THE latest threat to global health was recently given the name COVID-19 caused by SARS-COV-2(severe acute respiratory syndrome coronavirus-2). FIRST case was reported in December 2019, in Wuhan, Hubei province, china and is rapidly spreading from Wuhan to the rest of the world. Many of the initial cases had a common exposure to the wholesale seafood market in china that also trade live animal. This virus belong to beta-corona virus and compared with SARS and MERS, this virus has high transmissibility and low mortality rate. There have been two events in the past wherein crossover of animal beta-corona viruses to humans has resulted in severe disease. First was in 2002-2003 in china and second in 2012 in Saudi Arabia. On 18 December 2020, data showed that, more than 2.29 million cases were confirmed to be infected by covid-19, more than 157,000 individual were died and more than 5, 83,000 people were recovered.
1) STRUCTURE, GENOME AND LIFE CYCLE OF COVID-19
Covid-19 is a single strand RNA virus with a diameter of 80-120nm. Six corona viruses were previously known to cause disease in humans; SARS-CoV-2(covid-19) is the seventh member of the corona virus family. Corona virus is large pleomorphic spherical particles with bulbous surface projections and its envelope consists of lipid bilayer. Inside the envelope, there is a nucleocapsid (protein shell enclosing genetic material) and it is bound to the positive-sense single-stranded RNA genome. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell. The genome size of Corona virus is one of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′ polyadenylated tail. The genome organization for a corona virus is 5′-leader-UTR-replicase/transcriptase-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3’UTR-poly (A) tail. Genome having the reading frames for the accessory proteins and their function is unique depending on the specific corona virus.
The 2019 corona virus and the SARS-corona virus share central biological properties. Genome sequence recognition rates of SARS-CoV2 and bat SARS corona virus are 96% and it implies that covid-19 might have originated from bat. Bats are considered to be the natural hosts of Covid-19 while snakes are thought to be the intermediate hosts. But some studies found no evidence for snakes and rather pangolin is the intermediate host of the SARS-CoV-2. Further, Chinese researchers found that 92% of genetic material was shared between pangolin corona virus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.
Studies have identified angiotensin receptor 2 (ACE2) as the receptor through which the virus enters the respiratory system. Covid-19 mainly recognizes the corresponding receptor on the target cell through some specific glycoprotein and then enters into the cells and causing the infection. THE glycoprotein through which it recognizes the corresponding receptors is S-GLYCOPROTEIN. COVID-19 has higher binding affinity for ACE2 than SARS-CoV and that’s why it has more rapid transmission capability in humans. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein and this allow virus to enter into the host cell by endocytosis or direct fusion of viral envelope within host membrane then genome of virus enters cell cytoplasm. The corona virus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail, which allows the RNA to attach to the host cell’s ribosome for translation and this result in formation of polyprotein. The virus’s RNA code for proteins that stay in the host cell at least three are known. One stops the host cell from sending out signals to the immune system that it’s hijacked by virus. Another forces the host cell to release the newly created virions. And another one helps the virus resist the host cell’s immunity. In replication part, the main protein for replication is the RNA-dependent RNA polymerase (RdRp) and formation of mRNAs also takes place. The replicated RNA becomes the genome of the progeny viruses. Progeny viruses are then released from the host cell by exocytosis through vesicles. THE virus copies proliferate, break out of the cells in the body.
AFTER entering the body, virus enters nasal passage and mucous membrane of throat then move to bronchial tubes. The infections can damage the air sacs of lungs and hinders the lung’s ability to oxygenate the blood and remove carbon dioxide and can fill the lungs with pus, dead cells and other fluid which cause pneumonia. Pneumonia caused by the corona virus is more severe than pneumonia caused by bacterial infection, which can be treated by antibiotic. It can further cause other organ failure and body’s immune response to infection can cause organ malfunction. As with mostly viral infection, body temperature increases to kill the viruses and WBCs ingest, destroy infected cells and create antibiotic. But different people’s immune system behaves differently. Sometime prolonged fevers degrade body’s own proteins. If an infection sufficiently damages the lungs, they will be unable to deliver oxygen to the rest of the body and to survive a patient will require a ventilator. Anything which weakens the immune system (even having drinking or lack of sleep or missed meal) can increase infection. In addition immune system creates small proteins called Cytokines that hinders the virus’s ability to replicate but over production of cytokine (know as cytokine storm) can harm body very badly.
2) SYMPTOMS AND TRANSMISSION
The WHO says that infection is transmitted through small droplets generated during coughing, talking and sneezing by symptomatic patients but can also occur from asymptomatic(infected person but don’t display any symptoms) people. The role asymptomatic carriers in transmission are not yet fully known. Infection is acquired either by inhalation of these droplets or touching surfaces contaminated by droplets (fomite transmission) which produced while breathing out and fall onto the surface and then touching the nose, mouth and eyes. The virus can survive on surfaces for hours to days. Specially, for one day on cardboard, for up to three days on plastic and stainless steel and for up to four hours on copper but this time periods also depends on humidity and temperature. The loud talking releases more droplets and uncovered cough can lead to droplets to travel more distance.
Emergency symptoms include difficulty breathing, chest pain or pressure, difficulty walking, and bluish face or lips. In some cases, disease progress to pneumonia, organ failure and death. Most common way of transmission of covid-19 is close contact and virus is not generally airborne but air transmission might be possible. Researchers detected SARS-CoV-2 in saliva, urine, digestive tract, gastrointestinal tract of covid-19 patients. All ages are susceptible to this disease. Disease in infants and children has been reported milder than the adults. Elderly citizens get easily infected by this corona virus as compared with other groups because immune system tends to weaken with age and especially male citizen with diabetes, hypertension, heart disease, etc. People should pay more attention to elderly people who might be more vulnerable to the SARS-CoV-2. No Specific information regarding infection from pregnant women to their fetus. The common observing symptoms include fever, cough, sore throat, headache, fatigue, headache, loss of smell, breathlessness whereas diarrhea and vomiting are rare. These symptoms are indistinguishable from other respiratory infections. Corona virus can cause damage to tissues and organs other than the lungs. Some COVID-19 patients have acute heart injury, secondary infection, abnormal liver function etc. The incubation period (delay between the moment when a person is infected with the virus and the time when they develop symptoms) may range from 2 to 14 days. The lungs are the organs most affected by COVID-19 because it is most abundant in ACE2. The ACE2 is also abundantly expressed in some other parts of the body such as small intestine, heart.
The WHO has published the standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). Results are available within few hours to 2 days. A case is confirmed by positive molecular test on respiratory samples. Virus may also be detected in the stool and in severe cases, the blood. In India, the suspect sample has to be sent to designated reference labs in India or the National Institute of Virology in Pune.
It is not possible to differentiate COVID-19 from respiratory viral infections through routine lab tests and that’s why travel history becomes important aspect. The white cell count is usually normal or low. Platelet count is usually normal or mildly low. Chinese researchers have published genetic sequence so that other countries could develop polymerase chain reaction (PCR) tests to detect infection.
Chest CT scans (computed tomography scan allow users to see specific area inside the object from specific angles without cutting) may be helpful to check covid-19. CT scan is more sensitive and specific. In fact abnormal CT scans are used for cases with negative molecular test, many infected people had positive molecular test on repeat testing.
Remdesivir was recently reported as antiviral drug against many RNA viruses and some researchers reveal that it can control COVID-19 effectively. Meanwhile, chloroquine was proved to be effective in treatment of COVID-19. Chloroquine and hydroxychloroquine, a drug to treat malaria and it have apparent efficacy against COVID-19 associated pneumonia. It might inhibit the release of viral RNA into host cells. Favipiravir, a drug from Japan, could keep viruses from replication. Some also believe that ACE2 protein can be targeted using hypertension drugs. Another approach is to take blood serum from people who have recovered from the virus and use it and also its antibodies as a drug. This method is effective in various viral infections but it is unclear how effective it is against SARS-COV-2. There are many types of basic vaccines, including killed viruses, weakened viruses, and parts of viruses, or viral proteins. All aim to exposes body to components of viruses so that blood cells can make antibodies. In past it has been difficult to manufacture vaccines for corona virus’s family. A lot to trial and error are involved. A new approach to form vaccine is to copy genetic material from a virus and add it to artificial nanoparticles and this makes it possible to make a vaccine based on genetic sequence. But it is unclear that such RNA vaccines are strong enough to stimulate sufficient response from immune system. Other antiviral treatment tries to slow down the virus’s spread, but there is no clarity how effective they are.
ISOLATION is most important to prevent transmission to the other people. We should maintain proper hydration and nutrition and controlling fever and cough. we should stay at home, avoid crowded places, washing hands with soap and water often for at least 20 seconds, especially after toilet or when hands are visibly dirty, before eating, and after toughing one’s nose, coughing , sneezing. This is because outside human body virus is killed by soap. If soap and water are not available than use sanitizer with at least 60% alcohol. Avoid touching eyes and nose or mouth with unwashed hands. Cover the mouth and nose with a tissue when coughing or sneezing and proper hand hygiene after cough or sneeze is encouraged social distance aim to reduce contact of infected persons with groups by closing crowded areas like schools, workplace, public gathering etc. Another method is quarantines. Many governments have recommended self quarantine for entire population like in India. Vaccine is not expected until 2021. Patients are discharged from isolation once they have two consecutive negative molecular tests with one day gap. Studies have shown that vitamin C may prevent the susceptibility of lower respiratory tract infections. Therefore a moderate amount of vitamin C may be a way to prevent covid-19. It is particularly important to enhance self-resistance.the best ways to boost personal immunity is to maintain personal hygiene, a adequate nutritional intake. The use of mask by patients with respiratory symptoms is necessary.
COVID-19 is a serious infectious disease caused by SARA-COV-2 and its most likely source is bats. This new virus outbreak has challenged the economic, medical and public health infrastructure of the whole world. This life threatening disease has posed a great threat to global health and safety, so to control the spread of it and reduce mortality as soon as possible is the most important issue. Until now the specific mechanism of virus is unknown and no specific drugs for virus have been developed. So at present it is important to control source of infection and cut of the transmission chain. We should continue research and promote development of vaccines. Time alone will tell how this virus will impact our liver here in India. More so, future outbreaks of viruses and pathogens of zoonotic origin are likely to continue. Therefore main concern is to prevent future outbreaks of zoonotic origin.
The experience gained in china and other countries offers valuable lessons that we can beat this problem together by following proper prevention methods. Currently there is no standard treatment for disease, so the best we can do to stop its transmission by protecting yourself and others around you by knowing the facts and taking appropriate precautions. We should stay informed on latest developments about covid-19 and follow advice given by your healthcare provider, your national and local public health authority. Be patient and properly maintain social distancing. It’s a ‘matter of time’ before things get back to normal in the country.