CHAPTER 23

INFECTIONS
OF THE
RESPIRATOR
Y SYSTEM (E)
DR SONAL SAXENA
DR ARPITA SAXENA
VIRAL
CAUSES OF
PNEUMONIA
VIRAL PNEUMONIA–CORONAVIRUS
PNEUMONIA
 The etiology of viral pneumonia includes all the agents that
are responsible for upper respiratory infections
Viruses that cause pneumonia are:
◦ Coronavirus
Viral ◦ SARS-CoV
Pneumonia ◦
◦
MERS-CoV
SARS-CoV-2
Coronavirus pneumonia
Second most common cause of the
common cold
Thought to cause mild-to moderate
upper respiratory tract illnesses
Associated with severe lower
respiratory infections like MERS-CoV,
SARS and COVID

Fig. 23.50 Coronavirus—the spike

protein of the virus binding to the
cell membrane (Source: CDC,
PHIL, Image ID 18114)
Morphology
Spherical or pleomorphic
Enveloped, single-stranded RNA
viruses, with club-shaped peplomers
on their surface
Spike proteins: help the virus to
bind to the receptors on the target
cell membrane.
Two groups of coronaviruses
1) Acid-labile viruses (associated with
common cold-like illnesses) Fig. 23.49 Coronavirus with its structural
proteins: S (spike protein), M (membrane
2) Acid-stable viruses (associated protein), N (nucleocapsid) and E (envelope)
with human and animal protein and the genome (RNA)
gastroenteritis)
CLASSIFICATION
Four main subgroups based on their genomic structure: Alpha, Beta, Gamma, Delta
Only alpha and beta infect mammals.
Common human corona virus—HCoV-OC43, HCoV-HKU1, HCoV-229E and HCoV-NL63:
cause common cold and self-limiting upper respiratory tract infection
Coronavirus responsible for SARS - classified into three types:

1) CoV-SARS—mammalian viruses are types 1 and 2

2) Avian virus is type 3
3) The present SARS-CoV is coronavirus type 4
 Human coronavirus 229E
Human coronavirus OC43
SARS-CoV (severe acute respiratory syndrome–
Coronaviru coronavirus)
Human coronavirus NL63 (HCoV-NL63, New
s types Haven coronavirus)
infecting Human coronavirus HKU1
humans Middle East respiratory syndrome coronavirus
(MERS-CoV),
SARS-CoV2
 Outbreak of an unusual respiratory infection with
many deaths
November 2002, South China
Spreads by the inhalation droplets or aerosols of

SARS- respiratory secretions of patients (Fecal aerosols

also may be infectious).

CoV Incubation period is under 10 days

Clinical features
Fever with cough or other respiratory symptoms,
Diarrhea can be seen
Death is due to respiratory failure
chest radiograph: Pneumonic changes
 Respiratory samples and serum
Electron microscopy
Laborator Confirmed by growth in Vero cell
y culture, animal inoculation, cloning,
sequencing and histology/
diagnosis Molecular and serological tests for
rapid diagnosis
Real-time reverse transcription PCR
(real-time RTPCR)
TREATMENT
No specific therapy or prophylaxis
Vaccine prophylaxis has not been possible due
to high rate of mutation
Control: By strict isolation and quarantine
 MERS-CoV
Middle East respiratory syndrome (MERS)

First detected in Saudi Arabia in 2012

Suspected to have come from animals such as camels

Infection spreads through respiratory secretions

Another name for the virus is human corona virus emerging Middle East (HCoV-EMC), emerging corona virus in
the Middle East

Symptoms
Severe respiratory illness

Fever, cough and shortness of breath

Severe cases may have acute renal failure

Treatment
Currently, there is no vaccine to prevent the infection

Prevention: Strict isolation and barrier nursing

 COVID-19 and SARS-CoV2

December 2019: first few cases of pneumonia with severe acute

respiratory syndrome
Wuhan in the Hubei province of China.
1 March 2020, the World Health Organization (WHO) declared the
novel coronavirus (COVID-19) outbreak a global pandemic.
Strain implicated in this pandemic is a new β-coronavirus
belonging to the subgenus of coronaviridae.
It is closely related to the bat SARS-CoV
Its reservoir host is thought to be the pangolin, an ant-eating
mammal
It was found to share 79.5% of its genetic identity with the
SARSCoV, which caused the 2002–2003 epidemic.
Epidemiology
Infectivity of the virus is very high
Case fatality is lower than that of MERS-CoV
Human-to-human transmission is the main mode of spread
Pathogenesis
 Spike proteins has a variable
receptor-binding domain (RBD)
 RBD binds to the angiotensin
converting enzyme-2 (ACE-2)
receptor
 Found in the lungs and other organs
such as the heart, kidneys and
gastrointestinal tract
 Damage of the alveolar and other
cells
 Disease has an early and a late phase
Transmission and pathogenesis of SARS-CoV-2
 1. The early phase : viral replication and direct
virus-mediated tissue damage.
2. The late phase:
Infected host cells trigger an immune response.
Mediated by cytokines: tumour necrosis factor-α
Pathogene (TNF α), granulocyte-macrophage colony-
stimulating factor (GM-CSF), interleukins (IL-1, IL-
sis 6 etc.) and interferon (IFN)-γ.
In severe COVID-19: ‘cytokine storm’ immune
system overactivation, release of high levels of
cytokines, especially IL-6 and TNF-α, causing a
local and systemic inflammatory response.
 Continuous evolution of the virus with its single
nucleotide polymorphism (SNP) variants,
resulting in many lineages.

Some mutated viruses were designated VoC

(virus of concern) as they were transmitted at a
Changes in faster rate and were able to infect large number
the virus of people.

The other concern was escape mutation,

where the virus would escape the immunity
conferred by vaccination. However, most
vaccines appear to provide protection against
the mutants.
Changes in the virus
Mutants in the spike protein of SARS-CoV-2
1) B.1.1.7 (alpha)
2) B.1.351 (beta)
3) P.1 (gamma)
4) B.1.617.2 (delta)--this virus was declared a cause for concern as it
spread rapidly
5) B.1.1.529 (Omicron) was declared a virus of concern; this variant was
found to have high transmissibility but produced less severe symptoms and
hospitalisation
 Incubation period: 2 to 14 days
Person-to-person transmission
Aged ≥60 years and patients with underlying

Clinical comorbidities: increased risk of developing

severe COVID-19 infection

features Fever cough and dyspnea fatigue and muscle

pain
Mild to moderate symptoms recover
spontaneously
Severe disease--signs and symptoms of
systemic inflammatory response and develop
acute respiratory distress syndrome
Laboratory diagnosis
CT chest: Bilateral ground glass-like appearance
and consolidation.
Oropharyngeal or nasopharyngeal swabs
Molecular methods: Confirmation by nucleic
acid amplification techniques (NAAT): real-time RT-
PCR or by reverse transcriptase quantitative PCR
(RT-qPCR)
The genes coding for the following proteins are Fig. 22.46 Collection of
nasopharyngeal swab for
detected: detection of SARS-CoV-2 viral
 Nucleoprotein (N) genomes

 Envelope protein (E)

 Membrane protein (M)
 Spike protein (S)
Other confirmatory genes for the detection are:
(i) ORF (open reading frame 1a/b)
(ii) RNA-dependent RNA polymerase (RdRp)
Rapid antigen detection: Kits demonstrating
SARS-CoV- 2 nucleocapsid antigen
Serological tests
D-dimer, CRP and interleukin-6: elevated in
those infected and useful to monitor the patient
 Types of vaccines are available:

Whole virus: Inactivated or live-attenuated (e.g., COVAXIN)

Protein subunit: Fragments of spike protein subunit to trigger an

immune response; this requires an adjuvant (Novovax)
Prophylaxi
s Nucleic acid: Genetically engineered mRNA (Moderna & BNT162b2)
or DNA (nCoV) to generate a protein that itself safely prompts an
immune response
Viral vector: A virus that cannot cause disease but serves as a
platform (vector) to encode coronavirus spike proteins (S
glycoprotein) to generate an immune response.
This is done using recombinant techniques, e.g., recombinant
adenovirus with a SARS-COV-2 gene which codes for the spike
protein incorporated into its genome (COVISHIELD)
Prevention of
transmission of
infection
Spread of SARS-CoV can be prevented by infection
prevention measures.
Quarantining of individuals testing positive for SARS-
CoV- 2
In COVID care hospitals, the following preventive
measures are undertaken:
Designated sample collection centers with barriers to
avoid close contact
Biosafety level II laboratories to perform molecular tests
 Strict isolation policies, Dedicated teams of HCW
Careful Biomedical waste handling and disposal
Vaccines
Whole virus: Inactivated or live-attenuated (e.g., COVAXIN)
Protein subunit: Fragments of spike protein subunit to trigger an
immune response; this requires an adjuvant (Novovax)
Nucleic acid: Genetically engineered mRNA (Moderna &
BNT162b2) or DNA (nCoV) to generate a protein that itself safely
prompts an immune response
Viral vector: A virus that cannot cause disease but serves as a
platform (vector) to encode coronavirus spike proteins (S
glycoprotein) to generate an immune response; this is done using
recombinant techniques, e.g., recombinant adenovirus with a
SARS-COV-2 gene which codes for the spike protein incorporated
into its genome (COVISHIELD)
Treatment
Remdesivir
Lopinavir
Ritonavir
Mainstay of supportive management is aimed at
the following:
Maintaining oxygen saturation (by mechanical
ventilation)
Preventing lung damage (due to complications
produced by heightened immunological response with
steroids)
Preventing sepsis (with antibiotic prophylaxis)