The Indian Journal of Pediatrics (April 2020) 87(4):281–286

https://doi.org/10.1007/s12098-020-03263-6

REVIEW ARTICLE

A Review of Coronavirus Disease-2019 (COVID-19)

Tanu Singhal1

Received: 23 February 2020 /Accepted: 25 February 2020 /Published online: 13 March 2020
# Dr. K C Chaudhuri Foundation 2020

Keywords 2019-nCOV . SARS-CoV-2 . COVID-19 . Pneumonia . Review

Abstract
There is a new public health crises 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.
There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to
date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period
ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others.
The disease is mildin most people; in some (usually the elderly and those with comorbidities), it may progress to
pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The
case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by
special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive
protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild
disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home
isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include
contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoVand Middle East respiratory
syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

Introduction Dhirubhai Ambani Hospital and Medical Research Institute,

Mumbai, India
The 2019 novel coronavirus (2019-nCoV) or the severe rapidly evolving, readers are urged to update themselves
acute respiratory syndrome corona virus 2 (SARS-CoV-2) regularly.
as it is now called, is rapidly spreading from its origin in
Wuhan City of Hubei Province of China to the rest of the
world [1]. Till 05/ 03/2020 around 96,000 cases of
coronavirus disease 2019 (COVID-19) and 3300 deaths History
have been reported [2]. India has reported 29 cases till
Coronaviruses are enveloped positive sense RNA viruses
date. Fortunately so far, children have been infrequently
ranging from 60 nm to 140 nm in diameter with spike like
affected with no deaths. But the future course of this virus
projections on its surface giving it a crown like appearance
is unknown. This article gives a bird’s eye view about this
under the electron microscope; hence the name coronavirus
new virus. Since knowledge about this virus is
[3]. Four corona viruses namely HKU1, NL63, 229E and
OC43 have been in circulation in humans, and generally
cause mild respiratory disease.
* Tanu Singhal
There have been two events in the past two decades
[email protected] wherein crossover of animal betacorona viruses to humans
has resulted in severe disease. The first such instance was
1
Department of Pediatrics and Infectious Disease, Kokilaben in 2002– 2003 when a new coronavirus of the β genera and
282 Indian J Pediatr (April 2020) 87(4):281–286
with origin in bats crossed over to humans via the the infection could be transmitted from asymptomatic
intermediary host of palm civet cats in the Guangdong people and also before onset of symptoms. Therefore,
province of China. This virus, designated as severe acute countries including India who evacuated their citizens from
respiratory syndrome coronavirus affected 8422 people Wuhan through special flights or had travellers returning
mostly in China and Hong Kong and caused 916 deaths from China, placed all people symptomatic or otherwise in
(mortality rate 11%) before being contained [4]. Almost a isolation for 14 d and tested them for the virus.
decade later in 2012, the Middle East respiratory syndrome Cases continued to increase exponentially and
coronavirus (MERS-CoV), also of bat origin, emerged in modelling studies reported an epidemic doubling time of
Saudi Arabia with dromedary camels as the intermediate 1.8 d [10]. In fact on the 12th of February, China changed
host and affected 2494 people and caused 858 deaths its definition of confirmed cases to include patients with
(fatality rate 34%) [5]. negative/ pending molecular tests but with clinical,
radiologic and epidemiologic features of COVID-19
leading to an increase in cases by 15,000 in a single day
Origin and Spread of COVID-19 [1, 2, 6] [6]. As of 05/03/2020 96,000 cases worldwide (80,000 in
China) and 87 other countries and 1 international
In December 2019, adults in Wuhan, capital city of Hubei conveyance (696, in the cruise ship Diamond Princess
province and a major transportation hub of China started parked off the coast of Japan) have been reported [2]. It is
presenting to local hospitals with severe pneumonia of important to note that while the number of new cases has
unknown cause. Many of the initial cases had a common reduced in China lately, they have increased exponentially
exposure to the Huanan wholesale seafood market that also in other countries including South Korea, Italy and Iran. Of
traded live animals. The surveillance system (put into place those infected, 20% are in critical condition, 25% have
after the SARS outbreak) was activated and respiratory recovered, and 3310 (3013 in China and 297 in other
samples of patients were sent to reference labs for etiologic countries) have died [2]. India, which had reported only 3
investigations. On December 31st 2019, China notified the cases till 2/3/ 2020, has also seen a sudden spurt in cases.
outbreak to the World Health Organization and on 1st By 5/3/2020, 29 cases had been reported; mostly in Delhi,
January the Huanan sea food market was closed. On 7th Jaipur and Agra in Italian tourists and their contacts. One
January the virus was identified as a coronavirus that had case was reported in an Indian who traveled back from
>95% homology with the bat coronavirus and > 70% Vienna and exposed a large number of school children in a
similarity with the SARSCoV. Environmental samples birthday party at a city hotel. Many of the contacts of these
from the Huanan sea food market also tested positive, cases have been quarantined.
signifying that the virus originated from there [7]. The These numbers are possibly an underestimate of the
number of cases started increasing exponentially, some of infected and dead due to limitations of surveillance and
which did not have exposure to the live animal market, testing. Though the SARS-CoV-2 originated from bats, the
suggestive of the fact that human-to-human transmission intermediary animal through which it crossed over to
was occurring [8]. The first fatal case was reportedon11th humans is uncertain. Pangolins and snakes are the current
Jan 2020. The massive migration ofChineseduring the suspects.
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 Epidemiology and Pathogenesis [10, 11]
who were returning from Wuhan. Transmission to
healthcare workers caring for patients was described on All ages are susceptible. Infection is transmitted through
20th Jan, 2020. By 23rd January, the 11 million population large droplets generated during coughing and sneezing by
of Wuhan was placed under lock down with restrictions of symptomatic patients but can also occur from
entry and exit from the region. Soon this lock down was asymptomatic people and before onset of symptoms [9].
extended to other cities of Hubei province. Cases of Studies have shown higher viral loads inthe nasal
COVID-19 in countries outside China were reported in cavityascomparedto the throatwithno difference in viral
those with no history of travel to China suggesting that burden between symptomatic and asymptomatic people
local human-to-human transmission was occurring in these [12]. Patients can be infectious for as long as the
countries [9]. Airports in different countries including symptoms last and even on clinical recovery. Some people
India put in screening mechanisms to detect symptomatic may act as super spreaders; a UK citizen who attended a
people returning from China and placed them in isolation conference in Singapore infected 11 other people while
and testing them for COVID-19. Soon it was apparent that staying in a resort in the French Alps and upon return to

Indian J Pediatr (April 2020) 87(4):281–286 283

the UK [6]. These infected droplets can spread 1–2 m and Interestingly, disease in patients outside Hubei province
deposit on surfaces. The virus can remain viable on has been reported to be milder than those from Wuhan
surfaces for days in favourable atmospheric conditions but [17]. Similarly, the severity and case fatality rate in
are destroyed in less than a minute by common patients outside China has been reported to be milder [6].
disinfectants likesodium hypochlorite, hydrogen peroxide This may either be due to selection bias wherein the cases
etc. [13]. Infection is acquired either by inhalation of these reporting from Wuhan included only the severe cases or
droplets or touching surfaces contaminated by them and due to predisposition of the Asian population to the virus
then touching the nose, mouth and eyes. The virus is also due to higher expression of ACE2 receptors on the
present in the stool and contamination of the water supply respiratory mucosa [11].
and subsequent transmission via aerosolization/ feco oral Disease in neonates, infants and children has been also
route is also hypothesized [6]. As per current information, reported to be significantly milder than their adult
transplacental transmission from pregnant women to their counterparts. In a series of 34 children admitted to a
fetus has not been described [14]. However, neonatal hospital in Shenzhen, China between January 19th and
disease due to post natal transmission is described [14]. February 7th, there were 14 males and 20 females. The
The incubation period varies from 2 to 14 d [median 5 d]. median age was 8 y 11 mo and in 28 children the infection
Studies have identified angiotensin receptor 2 (ACE 2) as was linked to a family member and 26 children had history
the receptor through which the virus enters the respiratory of travel/residence to Hubei province in China. All the
mucosa [11]. patients were either asymptomatic (9%) or had mild
The basic case reproduction rate (BCR) is estimated to disease. No severe or critical cases were seen. The most
range from 2 to 6.47 in various modelling studies [11]. In common symptoms were fever (50%) and cough (38%).
comparison, the BCR of SARS was 2 and 1.3 for pandemic All patients recovered with symptomatic therapy and there
flu H1N1 2009 [2]. were no deaths. One case of severe pneumonia and
multiorgan dysfunction in a child has also been reported
[19]. Similarly the neonatal cases that have been reported
Clinical Features [8, 15–18] have been mild [20].

The clinical features of COVID-19 are varied, ranging

from asymptomatic state to acute respiratory distress Diagnosis [21]
syndrome and multi organ dysfunction. The common
clinical features include fever (not in all), cough, sore A suspect case is defined as one with fever, sore throat and
throat, headache, fatigue, headache, myalgia and cough who has history of travel to China or other areas of
breathlessness. Conjunctivitis has also been described. persistent local transmission or contact with patients with
Thus, they are indistinguishable from other respiratory similar travel history or those with confirmed COVID-19
infections. In a subset of patients, by the end of the first infection. However cases may be asymptomatic or even
week the disease can progress to pneumonia, respiratory without fever. A confirmed case is a suspect case with a
failure and death. This progression is associated with positive molecular test.
extreme rise in inflammatory cytokines including IL2, IL7, Specific diagnosis is by specific molecular tests on
IL10, GCSF, IP10, MCP1, MIP1A, and TNFα [15]. The respiratory samples (throat swab/ nasopharyngeal swab/
median time from onset of symptoms to dyspnea was 5 d, sputum/ endotracheal aspirates and bronchoalveolar
hospitalization 7 d and acute respiratory distress syndrome lavage). Virus may also be detected in the stool and in
(ARDS) 8 d. The need for intensive care admission was in severe cases, the blood. It must be remembered that the
25–30% of affected patients in published series. multiplex PCR panels currently available do not include
Complications witnessed included acute lung injury, the COVID-19. Commercial tests are also not available at
ARDS, shock and acute kidney injury. Recovery started in present. In a suspect case in India, the appropriate sample
the 2nd or 3rd wk. The median duration of hospital stay in has to be sent to designated reference labs in India or the
those who recovered was 10 d. Adverse outcomes and National Institute of Virology in Pune. As the epidemic
death are more common in the elderly and those with progresses, commercial tests will become available. Other
underlying co-morbidities (50–75% of fatal cases). Fatality laboratory investigations are usually non specific. The
rate in hospitalized adult patients ranged from 4 to 11%. white cell count is usually normal or low. There may be
The overall case fatality rate is estimated to range between lymphopenia; a lymphocyte count <1000 has been
2 and 3% [2]. associated with severe disease. The platelet count is usually
normal or mildly low. The CRP and ESR are generally
284 Indian J Pediatr (April 2020) 87(4):281–286
elevated but procalcitonin levels are usually normal. A 25]. Detailed guidelines for critical care management for
high procalcitonin level may indicate a bacterial co- COVID-19 have been published by the WHO [26]. There
infection. The ALT/AST, prothrombin time, creatinine, D- is, as of now, no approved treatment for COVID-19.
dimer, CPK and LDH may be elevated and high levels are Antiviral drugs such as ribavirin, lopinavirritonavir have
associated with severe disease. been used based on the experience with SARS and MERS.
The chest X-ray (CXR) usually shows bilateral In a historical control study in patients with SARS, patients
infiltrates but may be normal in early disease. The CT is treated with lopinavir-ritonavir with ribavirin had better
more sensitive and specific. CT imaging generally shows outcomes as compared to those given ribavirin alone [15].
infiltrates, ground glass opacities and sub segmental In the case series of 99 hospitalized patients with
consolidation. It is also abnormal in asymptomatic patients/ COVID19 infection from Wuhan, oxygen was given to
patients with no clinical evidence of lower respiratory tract 76%, noninvasive ventilation in 13%, mechanical
involvement. In fact, abnormal CT scans have been used to ventilation in 4%, extracorporeal membrane oxygenation
diagnose COVID-19 in suspect cases with negative (ECMO) in 3%, continuous renal replacement therapy
molecular diagnosis; many of these patients had positive (CRRT) in 9%, antibiotics in 71%, antifungals in 15%,
molecular tests on repeat testing [22]. glucocorticoids in 19% and intravenous immunoglobulin
therapy in 27% [15]. Antiviral therapy consisting of
oseltamivir, ganciclovir and lopinavirritonavir was given to
Differential Diagnosis [21] 75% of the patients. The duration of non-invasive
ventilation was 4–22 d [median 9 d] and mechanical
The differential diagnosis includes all types of respiratory ventilation for 3–20 d [median 17 d]. In the case series of
viral infections [influenza, parainfluenza, respiratory children discussed earlier, all children recovered with basic
syncytial virus (RSV), adenovirus, human treatment and did not need intensive care [17].
metapneumovirus, non COVID-19 coronavirus], atypical There is anecdotal experience with use of remdeswir, a
organisms (mycoplasma, chlamydia) and bacterial broad spectrum anti RNA drug developed for Ebola in
infections. It is not possible to differentiate COVID-19 management of COVID-19 [27]. More evidence is needed
from these infections clinically or through routine lab tests. before these drugs are recommended. Other drugs proposed
Therefore travel history becomes important. However, as for therapy are arbidol (an antiviral drug available in
the epidemic spreads, the travel history will become Russia and China), intravenous immunoglobulin,
irrelevant. interferons, chloroquine and plasma of patients recovered
from COVID-19 [21, 28, 29]. Additionally,
recommendations about using traditional Chinese herbs
Treatment [21, 23] find place in the Chinese guidelines [21].

Treatment is essentially supportive and symptomatic.

The first step is to ensure adequate isolation (discussed
later) to prevent transmission to other contacts, patients and Prevention [21, 30]
healthcare workers. Mild illness should be managed at
home with counseling about danger signs. The usual Since at this time there are no approved treatments for this
principles are maintaining hydration and nutrition and infection, prevention is crucial. Several properties of this
controlling fever and cough. Routine use of antibiotics and virus make prevention difficult namely, non-specific
antivirals such as oseltamivir should be avoided in features of the disease, the infectivity even before onset of
confirmed cases. In hypoxic patients, provision of oxygen symptoms in the incubation period, transmission from
through nasal prongs, face mask, high flow nasal cannula asymptomatic people, long incubation period, tropism for
(HFNC) or non-invasive ventilation is indicated. mucosal surfaces such as the conjunctiva, prolonged
Mechanical ventilation and even extra corporeal membrane duration of the illness and transmission even after clinical
oxygen support may be needed. Renal replacement therapy recovery.
may be needed in some. Antibiotics and antifungals are Isolation of confirmed or suspected cases with mild
required if co-infections are suspected or proven. The role illness at home is recommended. The ventilation at home
of corticosteroids is unproven; while current international should be good with sunlight to allow for destruction of
consensus and WHO advocate against their use, Chinese virus. Patients should be asked to wear a simple surgical
guidelines do recommend short term therapy with low-to- mask and practice cough hygiene. Caregivers should be
moderate dose corticosteroids in COVID-19 ARDS [24,
asked to wear a surgical mask when in the same room as COVID-19 for 2 wks even if asymptomatic. However, now
patient and use hand hygiene every 15–20 min. with rapid world wide spread of the virus these travel
The greatest risk in COVID-19 is transmission to restrictions have extended to other countries. Whether
healthcare workers. In the SARS outbreak of 2002, 21% of these efforts will lead to slowing of viral spread is not
those affected were healthcare workers [31]. Till date, known.
almost 1500 healthcare workers in China have been A candidate vaccine is under development.
infected with 6 deaths. The doctor who first warned about
the virus has died too. It is important to protect healthcare
workers to ensure continuity of care and to prevent Practice Points from an Indian Perspective
transmission of infection to other patients. While COVID-
19 transmits as a droplet pathogen and is placed in At the time of writing this article, the risk of coronavirus in
Category B of infectious agents (highly pathogenic H5N1 India is extremely low. But that may change in the next
and SARS), by the China National Health Commission, few weeks. Hence the following is recommended:
infection control measures recommended are those for
category A agents (cholera, plague). Patients should be & Healthcare providers should take travel history of all
placed in separate rooms or cohorted together. Negative patients with respiratory symptoms, and any
pressure rooms are not generally needed. The rooms and international travel in the past 2 wks as well as contact
surfaces and equipment should undergo regular with sick people who have travelled internationally.
decontamination preferably with sodium hypochlorite. & They should set up a system of triage of patients with
Healthcare workers should be provided with fit tested N95 respiratory illness in the outpatient department and give
respirators and protective suits and goggles. Airborne them a simple surgical mask to wear. They should use
transmission precautions should be taken during aerosol surgical masks themselves while examining such
generating procedures such as intubation, suction and patients and practice hand hygiene frequently.
tracheostomies. All contacts including healthcare workers & Suspected cases should be referred to government
should be monitored for development of symptoms of designated centres for isolation and testing (in Mumbai,
COVID-19. Patients can be discharged from isolation once at this time, it is Kasturba hospital). Commercial kits
they are afebrile for atleast 3 d and have two consecutive for testing are not yet available in India.
Indian J Pediatr (April 2020) 87(4):281–286 285
negative molecular tests at 1 d sampling interval. This & Patients admitted with severe pneumonia and acute
recommendation is different from pandemic flu where respiratory distress syndrome should be evaluated for
patients were asked to resume work/school once afebrile travel history and placed under contact and droplet
for 24 h or by day 7 of illness. Negative molecular tests isolation. Regular decontamination of surfaces should
were not a prerequisite for discharge. be done. They should be tested for etiology using
At the community level, people should be asked to multiplex PCR panels if logistics permit and if no
avoid crowded areas and postpone non-essential travel to pathogen is identified, refer the samples for testing for
places with ongoing transmission. They should be asked to SARS-CoV-2.
practice cough hygiene by coughing in sleeve/ tissue rather & All clinicians should keep themselves updated about
than hands and practice hand hygiene frequently every 15– recent developments including global spread of the
20 min. Patients with respiratory symptoms should be disease.
asked to use surgical masks. The use of mask by healthy & Non-essential international travel should be avoided at
people in public places has not shown to protect against this time.
respiratory viral infections and is currently not & People should stop spreading myths and false
recommended by WHO. However, in China, the public has information about the disease and try to allay panic and
been asked to wear masks in public and especially in anxiety of the public.
crowded places and large scale gatherings are prohibited Conclusions
(entertainment parks etc). China is also considering
introducing legislation to prohibit selling and trading of This new virus outbreak has challenged the economic,
wild animals [32]. medical and public health infrastructure of China and to
The international response has been dramatic. Initially, some extent, of other countries especially, its neighbours.
there were massive travel restrictions to China and people Time alone will tell how the virus will impact our lives
returning from China/ evacuated from China are being here in India. More so, future outbreaks of viruses and
evaluated for clinical symptoms, isolated and tested for pathogens of zoonotic origin are likely to continue.
286 Indian J Pediatr (April 2020) 87(4):281–286
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