Chronology of COVID-19 Pandemic – the Un-flatten Curve

The COVID-19 pandemic gripped 193 countries including certain territories, though the disease started in Wuhan city China on 17th November 2019 as pneumonia of unknown origin linked to its seafood market, the China health authorities reported it as on 31st December 2019. The coronavirus responsible for the disease is a novel stain observed in human is a spill-over from animals seems to be bats with 96% genomic resemblance indicative of an intermediary host a mammal till not known. Initially, it has considered as human-to-human transmission of infection through contact, later hypothesizing the spread through aerosol infection also. The uncertainty with the disease has little compared with past influenza as if conditions but most of the things associates with this are unpredictable. Now, more than 2 million cases found positive with 2.5 lac cases of death around the world still it is on with meagre recovery rate. The course diseases and its management become a big task for the entire globe. The entire globe is finding the solutions with historical observations and experience, including the use of antiviral, antibiotics, and anti-malarial drugs and plasma convalescent therapy beyond these placenta proteins cells, and mesenchymal stem cell therapy are being under exploration as effective means in the management of COIVD-19.

coronavirus diseases of 2019 and is a respiratory infection caused by the novel coronavirus SARS-CoV-2 [93]. The term novel coronavirus means that a new type of coronavirus that has crown-like spikes around it. Here corona stands for crown in latin [94]. Coronaviruses (CoVs) are enveloped non-segmented positive-sense RNA viruses, which are of roughly 30 kb genome surrounded by protein belonging to the family Coronaviridae and the order Nidovirales, and are broadly distributed in humans and other mammals [95]. First discovered in domestic poultry in 1965s and causes a range of respiratory, gastrointestinal, hepatic, and neurologic diseases in animal, Scientists first discovered that CoV originate among bats following the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 [96]. CoV are zoonotic viruses-that can spill-over from animals to humans [97]. As the coronavirus family grows, different strains simultaneously co-infect individual bats, turning their little bodies into virus blenders, creating new strains of every sort, some more powerful than others [98]. This process happens without making bats sick-a phenomenon that scientists have linked to bats' singular ability, among mammals, to fly [99]. The feat takes a severe toll, such that their immune systems have evolved a better way to repair cell damage and to fight off viruses without provoking further inflammation [100]. But when these viruses leap into a new species-whether a pangolin or a civet or a human-the result can be severe, sometimes deadly, sickness [101]. In 2013 Shi Zheng-Li sequenced a coronavirus found in bats, which, in January, she discovered shares 96% of its genome with SARS-CoV-2 [102]. The two viruses have a common ancestor that dates back 30 to 50 years, but the absence of a perfect match suggests that further mutation took place in other bat colonies, and then in an intermediate host [103]. Analyses of the SARS-CoV-2 genome indicate a single spill-over an event, meaning the virus jumped only once from an animal to a human, which makes it likely that the virus was circulating among people before December 2019 [104]. Researchers from South China Agricultural University declared the intermediate host of SARS-CoV-2 could be the Chinese pangolin (Manis pentadactyla) although this has not been confirmed at this date [105]. The new coronavirus is an elusive killer since people have never seen this strain before; there is much about it remains mystery [106]. Till date seven coronaviruses are known to cause disease in humans; four cause symptoms of the common cold are 229E, OC43, NL63, and HUK1, and the other three cause more serious lung infections including pneumonia are SARS-CoV (Severe Acute Respiratory Syndrome (SARS) and MERS-CoV in 2012 (Middle East Respiratory Syndrome or MERS) and SARS-CoV-2 (the current pandemic known as COVID-19) [107]. The SARS-CoV-2 is a genus Beta-coronavirus, subgenus Sarbecovirus belonging to the family of Coronaviridae [108]. Essentially a zoonotic disease, the first human coronavirus outbreak was recorded in 1965 -HCoV-229E, followed by two outbreaks of similar capacity -SARS-CoV and MERS-CoV in 2003 and 2012, respectively [109,110] SARS-CoV-2 Natural / Laboratory created: Some folks claim that the new coronavirus causing the pandemic was man-made or engineered in a lab and deliberately released to make people sick [113]. It is currently impossible to prove or disprove the theories of its origin [114]. However, since we observed the result of genomic features might explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans and it discredits that this novel coronavirus arose naturally [115,116]. China blaming as the US army may have brought the virus to Wuhan: China [117]. Luc Montagnier a Noble Laureate and French virologist has claimed that SARS-CoV-2 is man-made virus and as an industrial accident was said to have taken place in the Wuhan National Biosafety laboratory that specializes in these coronaviruses since the early 2000s [118].

Transmission of infection:
COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes (primarily contact with an infected person, or indirectly with surfaces in the immediate environments i.e., fomites (objects used on by the infected person). Initially, airborne transmission was not considered as mean for infection [122]. But, the possibility of transmission can't be ruled out under specific circumstances and settings in which procedures or support treatments that generate aerosols are performed; i.e., endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, non-invasive positivepressure ventilation, tracheostomy, and cardiopulmonary resuscitation [123]. Current research supports the possibility of spread of infection through bio-aerosols generated directly by patients' exhalation, they are referring to fine particles emitted when someone breathes that can be suspended in the air [124]. According to Linsey Marr, an aerosol scientist at Virginia Tech the health experts so far less paid importance to the possibility of transmitting covid19 infection through the air, "I think that transmission by inhalation of the virus in the air is happening, Scientists Probe How Coronavirus Might Travel Through The Air, National Research Council 2020 [125]. Since the study indicates that the aerosol and fomite transmission of SARS-CoV-2 is plausible since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed) [126,127]. SARS-CoV-2 are viable and detected up to 72 hours (3 days) on the surfaces with a median half-life of approximately 1.1 to 1.2 hours, and the longevity of viability was stable on plastic and stainless steel than on copper and cardboard [128].

Clinical presentation of COVID-19
However, COVID-19 is a respiratory illness that primarily affects lungs, and researchers reported that the virus is also damaging the Brian, heart, kidneys, intestinal tract and liver [129,130,131]. The range of organs impacted by the virus makes the progression of the disease unpredictable and further complicates the recovery process [132,133]. About 80-85% of patients suffer from mild or moderate symptoms, 15-20% of cases experience severe [134,135]. Usually it can take up to six weeks to fully recover from COVID-19, experts say, and even months in some severe cases [136,137]. The most common symptoms manifested are Fever, Fatigue, Dry cough, Anorexia, Myalgia, Dyspnoea, Sputum, and Sore throat, [ 138,139,140] Uncommon symptoms are-Confusion, Dizziness, Headache, Running nose, Haemoptysis, Foot sores, Impairment of Renal function otherwise renal failure, Myocarditis, arrhythmia, cardiac arrest, Pulmonary embolism, respiratory failure, Loss of smell and taste (olfactory and gustatory sense), Conjunctivitis, Intestinal infection leads to pain abdomen, diarrhoea and vomiting, Acute inflammation of the liver [141,142,143,144].

Placentas cell therapy for COVID19
On 7 th April 2020, according to Yaky Yanay the CEO and President of Pluristem Therapeutics Company Haifa Israel, so far they have treated 7 cases of COVID19 from Israel, and one is under treatment from America with 15-milliliter inter muscular doses of placentas protein known as PLacental eXpanded(PLX) cells [145,146]. All seven Israelis patients had survived and three soon move off ventilators, while one had shown deterioration in respiratory parameters [147]. Two of the four Israelis with multiple organ failure showed clinical recovery as well as respiratory improvement. The firm had obtained approval on a patient-by-patient basis form the regulators [148]. Researchers around the world are studying the efficacy of mesenchymal stem cell-based products and therapy, around 10 patients in China were tested and 7 shows improvement in COVID-19 infection [149]. As the whole world puts up a collective fight against the COVID-19 pandemic, some worrying news has cropped up from across Asia-patients who tested negative of the disease are being infected with the SARS-CoV-2 virus again. Such cases had been reported from South Korea, China and Japan. Researchers from China addressed the possibility of reinfection by conducting experiments on rhesus monkeys. After 28 days, they found that the oral and anal swabs of monkeys did not show the presence of the virus. Researchers at the School of Basic Medical Sciences, Fudan University, Shanghai studied blood samples from patients who had been released after treatment and found that nearly a third had low levels of antibodies. In some patients, the antibodies could not be detected at all. The titres (concentration) of antibodies varied according to age. Older patients had more antibodies than the younger ones. The study was published in medRxiv on March 30, 2020 and has not been peer-reviewed. This could mean that if the real virus cannot induce an antibody response, the weakened version used in a vaccine may not work. South Korea's Centre for Disease Control (CDC) claimed the virus reactivated in some patients. It said it would study this further. "The most likely explanation is that people have simmering virus replication for an unusually long time and this can occasionally result in late reactivation. Most available data stated that the length of virus detection varies from person to person, so it isn't surprising that some people might continue to produce the virus and get sick," says Dave O' Connor, professor at the Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison [150]. The latest news by Italian scientists on 06 May 2020, who claimed to have developed vaccine that neutralises coronavirus in human cells. As per tests conducted at Rome's infectious-disease Spallanzani Hospital, the coronavirus vaccine has antibodies generated in mice that work on human cells. All of the vaccine candidates currently being developed are based on the genetic material of DNA protein 'spike' [151]. Scientists from the University of Texas (UT) at Austin, the National Institutes of Health and Ghent University in Belgium developed a treatment that links two nanobodies isolated from a llama to create an antibody that binds to the spike protein on the coronavirus that causes COVID-19. That bond prevented the virus from invading cells, the researchers reported in the journal Cell [152]. The journal Science on April 26 reported on a clinical trial in which critically ill Covid-19 patients at Northwell Health in the New York City area were receiving nine times the heartburn dose. Interim results from 391 patients could be known in "a few weeks," according to a hospital researcher [153].

Conclusion
The coronavirus infection is a global threat, still uncertain about its intermediary host and hypothesizing different means of transmission of infection including clusters. The new strain of virus and non-availability of treatment and severely ill and critically ill case management becomes a challenge and novel interventions are under trials. As the pandemic is progressing and the number of deaths is high and recovery is negligible, hence the circumstances prevail compulsory for social distancing and lockdowns. References: