Viral Causes of

Respiratory Infections

Evalyn A. Roxas,MD, MPH, FPCP, FPSMID

Associate Professor, Department of Medical Microbiology, UP-CPH
Section of Infectious Diseases, UP-PGH

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 Learning Objectives
At the end of this session, students should be able to…
1. Discuss viral respiratory infections based on:
a. Epidemiology
b. Characteristics of the pathogen
c. Pathogenesis
d. Clinical manifestations
2. Identify common methods used in the diagnosis of viral
respiratory infections
3. Describe prevention and control measures of some viral
infections.

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Respiratory Tract

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Respiratory Viruses
• Upper Respiratory
Rhinovirus
Coronavirus
Enterovirus
Adenovirus
EBV

• Lower Respiratory
Coronavirus
Influenza
RSV
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(1) Coronavirus

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 Characteristics
• Capsid has projections
that look like a ‘crown’
• enveloped, ssRNA
• Loose, helical
nucleocapsid
• Infects humans, other
mammals and birds

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Human Coronavirus
Human coronavirus 229E

Human coronavirus OC43

SARS- CoV 2
SARS-CoV

Human Coronavirus NL63

Human coronavirus HKU1

Middle East respiratory syndrome coronavirus (MERS Co-V)

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 SARS-CoV
• SARS outbreak in 2003
– First reported in China in
February 2003
– Spread in 24 countries in
North America, South
America, Europe, Asia
– last case in April 2004
from laboratory acquired
infection
– no. of cases: 8,437
• 813 deaths reported

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 SARS-CoV: Epidemiology
What are the • Transmission
symptoms? • can survive outside
– high grade fever the body on a dry
– respiratory symptoms surface for at least 3
pneumonia to 4 hours.
– Malaise and body • Droplet spread
aches • Direct contact
– Serious shortness of – body fluid
breath

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 Laboratory Diagnosis

• Serological Testing
– IFA: Indirect fluorescent antibody
– ELISA: Enzyme-linked immunosorbent assays
• Molecular Testing
– RT-PCR: Reverse transcriptase-PCR
– Can detect infection within the first 10 days
• Culture

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 MERS-CoV
• What we know…
– Novel coronavirus of
2012
• Similarity with batCoV
http://www.cdc.gov/features/novelcoronavirus/
– Direct or indirect
connection to the Mid
East • Clinical Manifestation
– Transmission: – severe acute respiratory
illness with symptoms of
• non-sustained human fever, cough, and
transmission shortness of breath.
– Acute renal failure

WHO, Middle East respiratory syndrome coronavirus (MERS-CoV) - update !11

Disease Outbreak News, August 2013
 MERS-CoV
• novel human β-coronavirus,
• The natural host and reservoir
of MERS-CoV remain
unknown.
• illnesses ranging in severity
from the common cold to
Severe Acute Respiratory
Syndrome (SARS).

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 MERS-CoV
• Started in September 2012
• 130 laboratory- confirmed cases of
infection with MERS-CoV
• Mortality 44.6%
• SARS virus that erupted in Asia in
2003 and infected 8,273 people,
(774 death) nine percent of whom
died.
• MERS is considered a deadlier but
less- transmissible cousin of the
SARS virus
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 MERS-CoV Transmission
Non-human to human
transmission Human-to-human transmission
• not fully understood • Difficult viral transmission
• camels are likely to be a among humans
major reservoir host • Probable human-to-
– Isolation of virus strains human transmission in
which are identical to healthcare facilities
human strains
• No sustained community
transmission has been
documented

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http://www.medicalnewstoday.com/articles/
262538.php#outbreak_updates
 Countries with lab-confirmed MERS
cases
Countries in or near the Arabian Countries with travel-associated
Peninsula with MERS cases MERS cases
• Iran • Algeria • Philippines
• Jordan • Austria • Republic of
• Kuwait • China Korea
• Lebanon • Egypt • Thailand
• Oman • France • Tunisia
• Quatar • Germany • Turkey
• Saudi Arabia • Greece • United
• United Arab Emirates (UAE) • Italy Kingdom (UK)
• Yemen • Malaysia • United States
• Netherlands of America
(USA)
 Clinical Manifestation
• severe acute respiratory
illness with symptoms of:
– Fever
– Cough
– Shortness of breath
• Others: Pneumonia,
Gastrointestinal
symptoms, Acute Renal
Failure

NSTC 2015 !16

Case definitions for reporting
Confirmed case
A person with laboratory confirmation of infection with the
Middle East respiratory syndrome coronavirus (MERS-CoV).

Probable case
A person with an acute respiratory infection with clinical,
radiological, or histopathological evidence of pulmonary
parenchymal disease (e.g. pneumonia or Acute Respiratory
Distress Syndrome); AND
no possibility of laboratory confirmation for Middle East
respiratory syndrome coronavirus (MERS-CoV) either
because the patient or samples are not available for testing;
AND close contact* with a laboratory-confirmed case.

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 Diagnosis
• Polymerase Chain Reaction
(PCR)
– confirm positive cases of
MERS-CoV by means of a
sample from the patient's
respiratory tract.
• Serology
– determine if an individual has
previously been infected, by
testing for MERS-CoV http://www.medicalnewstoday.com/articles/262538.php?page=2

antibodies

NSTC 2015 !18

Testing methods
• Cell Culture (only in BSL-3 Labs)

• Electron microscopy

• RT-PCR & Sequencing

• Serology (paired sera 2-4 weeks

apart){provided reagents are
available}

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Mers-CoV rRT-PCR (Assays for laboratory confirmation of novel human
coronavirus, hCoV-EMC, Corman et al 2012) www.eurosurveillance.org

Screening- UpE (Up-stream Envelope)

Confirmation- ORF1a (Open Reading Frame

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Testing Algorithm for MERS CoV rRT-PCR

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SARS-CoV2
February 11,
2020

WHO Coronavirus disease 2019 (COVID-19)

Situation Report- 71.
 1960 Simple Coronavirus
Flu, Common Cold
2002-2003 SARS-CoV
originated in China, severe atypical
pneumonia
fever, cough, dyspnea, watery diarrhea
2012 MERS-CoV
originated in Saudi Arabia, severe atypical
pneumonia
+ gastrointestinal symptoms + acute kidney
failure
2019 nCoV
originated in Wuhan, China

Al-Osail and Al-Wazzah (2017). The history and epidemiology of Middle East
respiratory syndrome corona virus. Multidisciplinary Respiratory Medicine
12:20 DOI 10.1186/s40248-017-0101-8
How does the virus compare to SARS and MERS?
 Chen, et Al (2020). A novel coronavirus outbreak of global health concern.
Published Online January 24, 2020 https://doi.org/10.1016/ S0140-6736(20)30185-9
 nCoV MERS-CoV SARS-CoV

Natural Host Unknown at this Bats Bats

Intermediate time Camels civet, raccoon dog
Host

Transmission Close contact from camels Close contact

limited H-H

Incubation 2-10 days 2-15 days 2-14 days

Diagnosis Respiratory Swab Lower Respiratory Lower Respiratory

Serum specimen Tract RT-PCR Tract RT-PCR
RT PCR (+) antibody test
(4-fold rise)

Current PANDEMIC All cases linked to No new case

Status Arabian Peninsula, reported since
80% Saudi Arabia 2004
Comparing to SARS and MERS-CoV
SARS-CoV was transmitted MERS-CoV … from dromedary
from civet cats to humans in camels to humans in Saudi Arabia
China in 2002. in 2012.

"civet cat in cage" by Nutch Bicer is licensed "Infrared Dromedary" by Ahmed Sajjad Zaidi is licensed
under CC BY-NC-ND 2.0 under CC BY-NC-SA 2.0
How is SARS CoV 2
transmitted?

Human-to-
human
transmission is the
main mechanism of
spread
 COVID-19 Transmission

Respiratory droplet is one of the

primary mode of transmission of SARS-
CoV-2.
Respiratory droplets are particles of water plus
respiratory fluids large enough (>5-10 µm in
diameter) to fall to the ground rapidly [and not
travel beyond 6-12ft] after being produced
WHO Scientific Brief. Modes of transmission of virus causing COVID-19:implications for IPC
precaution recommendations. WHO/2019-nCoV/Sci_Brief/Transmission_modes/2020.2. 29
March 2020
 How does it spread?
1. Droplet
infection
- Nose
- Mouth

2. Contact
infection
via hands
- Eye
Can infect 2-3
- Nose
others - Mouth
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 Most infectious
around the time of ONSET
OF SYMPTOMS:

half a day before and first

1-3 days of symptoms

https://theconversation.com/how-long-are-you-infectious-when-you-have-
coronavirus-135295
COLLEGE OF PUBLIC HEALTH SEAMEO TROPMED Philippines
Regional Centre for Public Health, Hospital Administration,
University of the Philippines Manila

Environmental and Occupational Health

COLLEGE OF PUBLIC HEALTH SEAMEO TROPMED Philippines
Regional Centre for Public Health, Hospital Administration,
University of the Philippines Manila

Environmental and Occupational Health

COLLEGE OF PUBLIC HEALTH SEAMEO TROPMED Philippines
Regional Centre for Public Health, Hospital Administration,
University of the Philippines Manila

Environmental and Occupational Health

PSMID.PCCP.PCP. PRA. PCHTM. Interim Guidance on the Clinical Managem
Adult Patients with Suspected or Confirmed COVID-19 Infection. July 20 2
Time based and Symptom based Strategy for Discontinuing Patients
Isolation and Rejoining the Community (DOH, PCP, PSMID)
•Confirmed COVID-19 and symptomatic (severe or critical) :
• 21 days after symptom onset, plus at least 3 days without Sxs
• No need for a COVID 19 PCR test at the end of quarantine as long as the
patient remains asymptomatic throughout the quarantine period
•Confirmed COVID-19 and symptomatic (mild to moderate) :
•14 days after symptom onset, plus at least 3 days without symptoms
•No need for a COVID 19 PCR test at the end of quarantine as long as the
patient remains asymptomatic throughout the quarantine period
•Confirmed COVID-19 and asymptomatic:
• 14 days after the time they tested positive for COVID-19
• No need for a COVID 19 PCR test at the end of quarantine unless
immunocompromised ( a negative result is required)

COLLEGE OF PUBLIC HEALTH SEAMEO TROPMED Philippines

Regional Centre for Public Health, Hospital Administration,
University of the Philippines Manila

Environmental and Occupational Health

Is there a vaccine against
2019-nCoV?
NONE YET
High risk areas for COVID-19

C
3Cs for COVID-19
lose spaces
with insufficient ventilation
Higher risk for Covid-1

C C
onversations
in short distance
rowded conditions
with people
Ref. Government of Japan
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Infection prevention and control (IPC) measures for
COVID 19
Proper use of medical mask

❌ ❌ ❌ 43
 Proper use of mask

✔ ✔
Source: Public Health England

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 Recommendation: Hand Hygiene

Always perform
handwashing
and hand
hygiene!
Hand Hygiene
✓ Regular and thorough
handwashing with soap and
water for at least 20 seconds is
the most effective preventive
measure
✓ Alcohol-based hand rub
containing at least 70% alcohol
✓ Always wash your hands with
soap and water if your hands
are visibly dirty
 Respiratory hygiene for coughing people
• Education of health
Catch it Bin it Kill it
workers, patients
and families
• Covering mouth &
nose when coughing
or sneezing.
• HH after contact
with respiratory
secretions.
• Wear mask 48
• Avoid touching your
eyes, nose and
Influenza virus

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 Orthomyxovirus
• Influenza Viruses Type A, B and C
– Subtypes
• antigenic variations of surface glycoprotein
– hemagglutinin (HA) and neurminidase NA)

– Type A undergoes antigenic shift and

drift.
– Type B undergoes antigenic drift only
and type C is relatively stable

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 Influenza Virus
• RNA virus
• orthomyxovirus

• Major Serotypes:
– Influenza A
– Influenza B
– Influenza C

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 Influenza Viral Structure
• Enveloped, ssRNA
negative-strand virus
• segmented genome
– Influenza A and B: 8
segments
– Influenza C: 7
segments
– each segment
encodes a different
viral protein

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 Surface Glycoproteins
• Antigenic

• Special functional
importance to the virus

• Hemagglutinin and
Neuraminidase
– High frequency of
variations result in new
serologic types

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 Surface Glycoprotein
Hemagglutinin Protein
Binding to host receptor
Internalization of the virus
Facilitation of membrane-
fusion events
Target of neutralizing
antibodies
H1, H2 and H3 most
commonly associated
with human infection

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 Surface Glycoproteins
• Neuraminidase (NA)
– Hydrolyzes the mucus
on respiratory
epithelium
– Assist in viral budding
and release of virion
from cells
– N1 and N2 most
commonly associated
with human infection

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 Influenza
• Acute respiratory infection caused by Influenza
virus – three types A, B and C
• Currently viruses circulating in human population
– Influenza A (H3N2), A (H1N1) and B Strains
• All known pandemics (global outbreaks) were
caused by Influenza A
• Animal influenza viruses may affect humans in
special circumstances – Bird Flu: A (H5N1)

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 Virus Reservoirs
• Major reservoir
– Birds, swine, horses, dogs,
cats, domestic poultry
• reservoirs provide new
strains by recombination
between influenza
viruses of man, animals
and birds

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 Changing Pattern in Influenza
• characteristic that enables influenza A
viruses to cause annual epidemics, even
pandemics

– Minor changes - antigenic drift

– Major changes - antigenic shift

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 Antigenic drift

• minor mutations in the hemagglutinin antigen

• makes prior immunity less effective

• Occurs among influenza A viruses

• resulting in emergence of new variants of prevailing

strains every year

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 Antigenic shift

• occur when two separate strains of influenza infect

the same cell simultaneously
• major changes occur in surface antigens
• occurs by mutation or by reassortment
• virus strains appear more different antigenically from
previously seen strains
• changes lead to emergence of potentially pandemic
strains

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Antigenic Shift

Karl G Nicholson, John M

Wood, Maria Zambon
Lancet 2003; 362: 1733-45
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 Influenza in Past
• 1918 – A (H1N1)
– Spanish Flu : > 20 million deaths
• 1957 – A (H2N2)
– Asian Flu : > 2 million deaths
• 1968 – A (H3N2)
– Hong Kong Flu : > 2 million deaths
– Antigenic shift only in H antigen
• 2003 – Avian Influenza / Bird Flu A (H5N1)
– First human case in 1997
– Human – to – Human transmission relatively inefficient and
not sustained

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 Flu Pandemic

• avian strain named H5N1 raised

the concern of a new influenza
pandemic, after it emerged in
Asia in the 1990s

• novel flu strain evolved that

combined genes from human,
pig, and bird flu
– "swine flu" and also known as
influenza A/H1N1, emerged in
Mexico

• World Health Organization

officially declared the outbreak to
be a "pandemic" on June 11,
2009

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 Confirmed Case of A(H1N1)
• A person with an acute febrile respiratory illness
with laboratory confirmed novel influenza A
(H1N1) virus infection at WHO approved
laboratories by one or more of the following tests:
– Real Time PCR (RT PCR)
– Viral culture
– Four-fold rise in swine influenza A (H1N1) virus
specific neutralizing antibodies

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 Influenza A (H7N9)
• Circulate among birds
• recent human
outbreak
• severe manifestation
of Influenza
• Transmission:
– Animal-to-human

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 Influenza A(H7N9)
• Natural Infection • Human Infection
– Birds: Chicken, ducks • March 2013 outbreak in
– asymptomatic China
– Transmission: • laboratory confirmed cases
respiratory droplets or are commonly admitted to
contact the ICU
– Complications: septic shock,
– considered to be low respiratory failure, ARDS,
pathogenic avian refractory hypoxemia, acute renal
dysfunction, multiple organ
influenza dysfunction, rhabdomyolysis,
encephalopathy, and bacterial
and fungal infections

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http://www.who.int/influenza/human_animal_interface/influenza_h7n9/WHO_H7N9_review_31May13.pdf
 Clinical Manifestation of Influenza
• Incubation period 2 days
(range 1-4 days)

• Abrupt onset of fever, myalgia,

sore throat, nonproductive
cough, headache

• May have gastrointestinal

symptoms (nausea, vomiting
and/or diarrhea)

• Severity of illness depends on

prior experience with related
variants

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 Immunity
• Depends on immunity to previous variant
circulating in population and on relatedness of
the two variants
• most epidemics due to antigenic shifts that
produce subtypes distantly related to previous
types
• antibody against the H protein is protective while
antibody against the N protein help modify
disease severity

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 PREVENTION AND CONTROL
o Because of antigenic drift , new vaccine has to be
prepared every year
o killed vaccine
o Live-attenuated

o Because of limited supply, vaccine given

to HIGH RISK groups only:

o Children 6 mos – 18y

o Elderly
o Chronically ill
o Institutionalized as well
as healthcare professional

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VACCINE
• ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES
– CURRENTLY TRIVALENT
• type A - H1N1
• type A - H3N2
• type B
• each year choose which strain of each subtype is the best to use for
optimal protection
• For 2019:
• A/Michigan/45/2015 (H1N1);
• A/Switzerland/8060/2017 (H3N2);
• B/Colorado/06/2017–like virus
• B/Phuket/3073/2013–like virus
• For 2020:
• A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus;
• A/Hong Kong/2671/2019 (H3N2)-like virus;
• B/Washington/02/2019 (B/Victoria lineage)-like virus
• B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
 (3) Respiratory Syncytial Virus
• pleomorphic,
envelope with
surface spikes
• negative single
strand RNA
• 2 subtypes: A and B
• Pneumovirus
lack HN protein
contains glycoprotein

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 Respiratory Syncytial Virus
• Protein structures
- Glycoprotein (G protein)
- receptor for cell attachment
- Matrix (M) protein

- Fusion (F) protein

- induce syncytia in cell culture

- virus penetration and spread
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 Respiratory Syncytial Virus
• Epidemiology
– Habitat: Human reservoir
• can infect cattle, monkeys, goats, rodents
– Transmission:
• Respiratory droplets
• direct or indirect contact with respiratory secretions
– Incidence: common in children and adults
• outbreaks during fall and winter
• contagious for 3 to 8 day

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 Epidemiology
• High risk groups
– Very young infants (<6 weeks) especially premature
babies
– Older adults
– Children with bronchopulmonary dysplasia and
congenital heart disease
– Immunocompromised individuals
– SCID
– Transplant recipients
– Hematologic malignancies

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 Respiratory Syncytial Virus
• Pathogenesis
– inoculation occurs through the nose or eyes
and spreads through respiratory epithelium
• infects ciliated cells of respiratory tract
• disseminates locally
– viral replication in the peribronchiolar tissues
leads to edema, proliferation and necrosis of
the bronchioles
– collections of sloughed epithelial cells leads to
obstruction of small bronchioles and air
trapping.
Dr. M. Lota !78
 Respiratory Syncytial Virus
• Clinical Presentation
* respiratory tract infections
- bronchiolitis
- severe disease in < 1 year old

- older children and adults

-common cold

• recovery is complete
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 RSV Bronchiolitis
• primary infection is usually
symptomatic lasts 7-21 days
– starts as URI with
congestion, sore throat,
fever
– cough deepens and
becomes more prominent
• LRT involvement heralded by
increased respiratory rate and
intercostal muscle retraction
• Hospitalization rates can
approach 40% in young infants
• rarely asymptomatic
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 Respiratory Syncytial Virus

• Laboratory Diagnosis
– immunofluorescence,
enzyme immune assay
or culture
– RT-PCR assays
• High sensitivity

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Multinucleated giant cell formation in
RSV pneumonia

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Thank you for listening!

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