Corona Virus Disease-19 (COVID-19) Outbreak

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INTRODUCTION:
Virus, an infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The name is from a Latin word meaning “slimy liquid” or “poison.” The earliest indications of the biological nature of viruses came from studies in 1892 by the Russian scientist Dmitry I. Ivanovsky and in 1898 by the Dutch scientist Martinus W. Beijerinck. Beijerinck first surmised that the virus under study was a new kind of infectious agent, which he designated contagium vivum fluidum, meaning that it was a live, reproducing organism that differed from other organisms.
Viruses occupy a special taxonomic position: they are not plants, animals, or prokaryotic bacteria (single-cell organisms without defined nuclei), and they are generally placed in their own kingdom. In fact, viruses should not even be considered organisms, in the strictest sense, because they are not free-living, i.e., they cannot reproduce and carry on metabolic processes without a host cell.

All true viruses contain nucleic acid—either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid)—and protein. The nucleic acid encodes the genetic information unique for each virus. The infective, extracellular (outside the cell) form of a virus is called the virion. It contains at least one unique protein synthesized by specific genes in the nucleic acid of that virus. In virtually all viruses, at least one of these proteins forms a shell (called a capsid) around the nucleic acid. Certain viruses also have other proteins internal to the capsid; some of these proteins act as enzymes, often during the synthesis of viral nucleic acids. Viroids (meaning “virus like”) are disease-causing organisms that contain only nucleic acid and have no structural proteins. Other virus like particles called prions are composed primarily of a protein tightly complexed with a small nucleic acid molecule. Prions are very resistant to inactivation and appear to cause degenerative brain disease in mammals, including humans.
Viruses are quintessential parasites; they depend on the host cell for almost all of their life-sustaining functions. Unlike true organisms, viruses cannot synthesize proteins, because they lack ribosomes (cell organelles) for the translation of viral messenger RNA (mRNA; a complimentary copy of the nucleic acid of the nucleus that associates with ribosomes and directs protein synthesis) into proteins. Viruses must use the ribosomes of their host cells to translate viral mRNA into viral proteins.
The virion capsid has three functions: (1) to protect the viral nucleic acid from digestion by certain enzymes (nucleases), (2) to furnish sites on its surface that recognize and attach (adsorb) the virion to receptors on the surface of the host cell, and, in some viruses, (3) to provide proteins that form part of a specialized component that enables the virion to penetrate through the cell surface membrane or, in special cases, to inject the infectious nucleic acid into the interior of the host cell.


GENERAL STRUCTURE OF VIRUS

CORONA VIRUS:
Coronavirus (CoV) is a large family of positive-sense, single-stranded RNA viruses that belong to the Nidovirales order. The order includes Roniviridae, Arteriviridae, and Coronaviridae families. The Coronaviridae family is subdivided into Torovirinae and Coronavirinae subfamilies. Coronavirinae is further subclassified into alpha-, beta-, gamma-, and delta-COVs. Phylogenetic clustering accounts for the classification of these subtypes of viruses.
The name “coronavirus,” coined in 1968, is derived from the “corona”-like or crown-like morphology observed for these viruses in the electron microscope. In 1975, the Coronaviridae family was established by the International Committee on the Taxonomy of Viruses.
CORONA VIRUS DISEASE (COVID-19):
There is a new public health crisis threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019.
HISTORY:
Coronaviruses are enveloped positive sense RNA viruses ranging from 60 nm to 140 nm in diameter with spike like projections on its surface giving it a crown like appearance under the electron microscope: hence the name coronavirus. Four corona viruses namely HKU1, NL63, 229E and OC43 have been in circulation in humans, and generally cause mild respiratory disease.
There have been two events in the past two decades wherein crossover of animal beta corona viruses to humans has resulted in severe disease. The first such instance was in 2002–2003 when a new coronavirus of the β genera and with origin in bats crossed over to humans via the intermediary host of palm civet cats in the Guangdong province of China. This virus designated as severe acute respiratory syndrome coronavirus (SARS COV) affected 8422 people mostly in China and Hong Kong and caused 916 deaths (mortality rate 11%) before being contained. Almost a decade later in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV), also of bat origin, emerged in Saudi Arabia with dromedary camels as the intermediate host and affected 2494 people and caused 858 deaths (fatality rate 34%).
ORIGIN AND SPREAD OF COVID-19:
In December 2019, adults in Wuhan, capital city of Hubei province and a major transportation hub of China startedpresenting to local hospitals with severe pneumonia of unknown cause. Many of the initial cases had a common exposure to the Huanan wholesale seafood market that also traded live animals. The surveillance system (put into place after the SARS outbreak) was activated and respiratory samples of patients were sent to reference labs for etiologic investigations. On December 31st, 2019, China notified the outbreak to the World Health Organization and on 1st January the Huanan sea food market was closed. On 7th January the virus was identified as a coronavirus that had >95% homology with the bat coronavirus and > 70% similarity with the SARS- CoV. Environmental samples from the Huanan sea food market also tested positive, signifying that the virus originated from there. The number of cases started increasing exponentially, some of which did not have exposure to the live animal market, suggestive of the fact that human-to-human transmission was occurring. The first fatal case was reported on 11th Jan 2020. The massive migration of Chinese during the Chinese New Year fuelled the epidemic. Cases in other provinces of China, other countries (Thailand, Japan and South Korea in quick succession) were reported in people who were returning from Wuhan. Transmission to healthcare workers caring for patients was described on 20th Jan 2020. By 23rd January, the 11 million population of Wuhan was placed under lock down with restrictions of entry and exit from the region. Soon this lock down was extended to other cities of Hubei province. Cases of COVID-19 in countries outside China were reported in those with no history of travel to China suggesting that local human-to-human transmission was occurring in these countries. Airports in different countries including India put in screening mechanisms to detect symptomatic people returning from China and placed them in isolation and testing them for COVID-19. Soon it was apparent that the infection couldbe transmitted from asymptomatic people and also before onset of symptoms. Therefore, countries including India
who evacuated their citizens from Wuhan through special flights or had travellers returning from China, placed
all people symptomatic or otherwise in isolation for 14 days and tested them for the virus.
It is important to note that while the number of new cases has reduced in China lately, they have increased
exponentially in other countries including South Korea, Italy and Iran. Of those infected, 20% are in critical
condition, 25% have recovered. India, which had reported only 3 cases till 2/3/2020, has also seen a sudden spurt
in cases. Currently, there have been around 1 436 198 confirmed cases of coronavirus disease 2019 (COVID-
2019) and 85 522 reported deaths to date (09/04/2020) globally. India has reported 5709 active cases and 199
reported deaths till date (10/04/2020).
EPIDEMIOLOGY AND PATHOGENESIS:
All ages are susceptible. Infection is transmitted through large droplets generated during coughing and
sneezing by symptomatic patients but can also occur from asymptomatic people and before onset of symptoms.
Patients can be infectious for as long as the symptoms last and even on clinical recovery. Some people may act as
super spreaders; a UK citizen who attended a conference in Singapore infected 11 other people while staying in a
resort in the French Alps and upon return to the UK. These infected droplets can spread 1–2 m and deposit on
surfaces. The virus can remain viable on surfaces for days in favourable atmospheric conditions but are destroyed
in less than a minute by common disinfectants like sodium hypochlorite, hydrogen peroxide etc. Infection is
acquired either by inhalation of these droplets or touching surfaces contaminated by them and then touching the
nose, mouth and eyes. The virus is also present in the stool and contamination of the water supply and subsequent
transmission via aerosolization/feco oral route is also hypothesized. As per current information, transplacental
transmission from pregnant women to their fetus has not been described. However, neonatal disease due to postnatal
transmission is described. The incubation period varies from 2 to 14 d [median 5 d]. Studies have identified
angiotensin receptor 2 (ACE2) as the receptor through which the virus enters the respiratory mucosa.

CLINICAL FEATURES:
The clinical features of COVID-19 are varied, ranging from asymptomatic state to acute respiratory
distress syndrome and multi organ dysfunction. The common clinical features include fever (not in all), cough,
sore throat, headache, fatigue, headache, myalgia and breathlessness. Conjunctivitis has also been described. Thus,
they are indistinguishable from other respiratory infections. In a subset of patients, by the end of the first week
the disease can progress to pneumonia, respiratory failure and death. This progression is associated with extreme
rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα . The median
time from onset of symptoms to dyspnea was 5 d, hospitalization 7 d and acute respiratory distress syndrome
(ARDS) 8 d. The need for intensive care admission was in 25–30% of affected patients in published series.
Adverse outcomes and death are more common in the elderly and those with underlying co-morbidities (50–75%
of fatal cases). The overall case fatality rate is estimated to range between 2 and 3%.
DIAGNOSIS:
A suspect case is defined as one with fever, sore throat and cough who has history of travel to China or
other areas of persistent local transmission or contact with patients with similar travel history or those with
confirmed COVID-19 infection. However, cases may be asymptomatic or even without fever. A confirmed case is a suspect case with a positive molecular test.
Specific diagnosis is by specific molecular tests on respiratory samples (throat swab/ nasopharyngeal
swab/ sputum/ endotracheal aspirates and bronchoalveolar lavage). Virus may also be detected in the stool and in
severe cases, the blood.

The U.S. CDC has developed criteria for persons under investigation (PUI). If a person is
deemed a PUI, immediate prevention and infection control measures are undertaken. Epidemiological factors are
used to assess the requirement of testing. These include close contact with a laboratory-confirmed patient within
14 days of symptoms or travel history to an infected area within 14 days of symptom onset. The WHO
recommends collecting samples from both the upper and lower respiratory tracts.
This can be achieved through expectorated sputum, bronchoalveolar lavage, or endotracheal aspirate.
These samples are then assessed for viral RNA using polymerase chain reaction (PCR). If a positive test result is
achieved, it is recommended to repeat the test for reverification purposes. A negative test with a strong clinical
suspicion also warrants repeat testing.
TREATMENT:
Isolation remains the most effective measure for containment of COVID-19. No specific antiviral
medication or vaccine is currently available. Therefore, the treatment of COVID-19 includes symptomatic care
and oxygen therapy. Patients with mild infections require early supportive management. This can be achieved
with the use of acetaminophen, external cooling, oxygen therapy, nutritional supplements, and anti-bacterial
therapy. Critically ill patients require high flow oxygen, extracorporeal membrane oxygenation (ECMO),
glucocorticoid therapy, and convalescent plasma. The administration of systemic corticosteroids is not
recommended to treat ARDS.
ECMO should be considered in patients with refractory hypoxemia despite undergoing protective
ventilation. Patients with respiratory failure may require intubation, mechanical ventilation, high-flow nasal
oxygen, or non-invasive ventilation. Treatment of septic shock requires hemodynamic support with the
administration of vasopressors. Organ function support is necessary for patients with multiple organ dysfunction.
Therapeutically, aerosol administration of alpha-interferon (5 million units twice daily), chloroquine
phosphate, and lopinavir/ritonavir have been suggested. Other suggested anti-virals include ribavirin and abidor.
The use of three or more anti-viral drugs simultaneously is not recommended. Ongoing clinical studies suggest
that remdesivir (GS5734) can be used for prophylaxis and therapy. Furthermore, a fusion inhibitor targeting the
HR1 domain of spike protein is reported to have the potential to treat COVID-19.
PREVENTION IS BETTER THAN CURE: THIS RULE IS APT IN THIS SITUATION
Since at this time there are no approved treatments for this infection, prevention is crucial. Several
properties of this virus make prevention difficult namely, non-specific features of the disease, the infectivity even before onset of symptoms in the incubation period, transmission from asymptomatic people, long incubation
period, tropism for mucosal surfaces such as the conjunctiva, prolonged duration of the illness and transmission
even after clinical recovery.
Isolation of confirmed or suspected cases with mild illness at home is recommended. The ventilation at
home should be good with sunlight to allow for destruction of virus. Patients should be asked to wear a simple
surgical mask and practice cough hygiene. Caregivers should be asked to wear a surgical mask when in the same
room as patient and use hand hygiene every 15–20 min. he greatest risk in COVID-19 is transmission to healthcare
workers. It is important to protect healthcare workers to ensure continuity of care and to prevent transmission of
infection to other patients.
Patients should be placed in separate rooms or cohorted together. Negative pressure rooms are not
generally needed. The rooms and surfaces and equipment should undergo regular decontamination preferably with
sodium hypochlorite. Healthcare workers should be provided with fit tested N95 respirators and protective suits
and goggles. Airborne transmission precautions should be taken during aerosol generating procedures such as
intubation, suction and tracheostomies. All contacts including healthcare workers should be monitored for
development of symptoms of COVID-19. Patients can be discharged from isolation once they are afebrile for
atleast 3 d and have two consecutive negative molecular tests at 1 d sampling interval. At the community level, people should be asked to avoid crowded areas and postpone non-essential travel to places with ongoing transmission. They should be asked to practice cough hygiene by coughing in sleeve/ tissue rather than hands and practice hand hygiene frequently every 15–20 min. Patients with respiratory symptoms should be asked to use surgical masks. The use of mask by healthy people in public places has not shown to protect against respiratory viral infections and is currently not recommended by WHO.
A candidate vaccine is under development.
SPECIAL CONDITIONS AND COVID 19:
Pregnancy and Breastfeeding:
Based on available information, pregnant people seem to have the same risk as adults who are not pregnant.
Pregnant people should:
• Avoid people who are sick or who have been exposed to the virus.
• Clean your hands often using soap and water or alcohol-based hand sanitizer.
• Clean and disinfect frequently touched surfaces daily.
• A very small number of babies have tested positive for the virus shortly after birth. However, it is unknown if these babies got the virus before or after birth.
• Mother-to-child transmission of coronavirus during pregnancy is unlikely, but after birth a newborn is susceptible to person-to-person spread
• The virus has not been detected in amniotic fluid, breastmilk, or other maternal samples.
Can women with COVID-19 breastfeed?
Yes. Women with COVID-19 can breastfeed if they wish to do so. They should:
• Practice respiratory hygiene during feeding, wearing a mask where available.
• Wash hands before and after touching the baby.
• Routinely clean and disinfect surfaces they have touched
• Breastfeed safely, with good respiratory hygiene.
• Hold your newborn skin-to-skin, and
• Share a room with your baby
Can a mother touch and hold her newborn baby if she is having COVID-19?
Yes. Close contact and early, exclusive breastfeeding helps a baby to thrive. Mother should be supported to
• Breastfeed safely, with good respiratory hygiene.
• Hold your newborn skin-to-skin, and
• Share a room with your baby
Mother should wash her hands before and after touching her baby and keep all surfaces clean.

Practice Points from an Indian Perspective:
At the time of writing this article, the risk of coronavirus in India is extremely low. But that may change in the next few weeks. Hence the following is recommended:
• Healthcare providers should take travel history of all patients with respiratory symptoms, and any international travel in the past 2 weeks as well as contact with sick people who have travelled internationally.
• They should set up a system of triage of patients with respiratory illness in the outpatient department and give them a simple surgical mask to wear. They should use surgical masks themselves while examining such patients and practice hand hygiene frequently.
• Suspected cases should be referred to government designated centres for isolation and testing (in Mumbai, at this time, it is Kasturba hospital). Commercial kits for testing are not yet available in India.
• Patients admitted with severe pneumonia and acute respiratory distress syndrome should be evaluated for travel history and placed under contact and droplet isolation. Regular decontamination of surfaces should be done. They should be tested for etiology using multiplex PCR panels if logistics permit and if no pathogen is identified, refer the samples for testing for SARS-CoV-2.
• All clinicians should keep themselves updated about recent developments including global spread of the disease.
• Non-essential international travel should be avoided at this time.
• People should stop spreading myths and false information about the disease and try to allay panic and anxiety of the public.
Conclusion:
This new virus outbreak has challenged the economic, medical and public health infrastructure of China and to some extent, of other countries especially, its neighbours. Time alone will tell how the virus will impact our lives here in India. More so, future outbreaks of viruses and pathogens of zoonotic origin are likely to continue. Therefore, apart from curbing this outbreak, efforts should be made to devise comprehensive measures to prevent future outbreaks of zoonotic origin.
***STAY HOME – STAY SAFE***

Author:

DR.B. Srikanth
MDS
Periodontics & Implantology

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