Coronavirus
COVID-19 Research
Coronaviruses are a family of viruses that were discovered in the 1960s but whose origin
is still unknown. Its different types cause different illnesses, from a cold to a severe
respiratory syndrome (a severe form of pneumonia). Most coronaviruses are not
dangerous and can be treated effectively. Although they are more frequent in autumn or
winter, they can be purchased at any time of the year. The coronavirus owes its name to
the appearance it presents, since it is very similar to a crown or halo. It is a type of virus
present in both humans and animals.
FAMILY AND VIRAL STRUCTURE
Coronaviruses (CoVs) are the largest group of viruses beloning to the Nidovirales order,
which includesCoronaviridae, Arteriviridae, and Roniviridae families.
The Coronavirinae comprise one of two subfamilies in the Coronaviridae family, with
the other being the Torovirinae. The Coronavirinae are further subdivided into four
groups, the alpha, beta, gamma and delta coronaviruses. The viruses were initially
sorted into these groups based on serology but are now divided by phylogenetic
clustering.
All viruses in the Nidovirales order are enveloped, non-segmented positive-sense
RNA viruses. They all contain very large genomes for RNA viruses, with
Coronavirinae having the largest identified RNA genomes, containing approximately
30 kilobase (kb) genomes. Other common features within the Nidovirales order
include: 1) a highly conserved genomic organization, with a large replicase gene
preceding structural and accessory genes; 2) expression of many nonstructural
genes by ribosomal frame shifting; 3) several unique or unusual enzymatic activities
encoded within the large replicase- transcriptase polyprotein; and 4) expression of
downstream genes by synthesis of 3’ nested sub-genomic mRNAs. In fact, the
Nidovirales order name is derived from these nested 3’ mRNAs, as nido is Latin for
“nest”. The major differences within the Nidovirus families are in the number, type,
and sizes of the structural proteins. These differences cause significant alterations in
the structure and morphology of the nucleocapsids and virions.
VIRAL REPLICATION
Coronavirus replication entails ribosome frame shifting during genome translation, the
synthesis of both genomic and multiple subgenomic RNA species, and the assembly of
progeny virions by a pathway that is unique among enveloped RNA viruses. The
replicase gene encoding the nonstructural proteins (Nsps) occupies two-thirds of the
genome, about 20 kb, as opposed to the structural and accessory proteins, which make up
only about 10 kb of the viral genome. The 5′ end of the genome contains a leader
sequence and untranslated region (UTR) that contains multiple stem loop structures
required for RNA replication and transcription. Additionally, at the beginning of each
structural or accessory gene are transcriptional regulatory sequences (TRSs) that are
required for expression of each of these genes (see section on RNA replication). The
3′UTR also contains RNA structures required for replication and synthesis of viral RNA.
TRANSMISSION
Until now, coronaviruses have been limited to humans. The origin of these viruses is
unknown, but certain animals, such as bats, are known to act as reservoirs. As in other
viruses that cause pneumonia, when they are transmitted in humans, the infection usually
occurs through the respiratory route, through the respiratory droplets that people produce
when they cough, sneeze, or speak.
Person-to-person spread
The virus is thought to spread mainly from person-to-person.
• Between people who are in close contact with one another (within about 6 feet).
• Through respiratory droplets produced when an infected person coughs or
sneezes.
These droplets can land in the mouths or noses of people who are nearby or possibly be
inhaled into the lungs.
Can someone spread the virus without being sick?
• People are thought to be most contagious when they are most symptomatic (the
sickest).
• Some spread might be possible before people show symptoms; there have been
reports of this occurring with this new coronavirus, but this is not thought to be
the main way the virus spreads.
Spread from contact with contaminated surfaces or objects?
It may be possible that a person can get COVID-19 by touching a surface or object that
has the virus on it and then touching their own mouth, nose, or possibly their eyes, but
this is not thought to be the main way the virus spreads.
How easily the virus spreads?
How easily a virus spreads from person-to-person can vary. Some viruses are highly
contagious (spread easily), like measles, while other viruses do not spread as easily.
Another factor is whether the spread is sustained, spreading continually without stopping.
The virus that causes COVID-19 seems to be spreading easily and sustainably in the
community (“community spread”) in some affected geographic areas.
Types
• Cold coronavirus:
This variant of coronavirus corresponds to types 229E and OC43, which cause the
common symptoms of a cold, although in more severe cases they can also cause
pneumonia in the elderly or in neonates.
• Severe acute respiratory syndrome (SARS):
It is a serious form of pneumonia. It causes respiratory distress and fever higher than
38 degrees. The 2002 outbreak spread worldwide, although its frequency has always
been higher in East Asia.
• Middle East respiratory syndrome (MERS-CoV):
It causes serious respiratory problems, in addition to fever, cough and difficulty
breathing, although at first it may be asymptomatic. In the most severe cases,
expectoration of blood, diarrhea and vomiting also occur. It had its first outbreak in
2012 and since then many cases have been reported in the Middle East, although it
has also reached Europe and the United States.
• Coronavirus COVID-19:
The new coronavirus detected in late 2019, causing COVID-19, in China shows a
genetic sequence that matches that of SARS by 80%. However, at first it seems less
virulent and with a lower case fatality rate. On the other hand, its transmission has
been much higher, it has already caused several thousand more cases than SARS and,
as a consequence, the number of deaths is also much higher.
Symptoms may include:
• Fever
• Cough
• Difficulty breathing
The CDC believes, at this time, that COVID-19 symptoms could appear as little as 2 days
or up to 14 days after exposure. This is based on what has been previously observed as
the incubation period for the MERS-CoV virus.
DIFFERENT MANIFESTATIONS
The authors of the Chinese CDC report divided the clinical manifestations of the disease
by their severity:
• Mild disease: non-pneumonia and mild pneumonia; this occurred in 81% of cases.
• Severe disease: dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation
(SpO2) ≤ 93%, PaO2/FiO2 ratio or P/F [the ratio between the blood pressure of
the oxygen (partial pressure of oxygen, PaO2) and the percentage of oxygen
supplied (fraction of inspired oxygen, FiO2)] < 300, and/or lung infiltrates > 50%
within 24 to 48 hours; this occurred in 14% of cases.
• Critical disease: respiratory failure, septic shock, and/or multiple organ
dysfunction (MOD) or failure (MOF); this occurred in 5% of cases.
Data obtainable from reports and directives provided by health policy agencies, allow
dividing the clinical manifestations of the disease according to the severity of the clinical
pictures. The COVID-19 may present with mild, moderate, or severe illness. Among the
severe clinical manifestations, there are severe pneumonia, ARDS, sepsis, and septic
shock. The clinical course of the disease seems to predict a favorable trend in the
majority of patients. In a percentage still to be defined of cases, after about a week there
is a sudden worsening of clinical conditions with rapidly worsening respiratory failure
and MOD/MOF. As a reference, the criteria of the severity of respiratory insufficiency
and the diagnostic criteria of sepsis and septic shock can be used.
Uncomplicated (mild) Illness
These patients usually present with symptoms of an upper respiratory tract viral infection,
including mild fever, cough (dry), sore throat, nasal congestion, malaise, headache,
muscle pain, or malaise. Signs and symptoms of a more serious disease, such as dyspnea,
are not present. Compared to previous HCoV infections, non-respiratory symptoms such
as diarrhea are challenging to find.
Moderate Pneumonia
Respiratory symptoms such as cough and shortness of breath (or tachypnea in children)
are present without signs of severe pneumonia.
Severe Pneumonia
Fever is associated with severe dyspnea, respiratory distress, tachypnea (> 30
breaths/min), and hypoxia (SpO2 < 90% on room air). However, the fever symptom must
be interpreted carefully as even in severe forms of the disease, it can be moderate or even
absent. Cyanosis can occur in children. In this definition, the diagnosis is clinical, and
radiologic imaging is used for excluding complications.
Acute Respiratory Distress Syndrome (ARDS)
The diagnosis requires clinical and ventilatory criteria. This syndrome is suggestive of a
serious new-onset respiratory failure or for worsening of an already identified respiratory
picture. Different forms of ARDS are distinguished based on the degree of hypoxia. The
reference parameter is the PaO2/FiO2:
• Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg. In not-ventilated patients or
in those managed through non-invasive ventilation (NIV) by using positive end-
expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) ≥ 5
cmH2O.
• Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤ 200 mmHg.
• Severe ARDS: PaO2/FiO2 ≤ 100 mmHg.
When PaO2 is not available, a ratio SpO2/FiO2 ≤ 315 is suggestive of ARDS.
Chest imaging utilized includes chest radiograph, CT scan, or lung ultrasound
demonstrating bilateral opacities (lung infiltrates > 50%), not fully explained by
effusions, lobar, or lung collapse. Although in some cases, the clinical scenario and
ventilator data could be suggestive for pulmonary edema, the primary respiratory origin
of the edema is proven after the exclusion of cardiac failure or other causes such as fluid
overload. Echocardiography can be helpful for this purpose.
Sepsis
According to the International Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3), sepsis represents a life-threatening organ dysfunction caused by a deregulated
host response to suspected or proven infection, with organ dysfunction. The clinical
pictures of patients with COVID-19 and with sepsis are particularly serious, characterized
by a wide range of signs and symptoms of multiorgan involvement. These signs and
symptoms include respiratory manifestations such as severe dyspnea and hypoxemia,
renal impairment with reduced urine output, tachycardia, altered mental status, and
functional alterations of organs expressed as laboratory data of hyperbilirubinemia,
acidosis, high lactate, coagulopathy, and thrombocytopenia. The reference for the
evaluation of multiorgan damage and the related prognostic significance is the Sequential
Organ Failure Assessment (SOFA) score, which predicts ICU mortality based on lab
results and clinical data. A pediatric version of the score has also received validation.
Septic Shock
In this scenario, which is associated with increased mortality, circulatory, and
cellular/metabolic abnormalities such as serum lactate level greater than 2 mmol/L (18
mg/dL) are present. Because patients usually suffer from persisting hypotension despite
volume resuscitation, the administration of vasopressors is required to maintain a mean
arterial pressure (MAP) ≥ 65 mmHg.
