-2 genomes sampled on six continents were publicly available.[64]

On 11 February 2020, the International Committee on Taxonomy of Viruses (ICTV) announced that according to existing rules that compute hierarchical relationships among coronaviruses on the basis of five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus strain from the 2003 SARS outbreak were insufficient to make them separate viral species. Therefore, they identified 2019-nCoV as a strain of Severe acute respiratory syndrome-related coronavirus.[2]

Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2

NCBI genome ID

MN908947

Genome size

29,903 bases

Year of completion

2020

STRUCTURAL BIOLOGY

Each SARS-CoV-2 virion is approximately 50–200 nanometres in diameter.Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope.[65] The spike protein, which has been imaged at the atomic level using cryogenic electron microscopy,[66][67] is the protein responsible for allowing the virus to attach to and fuse with the membrane of a host cell.

––––––––

STRUCTURE OF A SARSR-CoV virion

––––––––

SARS-COV-2 SPIKE HOMOTRIMER WITH one protein subunit highlighted; the ACE2 binding domain is in magenta

Protein modeling experiments on the spike protein of the virus soon suggested that SARS-CoV-2 has sufficient affinity to the receptor angiotensin converting enzyme 2 (ACE2) on human cells to use them as a mechanism of cell entry.[68] By 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS-CoV-2.[69][70][71] Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.[66][72] SARS-CoV-2 may also use basigin to assist in cell entry.[73]

Digitally colourised electron micrographs of SARS-CoV-2 virions (yellow) emerging from human cells cultured in a laboratory

INITIAL SPIKE PROTEIN priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2. After a SARS-CoV-2 virion attaches to a target cell, the cell's protease TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide. The virion then releases RNA into the cell, forcing the cell to produce copies of the virus that are disseminated to infect more cells.[74][bettersourceneeded] SARS-CoV-2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response.[65]

Epidemiology

––––––––

BASED ON THE LOW VARIABILITY exhibited among known SARS-CoV-2 genomic sequences, the strain is thought to have been detected by health authorities within weeks of its emergence among the human population in late 2019. The earliest case of infection currently known is thought to have been found on 17 November 2019.[76] The virus subsequently spread to all provinces of China and to more than 150 other countries in Asia, Europe, North America, South America, Africa, and Oceania.[77] Human-to-human transmission of the virus has been confirmed in all of these regions.[78] On 30 January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the WHO,[9][79] and on 11 March 2020 the WHO declared it a pandemic.[80]

MICROGRAPH OF SARS-CoV-2 virions (red) isolated from a patient during the 2019–20 coronavirus pandemic

The basic reproduction number (R0) of the virus has been estimated to be between 1.4 and 3.9. This means that each infection from the virus is expected to result in 1.4 to 3.9 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships.[83] Many forms of preventive efforts may be employed in specific circumstances in order to reduce the propagation of the virus.

There have been about 82,000 confirmed cases of infection in mainland China.[77] While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear,[84] one mathematical model estimated that on 25 January 75,815 people were infected in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015.[85][86] Before 24 February, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province, where Wuhan is located.[87][88] As of 7 April 2020, the percentage had decreased to 4.0%.[77]

As of 7 April 2020, there have been 1,407,123 total confirmed cases of SARS-CoV-2 infection in the ongoing pandemic.[77] The total number of deaths attributed to the virus is 81,103.[77] There are 298,352 people who have recovered from confirmed infections, meaning that there are 1,027,668 active cases.[77]

Part Three

Coronavirus 2019-2020

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 December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019–20 coronavirus pandemic.Common symptoms include fever, cough and shortness of breath.Other symptoms may include fatigue, muscle pain, diarrhea, sore throat, loss of smell and abdominal pain.While the majority of cases result in mild symptoms, some progress to viral pneumonia and multi-organ failure.As of 7 April 2020, more than 1.41 millioncases have been reported in more than 200 countries and territories,resulting in more than 81,100 deaths.More than 298,000 people have recovered.[5]

The virus is mainly spread during close contact[a] and by small droplets produced when those infected cough, sneeze or talk.These droplets may also be produced during breathing; however, they rapidly fall to the ground or surfaces and are not generally spread through the air over large distances.People may also become infected by touching a contaminated surface and then their face.The virus can survive on surfaces for up to 72 hours.It is most contagious during the first three days after onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease.The time from exposure to onset of symptoms is typically around five days, but may range from two to 14 days.[9]The standard method of diagnosis is by real-time 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), covering coughs and sneezes with a tissue or inner elbow and keeping unwashed hands away from the face. The use of masks is recommended for those who suspect they have the virus and their caregivers. Recommendations for mask use by the general public vary, with some authorities recommending against their use, some recommending their use and others requiring their use. Currently, 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 Organisation (WHO) declared the 2019–20 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC)[32] on 30 January 2020 and a pandemic on 11 March 2020.Local transmission of the disease has been recorded in many countries across all six WHO regions.

Coronavirus disease 2019 (COVID-19)

Other names

"Coronavirus"

2019-nCoV acute respiratory disease

Novel coronavirus pneumonia

[2]

Symptoms of COVID-19

Pronunciation

/kəˈroʊnəˌvaɪrəs

dɪˈziːz/

,

/ˈkoʊvɪd/

Specialty

Infectious diseases

Symptoms

Fever, cough, shortness of breath, none

Complications

Pneumonia, viral sepsis, acute respiratory distress syndrome, kidney failure

Usual onset

2–14 days (typically 5) from exposure

Causes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Risk factors

Travel, viral exposure

Diagnostic method

rRT-PCR testing, CT scan

Prevention

Hand washing, quarantine, social distancing

Treatment

Symptomatic and supportive

Frequency

1,412,103confirmed cases

Deaths

81,103 (5.7% of confirmed cases)[5]

signs and symptoms

Those infected with the virus may be asymptomatic or develop flu-like symptoms, including fever, cough, fatigue 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 diarrhoea have been observed in varying percentages.Some cases in China initially presented only with chest tightness and palpitations.In March 2020 there were reports indicating that loss of the sense of smell (anosmia) may be a common symptom among those who have mild disease,[11] although not as common as initially reported. In some, the disease may progress to pneumonia, multi-organ failure and death.In those who develop severe symptoms, time from symptom onset to needing mechanical ventilation is typically eight days.

As is common with infections, there is a delay between the moment when a person is infected with the virus and the time when they develop symptoms. This is called the incubation period. The incubation period for COVID-19 is typically five to six days but may range from two to 14 days.97.5% of people who develop symptoms will do so within 11.5 days of infection.

Reports indicate that not all who are infected develop symptoms, but their role in transmission is unknown.Preliminary evidence suggests asymptomatic cases may contribute to the spread of the disease.[50] The proportion of infected people who do not display symptoms is currently unknown and being studied, with the Korea Centers for Disease Control and Prevention (KCDC) reporting that 20% of all confirmed cases remained asymptomatic during their hospital stay.[50][51] China’s National Health Commission began including asymptomatic cases in its daily cases on 1 April, of the 166 infections on that day, 130 (78%) were asymptomatic.[52

Symptom

%

Fever

88

Dry cough

68

Fatigue

38

Sputum production

33

Loss of smell

15 to 30[11]

Shortness of breath

19

Muscle or joint pain

15

Sore throat

14

Headache

14

Chills

11

Nausea or vomiting

5

Nasal congestion

5

Diarrhoea

4 to 31

Haemoptysis

0.9

Pink eyes

0.8

cause

Transmission

RESPIRATORY DROPLETS, produced when a man is sneezing

A video discussing the basic reproduction number and case fatality rate in the context of the pandemic

Some details about how the disease is spread are still being determined.The WHO and the US Centers for Disease Control and Prevention (CDC) say it is primarily spread during close contact and by small droplets produced when people cough, sneeze or talk;with close contact being within 1–3 m (3 ft 3 in–9 ft 10 in). A study in Singapore found that an uncovered cough can lead to droplets travelling up to 4.5 meters (15 feet).[53][54] A second study, produced during the 2020 pandemic, found that advice on the distance droplets could travel might be based on old 1930s research which ignored the protective effect and speed of the warm moist outbreath surrounding the droplets; it advised that droplets can travel around 7–8 metres.[55]

Respiratory droplets may also be produced while breathing out, including when talking. Though the virus is not generally airborne,[56] The National Academy of Science has suggested that bioaerosol transmission may be possible and air collectors positioned in the hallway outside of people's rooms yielded samples positive for viral RNA.[57] The droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.[58] Some medical procedures such as intubation and cardiopulmonary resuscitation (CPR) may cause respiratory secretions to be aerosolised and thus result in airborne spread.[56] It may also spread when one touches a contaminated surface, known as fomite transmission, and then touches ones eyes, nose or mouth. While there are concerns it may spread by feces, this risk is believed to be low.

The virus is most contagious when people are symptomatic; while spread may be possible before symptoms appear, this risk is low.The European Centre for Disease Prevention and Control (ECDC) says while it is not entirely clear how easily the disease spreads, one person generally infects two to three others.

The virus survives for hours to days on surfaces.Specifically, the virus was found to be detectable for one day on cardboard, for up to three days on plastic and stainless steel and for up to four hours on copper.[59] This, however, varies based on the humidity and temperature.[60][61] Surfaces may be decontaminated with a number of solutions (within one minute of exposure to the disinfectant to achieve a 4 or more log reduction), including 78–95% ethanol (alcohol used in spirits), 70–100% 2-propanol (isopropyl alcohol), the combination of 45% 2-propanol with 30% 1-propanol, 0.21% sodium hypochlorite (bleach), 0.5% hydrogen peroxide, or 0.23–7.5% povidone-iodine. Ordinary soap and detergent are also highly effective if correctly used; soap products attack the virus' fatty protective layer, deactivating it, as well as freeing them from skin and other surfaces.[62] Other solutions, such as benzalkonium chloride and chlorhexidine gluconate (a surgical disinfectant), are less effective,[63] as are products advertised as killing bacteria which have little effect on a virus.

Virology

ILLUSTRATION OF SARSR-CoV virion

Severe 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.[64] All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature.[65] Outside the human body, the virus is killed by household soap, which bursts its protective bubble.[66]

SARS-CoV-2 is closely related to the original SARS-CoV.[67] It is thought to have a zoonotic origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). In February 2020, Chinese researchers found that there is only one amino acid difference in certain parts of the genome sequences between the viruses from pangolins and those from humans, however, whole-genome comparison to date found at most 92% of genetic material shared between pangolin coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.[68]

Pathophysiology

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.[69] 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,[70][71] though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and that these hypotheses need to be tested.[72] As the alveolar disease progresses, respiratory failure might develop and death may follow.[71]

The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium[73] as well as endothelial cells and enterocytes of the small intestine.[74]

The expanding part of the lungs, pulmonary alveoli, contain two main types of functioning cells. One cell, type I, absorbs from the air, i.e. gas exchange. The other, type II, produces surfactants, which serve to keep the lungs fluid, clean, infection free, etc. COVID-19 finds a way into a surfactant producing type II cell and smothers it by reproducing COVID-19 virus within it. Each type II cell which perishes to the virus causes an extreme reaction in the lungs. Fluids, pus and dead cell material flood the lung, causing the coronavirus pulmonary disease.

Immunopathology

Although SARS-COV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, patients with severe COVID-19 have symptoms of systemic hyperinflammation. Clinical labratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.[77]

Additionally, people with COVID-19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.[78]

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.

Diagnosis

DEMONSTRATION OF A NASOPHARYNGEAL swab for COVID-19 testing

CDC rRT-PCR test kit for COVID-19[76]

The WHO has published several testing protocols for the disease.[77] The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR).[78] The test is typically done on respiratory samples obtained by a nasopharyngeal swab, however a nasal swab or sputum sample may also be used.[79] 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 laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus.[83][84] As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used. The FDA approved the first point-of-care test on 21 March 2020 for use at the end of that month.[88]

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 March 2020 review concluded that chest X-rays are of little value in early stages, whereas CT scans of the chest are useful even before symptoms occur.[66] Typical features on CT include bilateral multilobar ground-glass opacificities with a peripheral, asymmetric and posterior distribution.[66] Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling) and consolidation develop as the disease evolves.[89] As of March 2020, the American College of Radiology recommends that "CT should not be used to screen for or as a first-line test to diagnose COVID-19".[90]

Typical CT imaging findings

CT imaging of rapid progression stage

COVID-19 testing

LABORATORY TESTING FOR the respiratory coronavirus disease 2019 (COVID-19) and the associated SARS-CoV-2 virus includes methods that detect the presence of virus and those that detect antibodies produced in response to infection.

The presence of viruses in samples is confirmed by RT-PCR, which detects the coronavirus' RNA. This test is specific and is designed to only detect the RNA of the SARS-CoV-2 virus. It is used to confirm very recent or active infections.

Detection of antibodies (serology) can be used both for diagnosis and population surveillance. Antibody tests show how many people have had the disease, including those whose symptoms were minor. An accurate mortality rate of the disease and the level of herd immunity can be determined from the results of this test.

Due to limited testing, as of March 2020 no countries had reliable data on the prevalence of the virus in their population. By 23 March, no country had tested more than 3% of their population, and there are massive variations in how much testing has been done across countries.This variability also affects reported case-fatality rates.

SARS-CoV-2

(virus)

COVID-19

(disease)

Timeline[hide]

2019

November–December

2020

January

February

March

Pandemic chronology

Responses

April

Notable deaths

Locations[hide]

National responses

Evacuations

Travel restrictions

Cruise ships

By continent

Africa

Asia

Europe

North America

Oceania

South America

Lockdowns

Austria

Tyrol

China

Hubei

elsewhere

Czech Republic

France

India

Italy

Malaysia

Spain

Venezuela

Cases

Deaths

Institutions[hide]

Centers for Disease Control

China

Europe

India

South Korea

United States

Hospitals and related

Central Hospital of Wuhan

Dabie Mountain Regional Medical Centre

Huoshenshan Hospital

Leishenshan Hospital

Xinjia Express Hotel

Organizations

Coalition for Epidemic Preparedness Innovations

National Health Commission (China)

World Health Organization

Wuhan Institute of Virology