(I) Mankind has never ceased its struggle against pandemics

In December 7th, 2020, a new diagnosed case of local COVID-19 in Chengdu’s Pidu District is rapidly entering a state of war, so it’s urgent to conduct nucleic acid detection and detection in key areas. Currently, there are 12 confirmed cases.
In the context of the normalization of epidemic prevention and control, it is inevitable that sporadic cases will appear in some places.

Throughout human history, man’s struggle against pandemics has never ceased.

The Black Death around 1350 is thought to have been the deadliest plague outbreak in history, killing tens of millions of people and reducing Europe’s population by a third.
The plague has not been eradicated, and there were also cases of plague in Inner Mongolia in July 2020.

HIV, for example, first appeared in Kinshasa in 1920, spread from chimpanzees in central and western Africa to humans, and later spread around the world.
On June 6, 1981, the US Centers for Disease Control and Prevention (CDC) reported the world’s first case of HIV infection, and since then humanity has been battling the number one infectious disease for a long time.
Scientists around the world have yet to develop an effective vaccine against HIV.
The phrase “Patient zero,” as you often hear it, was accidentally coined during the AIDS epidemic.
In the early 1980s, American CDC researchers investigating the spread of AIDS in San Francisco and Los Angeles used the Letter O to refer to someone outside California.
Other researchers mistakenly interpreted the letter as the number zero, so the use of patient zero was born.

A scanning electron microscope (SEM) image of HIV-1 budding from a cultured lymphocyte in green
Richard Preston, an American non-fiction writer, wrote in The Book The Blood Epidemic: There is only one flight between civilization and the virus.
A dangerous virus from the rainforest can reach any city on earth by plane within 24 hours.
Air lines connect all the cities in the world, forming a network.
Ebola has gone online and begun its journey around the world.
Ebola virus disease is a rare, severe and often fatal disease caused by the Ebola virus in the filoviridae family, with a mortality rate of up to 90%.

The Ebola virus first emerged in two simultaneous outbreaks in 1976, one in what is now Nzara, South Sudan, and the other in The Democratic Republic of Congo, Yangbuku.
The latter occurred in a village near the Ebola River, from which the disease got its name.
The incubation period for Ebola virus disease is between 2 and 21 days, and an infected person is not contagious until he or she shows symptoms.

The structure of the Ebola virus under an electron microscope
Symptoms vary, and the typical symptoms in the early stages are a rash, fever, extreme weakness, muscle pain, headache and sore throat.
As the illness progresses, patients tend to experience vomiting and diarrhea, rashes, impaired kidney and liver function, and in some cases internal and external bleeding.
Bleeding can occur through any hole in the body, including the nose, mouth, anus, genital organs or pinholes.
Ebola is a zoonotic virus. The main route of infection is through bodily fluids such as blood, sweat, vomit, excreta, urine, saliva or semen. There is no evidence of drome infection.
Despite painstaking research by the WORLD Health Organization (WHO), no animal host capable of surviving an outbreak has been identified, and fruit bats are now considered the likely original host.

Ervebo(RVSV-ZeboV), the first vaccine available for human use, was developed by Merck and approved by the European Medicines Agency (EFDA) on November 13, 2019 and the US Food and Drug Administration (FDA) on December 19, 2019. Ervebo(RVSV-ZeboV) is a preventive vaccine for people aged 18 and over.

Pathogens are generally classified into four biosafety levels (BSL) based on their level of risk.
HIV is level 2, SARS is level 3 and Ebola is level 4.
What is the level of SARS-COV-2 that is now spreading around the world?
A pathology paper from the Royal College of Pathologists in Australia on SARS-COV-2 classification was published in December in the journal of pathology, regarding it as grade 3.
The article said that although SARS-COV-2 is a globally transmitted infection, its fatality rate is not high, ranging from 0.13% to 6.22%, far lower than that of Ebola virus (BSL4), which has a fatality rate of 90%.
Moreover, the study indicated that 86% of the patients with severe diseases are elderly people over 70 years old, among whom the elderly with cardiovascular and respiratory diseases have a higher mortality rate.
Sars-cov-2 is classified into grade 3 according to the laboratory protective equipment, virus infection rate and fatality rate.

(b) Novel Coronavirus discovery

Coronaviruses are a family of viruses found in animals and humans.
Some coronaviruses infect people and are known to cause more Severe illnesses such as colds, Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome.
The first person to identify the human coronavirus was a woman, British virologist and viral imaging specialist June Almeida.
Almeida discovered the first human coronavirus at St Thomas’s Hospital in London in 1964.
Novel Coronavirus was the virus from which British Prime Minister Boris Johnson had been cured at St Thomas’ Hospital.

In 1963, Joan Almeida was working at the Cancer Institute in Ontario, Canada
The coronavirus, which has been spreading around the world, has never been found in human beings. This is a new strain of the virus, and the symptoms of the disease are mainly caused by changes in pneumonia. Therefore, the disease was initially called “pneumonia of unknown cause” in China.
After laboratory isolation and identification, the Chinese Center for Disease Control and Prevention determined that the disease was caused by a completely new coronavirus infection, thus calling the disease “COVID-19”.
In February of this year, THE WHO renamed COVID-19 diseases of poultry.
“CO” stands for coronavirus, “VI” for virus, “D” for disease, and “19” for the first case, which appeared in 2019.

On 31 January 2020, WHO declared that the COVID-19 outbreak constituted a Public Health Emergency of International Concern (PHEIC), based on the increase in the number of infected people in China and the emergence of outbreaks in several countries.
By mid-December 2020, there were more than 74.2 million confirmed cases and 1.65 million deaths globally.

The virus is now thought to have crossed species from a wild animal to humans and then to humans during wildlife trafficking, transportation, slaughtering and other processes.

Novel Coronavirus belongs to the genus coronavirus.
At present, it is believed to be the most similar to bat BAT SEVERE respiratory syndrome related coronaviruses from Chinese Horseshoes, with over 85% homology.
The nucleotide homology with human SARS-COV reached 78%.
It is significantly different from MERS-COV, and its homology is only about 50%.
Studies have shown the presence of a variety of coronaviruses in bats, particularly horseshoes.
But most bats live in tropical and subtropical rainforests or caves, far from human life.
Thus, viruses from bats need to evolve into animals in some semi-wild state (intermediate hosts) and, after some mutation and recombination, spread to humans.
The intermediate host of SARS is civets, while the intermediate host of MERS is dromedaries.

At present, novel Coronavirus was considered as the original host of Novel Coronavirus and pangolin as the potential animal host of SARS-COV-2. The sequence similarity of -coronavirus isolated from pangolin and the strain that infected human was up to 99%.
But there can be multiple intermediate hosts.
In the early stage of infection, the detection of animal hosts can effectively control and cut off the source of infection.
Asymptomatic COVID-19 infections can also be a source of infection.
This did not happen with SARS.
Asymptomatic infected persons, without any discomfort, are difficult to be diagnosed and isolated in a timely manner and are prone to infection in the community.

(III) Novel Coronavirus infection mechanism and transmission

This novel Coronavirus epidemic has been raging around the world for about a year. Why is novel Coronavirus so contagious?

Coronaviruses are plus-stranded single-stranded RNA viruses, which are the largest RNA viruses in the genome.
Coronaviruses have been isolated and identified in a variety of avian hosts and a variety of mammals, including vertebrates such as camels, mice, bats, dogs and cattle.
The coronavirus genus is divided into four groups:,, and coronavirus genus.
The main coronaviruses that infect mammals are and coronaviruses.
The coronaviruses that infect birds are mainly from, coronaviruses.
Novel Coronavirus is currently under the genus coronavirus.

Novel Coronavirus is similar to other coronaviruses in structure. Coronavirus particles are irregular in shape with a diameter of 60-220nm and an average diameter of 100nm. They are spherical or elliptic in shape and have diversity.
The virus particle has two layers of lipid envelope.
There are three kinds of glycoproteins on the membrane surface: spike (S) protein, envelope (E) protein, and membrane (M) protein.
Membrane protein M and enveloped protein E are involved in the assembly of the virus, while spike protein S is a key protein mediating the entry of the virus into host cells.
Novel Coronavirus binds to an angiotensin converting enzyme 2 (ACE2) receptor expressed in human airway epithelium and lung parenchyma.
During this period, The S protein is like a key, which binds to the host cell ACE2 receptor and mediates the entry of the virus into the cell. Therefore, the S protein is a key glycoprotein and can also be used as a major therapeutic target.
Although the novel Coronavirus is very similar to the SARS-COV that caused SARS(Severe Acute Respiratory Syndrome), some key mutations in the S protein receptor binding domain greatly increase the binding force of the novel Coronavirus and ACE2.
This increase in binding force may be the molecular basis for higher transmissibility of COVID-19.

COVID-19
Novel Coronavirus, in addition to intrusions into the respiratory system, has shown in clinical data that a large proportion of COVID-19 patients have varying degrees of liver and kidney damage. Studies have shown that this may be related to the widespread expression of ACE2 in various organs of the human body, including the lungs, digestive system, heart, arteries, kidneys, bladder and ileum.
In addition, both Chinese and American scholars have found that ACE2 gene expression in male testis is the highest in human body, including testicular stromal cells, spermatozoal cells and renal tubular cells, suggesting that novel Coronavirus is highly likely to cause testicular injury and male infertility, which is consistent with the clinical symptoms of orchitis in some male patients.

At present, it is considered that novel coronavirus is mainly transmitted by respiratory droplets and contact transmission. In special cases, aerosol transmission and fecal-oral transmission may be involved.
Patients transmit the virus through droplets produced by coughing, sneezing and talking.
Novel Coronavirus can also deposit on the surface of articles, such as door handles, food, mobile phones, etc., infect the hands by touching them, and then touch the mucous membranes such as mouth and nose, resulting in virus infection.

The tinder effect is used to visualize the droplets produced when a man sneezes
(IV) Clinical manifestations, treatment principles and prevention of COVID-19

Based on the current epidemiological investigation, the incubation period of COVID-19 is 1-14 days, and most cases are 3-7 days.
The most common clinical symptom is fever (38.1-39 degrees Celsius at most).
Weakness and myalgia are also two common nonspecific symptoms.
Since novel Coronavirus mainly attacks the respiratory tract, cough is also a common symptom, with dry cough most common.
Breath promotion and dyspnea also occur in some moderate to severe patients.
Some patients also experience gastrointestinal symptoms, such as diarrhea.
The diagnosis of COVID-19 also requires the combination of imaging and laboratory tests.
CT scan is recommended for imaging examination. The CT images are mostly ground glass like changes, but in severe patients, lung consolidation, pleural effusion and so on May occur.
In laboratory tests, patients often have normal or reduced white blood cell count, reduced lymphocyte count, increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and normal calcitonin. Some patients can have increased levels of liver enzyme, lactic dehydrogenase (LDH), myoenzyme and myoglobin (mostly transient).
Increased troponin, D-dimer, and other inflammatory factors were observed in some patients with severe or critical diseases, and progressive decrease of peripheral lymphocytes was observed.
Pathogeny test, RT-PCR test sarS-COV-2 nucleic acid positive;
The viral genome sequencing, which is homologous to the known highly virulent SARS-COV-2, can meet the diagnostic requirements.

Suspected and confirmed cases of COVID-19 should be treated in a designated medical facility with conditions of isolation and protection.
According to the severity of the patient’s condition, bed rest should be taken, support treatment should be strengthened, and sufficient calories should be ensured.
Pay attention to the balance of water and electrolyte to maintain the stability of the internal environment;
Closely monitor vital signs, oxygen saturation, etc.
Monitoring blood routine, urine routine, CRP, biochemical index, coagulation function, arterial blood gas analysis, chest imaging, etc.
Discharge standard, temperature returned to normal for more than 3 days;
Respiratory symptoms improved significantly;
Pulmonary imaging lesions were significantly changed.
Negative nucleic acid test of respiratory tract specimens for 2 consecutive times;
When the nucleic acid test of respiratory tract specimens was negative, the fecal pathogen nucleic acid test was negative.
The total course of disease is more than 2 weeks.
The discharged patients should be followed up closely.

Symptoms of COVID-19
COVID-19 has a certain self-limitation, and most mild patients have a good prognosis, with a total course of disease of 2-3 weeks.
Deaths are more common in the elderly and in patients with chronic underlying diseases.

Clinically, there are few targeted and specific treatments for COVID-19, mainly supporting and symptomatic treatment.
Therefore, for this kind of viral diseases, prevention is more important than treatment.
For the public, wearing masks is an easy and convenient way to prevent COVID-19.
Maintain good personal hygiene and wash your hands frequently.
Cover your mouth and nose with a tissue or elbow when coughing or sneezing, keep a social distance, and keep the room ventilated.
Novel coronavirus can survive for at least 1 day or several days ona dry surface such as stainless steel or plastic, so it is important to disinfect these surfaces as well.
Novel coronavirus is sensitive to uv and heat, and novel coronavirus can inactivate the virus effectively at 56℃ for 30min, ether, 75% ethanol, chlorine-containing disinfectant, peracetic acid, chloroform and other lipid solvents, while chlorine can’t inactivate the virus effectively.

What about nucleic acid testing?

The nucleic acid determination principle is to isolate the viral nucleic acid in the respiratory tract of patients, increase the number of viral nucleic acid by polymerase chain reaction (PCR), and then detect with a fluorescent probe that can identify novel Coronavirus nucleic acid. The whole process lasts for about 2-4 hours and requires professional operation.
The technique was invented in 1983 by Kary Mullis, an American biochemist who won the 1993 Nobel Prize in chemistry.

(v) COVID-19 drugs and vaccines

Novel Coronavirus is a novel that will coexist with humanity for a long time to come.
Since the virus cannot be expected to disappear naturally, vaccines are the solution.

Vaccines:

Vaccines work in the same way, teaching the human immune system to respond to foreign viruses.
Currently, vaccines commonly used include hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, measles, mumps, rubella (MMR), poliomyelitis, rabies, etc.
Adenovirus and smallpox vaccines are only available to high-risk groups.
Smallpox was basically eradicated in 1978, rinderpest in 2010.
Except in a few countries where logistics and religious beliefs prevented vaccination, polio has been largely eradicated.

At present, scientists around the world are stepping up the research and development of COVID-19 vaccines, some of which have entered the stage of clinical trials.
China has 4 vaccine into Ⅲ phase of clinical trial, in which three is inactivated vaccines, paragraph 1 of adenovirus vector vaccine.
On November 25, it was reported that Sinopac had submitted an application to the China Food and Drug Administration for the marketing of COVID-19 vaccine.
The COVID-19 vaccines developed by the Beijing Institute of Biological Products and the Wuhan Institute of Biological Products under the China National Pharmaceutical Corporation are both inactivated vaccines.
The United Arab Emirates (UAE) has officially approved the marketing of the COVID-19 vaccine developed by Sinopac (China Pharmaceutical Group) on Dec 9.
An interim analysis of data from the final phase of the trial showed that the vaccine had an overall response rate of 86 per cent, with a serum conversion rate of 99 per cent for neutralising antibodies and 100 per cent for the prevention of moderate and severe disease, the ministry of Health said in a statement.

Pfizer’s COVID-19 vaccine, developed in conjunction with BioNTech, and Moderna’s vaccine are mRNA vaccines.
One of the world’s most promising vaccines is based on mrnmrA-based technology pioneered by Katalin Kariko, a Hungarian-american female scientist.
An mRNA vaccine does not require an actual virus to be injected into the human body. Instead, it creates a piece of RNA that triggers the same immune response in the body that makes the antibody work.
First, it is safe and has few side effects.
There is no real virus injected into the body, only an immune response, so it is impossible for a person to catch a virus from the injection, with far fewer side effects.
Second, the effectiveness is strong.
The average flu vaccine is only more than 50 percent effective.
Previously, the medical community had expected messenger RNA vaccines to be 60-70% effective.
The results of the two companies’ large-scale trials showed more than 95 percent effectiveness.
Third, rapid development and production.
While conventional vaccines take months to make and eggs to grow, mrna vaccines do not require these steps, dramatically speeding up development in just a few weeks.
On December 2nd Britain became the first country in the world to approve Pfizer’s vaccine;
On December 8th Britain became the first country in the world to start using Pfizer’s vaccine.
On December 11, the US Food and Drug Administration (FDA) approved Pfizer and BioNTech’s COVID-19 vaccine for emergency use in the US.
Pfizer’s vaccine began in the United States on December 14.
Pfizer’s vaccine began in Canada on December 15.
On December 17, the FDA approved an emergency vaccination request for Moderna inc. ‘s vaccine.

Here’s one more thing to add:

MRNA vaccine, a relatively safe new nucleic acid vaccine, is used for the first time in the world.
Molecular design and chemical modification of mRNA vaccines are currently focused on enhancing their stability and reducing their immunogenicity.
MRNA vaccine directly injects mRNA encoding S protein gene into human body, uses human cells to synthesize S protein in the body, and stimulates human body to produce antibodies.
The advantage of mRNA vaccine is that it does not need to synthesize virus or protein, the process is simple and the safety is relatively high.
The disadvantage is that vaccine development is subject to technology, the nature of the mRNA itself and other factors, the mRNA itself is very unstable, easy to degrade.

Astrazeneca and Oxford University jointly developed the novel coronavirusS vaccine with defective chimpanzee adenovirus as the carrier, will novel coronavirusS protein gene into human cells, and then produce this protein, and guide the immune system to recognize and attack the virus, stimulate the human body to produce antibodies, chimpanzee adenovirus vector can not cause disease in humans.
Adenovirus vector vaccine has the advantages of safety, high efficiency, few adverse reactions, and can be stored under normal freezing conditions (2-8 degrees Celsius).

Developing a new vaccine is a long process.
The 2014-2016 Ebola epidemic in West Africa killed more than 11,000 people.
In fact, however, scientists at Public Health Canada had been working on an Ebola vaccine as early as 2003, and it wasn’t until the Ebola outbreak that it actually entered clinical trials.
The trial ended successfully in November 2016, but it will take another three years of trials on 15,000 people before It becomes the first Ebola vaccine pre-certified by the World Health Organization on November 12, 2019.
As a rule, it can take up to 10 years from initial development to approval for a new vaccine.
However, in response to the novel Coronavirus, the world is racing against the clock to develop a safe and effective vaccine in the shortest time possible.

The availability of vaccine containers can also be a problem in the development and production of vaccines.
Vaccines are usually packed in small glass bottles.
Perhaps it’s surprising that glass bottles are a finite resource?
The answer is yes.
The glass in the vaccine bottle is a special type of glass, borosilicate glass.
The glass is high temperature resistant and chemically stable, greatly reducing potential contamination from the bottle.
Because of the huge global demand for COVID-19 vaccines, the demand for vials will also increase, which may limit the number of vaccines available on the market.
The safe storage of vaccines is another concern.
Most vaccines need to be refrigerated, and the one developed by Pfizer needs to be kept at a temperature of -70 degrees Celsius.
Such extremely low temperature storage is common in laboratories, but not in general medical centers.

Vaccines are for prevention, drugs for treatment.

In recent years, the application of antiviral drugs has developed rapidly, and antiviral drugs can act directly at different stages of virus replication.
It can interfere with the attachment of virus particles to host cell membrane or viral nucleic acid shell.
Cell receptors or factors required to inhibit viral replication;
Blocking specific virus-encoding enzymes and proteins produced in host cells that are essential for virus replication but not required for normal host cell metabolism.

Virus-specific drugs such as nucleoside analogues (fabiravir, ribavirin, Redesivir, and galidavir) may have the potential to fight SARS-COV-2.
Rna-dependent RNA polymerase (RdRp) is an important component of the coronavirus replication and transcription complex and is involved in the production of genomic and subgenomic RNA.
Nucleoside analogues in the form of adenine or guanine derivatives target RNA-dependent RNA polymerases that block the synthesis of various RNA viruses.
Remdesivir (Gilead Sciences) is an aminophosphate prodrug derived from an adenine derivative that is chemically similar to propofol tenofovir, an approved HIV reverse transcriptase inhibitor.
Reddisivir has been shown to have broad-spectrum activity against RNA viruses such as SARS-COV and Mers-CoV in cell cultures and animal models.
In clinical trials of Ebola, however, the results have not been ideal.

Host specific drugs:

The main function of INTERFERon (IFN) is to block the transcription and translation of viral RNA and thereby prevent viral replication, without interfering with the normal function of host cells.

(vi) Reflection on COVID-19

Humans have no immunity to new infectious diseases. When diseases strike, everyone is susceptible.
If not prevented and controlled, no one will be spared.

Smallpox 1.

In 1898, archaeologists discovered a mummy with a shrivelled surface and a thick layer of pus scars on the lower side of his face, neck and shoulders, each a few millimeters in diameter and yellowish in color.
The mummy is that of The ancient Egyptian pharaoh Ramses V, who died in 1157 B.C.
Ramses V may have been the earliest known victim of smallpox.
Smallpox, a disease that frightened the royal family in costume dramas.
It is said that emperor Shunzhi died of smallpox. When he was about to die, he wanted to appoint his son Fuquan as the new emperor, but after consulting with the Empress Dowager Xiaozhuang, he chose Kangxi Xuanye as the emperor.
At that time, there was a folk saying, “After giving birth to only half a child, smallpox is the whole.”
Xuanye suffered from smallpox when he was 2 years old. He suffered from smallpox and will never get smallpox again.
In ancient times, smallpox was the main cause of death in most children, and even if it survived, it left most sufferers blind, convulsed, disabled and disfigured.
Smallpox killed one in ten people in England in the 18th century and a third of children in Glasgow between 1783 and 1802, according to research.
Edward Jenner, an English doctor, was the first to invent and popularize vaccination against smallpox.
Vaccinia was widely used in various countries to prevent smallpox, which raged for more than 3,000 years in human history and finally died out in 1980.

A baby receives a polio vaccination

2. Penicillin

Penicillin refers to the molecule containing penicillane, can destroy the cell wall of bacteria and bacteria in the breeding period of bactericidal action of a class of antibiotics, is extracted from penicillium.
Diseases that used to be considered fatal, such as pneumonia, syphilis, peritonitis and tetanus, have all been overcome by penicillin.
Penicillin is the earliest humans found that antibiotics, st. Mary school of medicine at the university of London in 1928 (now at imperial college London), professor of bacteriology Alexander Fleming (1881-1955) Alexander Fleming, penicillium have antiseptic effect, found in laboratory at the university of Oxford in 1939 by Ernst burleigh, Chai En (Sir Ernst Boris Chain, 1906-1979), Howard walt Florida (Howard Walter Florey,
1898-1968) was refined by the team he led.
For this Fleming, Zayn and Florey shared the 1945 Nobel Prize in Physiology or Medicine.

Penicillin is the father of antibiotics
Although people are frightened by the outbreak of infectious diseases, as people become more aware of the existing ones, they will eventually find solutions.

As COVID-19 prevention is becoming more common, ordinary citizens should wear masks, keep a social distance, wash their hands frequently, ventilate their rooms, and use chopsticks to share meals.
If we trust science and rely on science, we will be able to meet the challenge of all kinds of infectious diseases.