COVID-19: CORONAVIRUS DISEASE 2019

OUTLINE Mar. 11, 2020 WHO declared COVID-19 a global pandemic

I. HISTORY 1 Last pandemic declared: H1N1 influenza
II. SARS-COV-2 2 (2009)
III. EPIDEMIOLOGY 3 Apr. 3, 2020 CDC issued a recommendation that general
IV. PATHOPHYSIOLOGY 4 public, even those without symptoms, should
V. CLINICAL MANIFESTATIONS 6 begin wearing face coverings in public
VI. MANAGEMENT 10 settings
VII. PROGNOSIS 15
VIII. PREVENTION 15 PHILIPPINES
.
Disclaimer: Do not use as primary reference. Please double check with
DATE EVENTS
original sources. I am still a student, and I did my best to read, and
understand the journals, but I am prone to errors, so please correct me if Jan. 30, 2020 First case of COVID-19 in the country with a
you find wrong content. I also have not covered every journal I have 38-year-old female Chinese national
come across so please inform me too if there are facts that need to be Jan. 31, 2020 President Duterte imposes travel ban on
updated. Thanks! Chinese citizens coming from Hubei province,
and other areas in China where the virus has
Tips Before Reading: Review lessons on Pneumonia, Acute Respiratory spread
Distress Syndrome, and Mechanical Ventilation and Oxygen Therapy to
Feb. 2, 2020 First death in the Philippines, and is also the
better appreciate this trans
first death confirmed outside China (44-year-
old Chinese male)
I. HISTORY Feb. 5, 2020 First case of a Filipino citizen (also the third
Trigger Warning: Please skip if the negative news gives you anxiety. case in the Philippines)
Feb. 10, 2020 The first coronavirus patient in the Philippines
DATE EVENTS recovers
Dec. 31, 2019 27 cases of pneumonia of unknown etiology Mar. 7, 2020 First local transmission of COVID-19 was
initially reported to the WHO confirmed
First identified in Wuhan City, Hubei Province, Mar. 9, 2020 President Duterte declared a state of public
China. health emergency
Jan. 1, 2020 The Huanan Seafood Wholesale Market that Mar. 11, 2020 First local death due to coronavirus (67-year-
was identified as a suspected center of the old Filipina with no travel history outside the
outbreak closed. Philippines)
Jan. 7, 2020 The causative agent was identified from Mar. 12, 2020 President Duterte announces Metro Manila
throat swab samples conducted by the lockdown starting March 15 to be lifted on
Chinese Center for Disease Control, and April 14
Prevention Land, domestic air, and domestic sea travel
Jan. 11, 2020 First death due to new virus to and from Metro Manila suspended until
Jan. 25, 2020 First medical professional who has treated April 14
people with the virus dies (Dr. Liang Wudong) Mar. 16, 2020 President Duterte announces enhanced
Jan. 30, 2020 WHO declared COVID-19 outbreak a global community quarantine
health emergency. Mar. 17, 2020 DOH announced confirmed community-
Feb. 5, 2020 An infant tests positive for the coronavirus just based transmission
thirty hours after birth, raising concerns of Mar. 23, 2020 The House of Representatives approved
vertical transmission House Bill 6616, or Bayanihan Act
Feb. 8, 2020 China’s National Health Commission gives Mar. 24, 2020 The Senate approved Senate Bill 1481, or
the coronavirus a temporary name, Novel “Bayanihan to Heat as One Act”
Coronavirus Pneumonia or NCP Confirmed cases in the Philippines pass the
Feb 9, 2020 The death toll from the novel 500 mark
coronavirus surpasses the toll from the SARS Mar. 25, 2020 President Duterte signed Republic Act No.
epidemic of 2002-2003 11469, or Bayanihan to Heal as One Act.
Feb. 11, 2020 Coronavirus Study Group of the International Mar. 26, 2020 At least 9 doctors have died due to COVID-19
Committee on Taxonomy of Viruses - issued a Apr. 4, 2020 FDA-approved test kits developed by UP
statement announcing an official designation scientists ready for mass use
for the novel virus: severe acute respiratory Apr. 7, 2020 Luzon lockdown extended to April 30
syndrome coronavirus 2 (SARS-CoV-2) Apr. 11, 2020 DOH updates COVID-19 case categorization
Feb. 11, 2020 WHO gave the disease cause by the Apr. 13, 2020 Philippines has the most COVID-19 cases in
aforementioned virus COVID-19 short for Southeast Asia
coronavirus disease 2019 Apr. 24, 2020 ECQ extended to May 15, 2020

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 1

 II. SARS-COV 2 Feline Infectious Peritonitis Virus
(FIPV)
Feline Infectious Peritonitis (Fip)
- similarities to the human
Don’t be intimidated by the extremely molecular parts disease, Sarcoidosis
• Coronavirus disease 2019 (COVID-19) is defined as illness Bovine CoV, Rat CoV, and Mild to Severe Respiratory Tract
caused by a novel coronavirus now called severe acute Infectious Bronchitis Virus (IBV) Infections in Cattle, Rats, and
respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly Chickens
Causes Diarrhea (“Winter
called 2019-nCoV)
Dysentery” And “Shipping
• Postulated to have originated in a large animal and Fever”)
seafood market (Huanan Seafood Wholesale Market) Mesoniviridae Identified as the first Nidoviruses
to exclusively infect insect hosts
CORONAVIRUS FAMILY Murine Hepatitis Virus (MHV) Respiratory, Enteric, Hepatic, and
Neurologic Infections in Mice
• Enveloped, non-segmented, positive-sense RNA viruses, are
characterized by club-like spikes that project from their
surface (defining feature of the virion, and give them the HUMAN CORONAVIRUS
appearance of a solar corona, prompting the name,
coronaviruses) VIRUS LOCATION ANIMAL HOST
• Coronaviruses are the largest group of viruses belonging to SARS-CoV Guandong Province Origin:
the Nidovirales order, which includes Coronaviridae, (2002-2003) China Bats
Arteriviridae, Mesoniviridae, and Roniviridae families. Intermediate Host:
• Some cause disease in animals (e.g. entetritis in cows, and Masked Palm Civet
pigs, or URT in chickens) MERS-CoV Saudi Arabia and other Origin:
• Severe acute respiratory syndrome (SARS), and Middle East (2012) countries in Middle East Bats
respiratory syndrome (MERS) are also caused by Intermediate Host:
coronaviruses that “jumped” from animals to humans. Dromedary Camels

CORONAVIRUS LIFE CYCLE

Check appendix for diagram of life cycle
• Attachment and Entry
− Interaction of virus S protein with host receptor
− Host Receptors
§ SARS-CoV – Angiotensin Converting Enzyme 2
Receptor
§ MERS-CoV – Dipeptidyl Dipepetidase 4
− Fusion with acidified endosomes, or plasma membrane
− Release of viral genome into cytoplasm
• Replicase Protein Expression
− Translation (mRNA to protein synthesis) of replicase
gene from virion genomic RNA
• Replication, and Transcription
− Perhaps the most novel aspect of coronavirus
replication is how the leader and body transcription
regulatory segments (TRS) fuse during production of
sub-genomic RNAs
− Coronaviruses are also known for their ability to
recombine using both homologous and
nonhomologous recombination
• Assembly and Release
− The viral structural proteins, S, E, and M are translated
and inserted into the endoplasmic reticulum (ER)
− These proteins move along the secretory pathway into
the endoplasmic reticulum–Golgi intermediate VIROLOGY OF SARS-CoV-2
compartment (ERGIC) • SARS-CoV-2 is a group 2b beta-coronavirus that has at least
− Viral genomes encapsidated by N protein bud into 70% similarity in genetic sequence to SARS-CoV
membranes of the ERGIC containing viral structural • SARS-CoV-2 originated in bats (A certain journal had
proteins, forming mature virions something additionally interesting to say about this)
• SARS-CoV-2 may have pangolins as intermediate host
FUN FACTS ON ANIMAL CORONAVIRUSES • SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2)
receptor for attachment
ANIMAL CORONAVIRUS DISEASES • SARS-CoV-2 does not use other coronavirus receptors such
Transmissible Gastroenteritis Severe Gastroenteritis in Young as aminopeptidase N, and dipeptidyl peptidase 4
Virus (TGEV) & Piglets
• Four essential structural proteins of SARS-CoV-2:
Porcine Epidemic Diarrhea Virus
(PEDV)
− Spike (S) glycoprotein
Porcine Hemagglutinating Encephalitis, Vomiting, and − Small envelope (E) protein
Encephalomyelitis Virus (PHEV) Wasting in Pigs − Matrix (M) protein
Feline Enteric Coronavirus Mild or Asymptomatic Infection − Nucleocapsid (N) protein,
(FCOV) on Domestic Cats

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 2

ACE2 RECEPTOR • Ten genome sequences of 2019-nCoV obtained from the
• 83% of ACE2-expressing cells were alveolar epithelial type II nine patients were extremely similar, exhibiting more than
cells (AECII) 99.98% sequence identity.
• Also found in many extrapulmonary tissues including heart, • Phylogenetic analysis revealed that 2019-nCoV fell within
kidney, endothelium, and intestine the subgenus Sarbecovirus of the genus Betacoronavirus,
− Highly expressed on the luminal surface of intestinal • Genetically distinct from SARS-CoV
epithelial cells (a co-receptor for nutrient uptake • Homology modelling revealed that 2019-nCoV had a similar
particularly for amino acid resorption from food) receptor-binding domain structure to that of SARS-CoV,
− The intestine might also be a major entry site for SARS- despite amino acid variation at some key residues.
CoV-2, and that the infection might have been initiated • These data are consistent with a bat reservoir for
by eating food from the Wuhan market, the putative coronaviruses in general and for 2019-nCoV in particular.
site of the outbreak. • However, despite the importance of bats, several facts
suggest that another animal (maybe Pangolins) is acting as
an intermediate host between bats and humans.
1. First, the outbreak was first reported in late December,
2019, when most bat species in Wuhan are hibernating.
2. Second, no bats were sold or found at the Huanan
seafood market, whereas various non-aquatic animals
(including mammals) were available for purchase.
3. Third, the sequence identity between 2019-nCoV and its
close relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21
was less than 90%, which is reflected in the relatively
long branch between them.Hence, bat-SL-CoVZC45
and bat-SL-CoVZXC21 are not direct ancestors of 2019-
nCoV.
4. Fourth, in both SARS-CoV and MERS-CoV, bats acted as
the natural reservoir, with another animal (masked palm
civet for SARS-CoV and dromedary camels for MERS-
CoV) acting as an intermediate host, with humans as
terminal hosts.
− Therefore, on the basis of current data, it seems likely
that the 2019-nCoV causing the Wuhan outbreak might
also be initially hosted by bats, and might have been
transmitted to humans via currently unknown wild
animal(s) sold at the Huanan seafood market.

III. EPIDEMIOLOGY
GLOBAL
You may access https://covid19.who.int for daily updates

WORLD HEALTH ORGANIZATION AS OF APRIL 24, 2020

• Confirmed Cases: 2,626,321
• Confirmed Deaths: 181,938

CHINA
• Mostly involved older individuals (≥60 years) and persons
with serious underlying health conditions.
• Many initial cases associated with direct exposure to live
markets, while subsequent cases were not
• Incubation time for new infections was found to be 5.2 days,
with a range of 4.1-7 days (Longest time from infection to
symptoms seemed to be 12.5 days)
• March 10, 2020 - Dr. Zunyou Wu of the CCDC
− Mean time from exposure to symptoms - 5-6 days.
GENOMIC CHARACTERISATION AND EPIDEMIOLOGY OF Patients with mild cases - recover within 2 weeks
2019 NOVEL CORONAVIRUS: IMPLICATIONS FOR VIRUS − Patients with severe infections - 3-6 weeks to recover.
ORIGINS AND RECEPTOR BINDING BY LU ET AL., THE LANCET − Deaths - 2-8 weeks following symptom onset
(FEBRUARY 22, 2020) − Patients can shed virus 1-2 days before symptoms
• Next-generation sequencing of samples from appear,
bronchoalveolar lavage fluid, and cultured isolates from • Initial report of 41 patients by Huang et al
nine inpatients, eight of whom had visited the Huanan − 78% male predominance
seafood market in Wuhan. − 32% with underlying disease

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 3

 CHILDREN IV. PATHOPHYSIOLOGY
• 149,082 laboratory-confirmed COVID-19 cases bet. February
12 and April 2, 2020, in the United States
− 1.7% involved children (< 18 years) TRANSMISSION
− 73% had fever, cough, or shortness of breath • Via respiratory droplets from coughing, and sneezing
− 20% were hospitalized • Virus released in respiratory secretions can infect other
− Hospitalizations: <1 yr > older child > younger child individuals via direct contact with mucous membranes.
• Dong et al on 2,143 children younger than 18 years infected • Droplets usually cannot travel more than 6 feet.
in Wuhan, China, between January 16 and February 8, 2020 • Reproduction number (R0 - R naught) = 2.2
− The median age was 7 years − Estimated that an infected individual is likely to spread
− 56.6% were male the disease to an average of 2.2 people
− <10% were severe or critical cases (younger age
yespecially infancy increased the risk of severe illness) INCUBATION PERIOD
• Symptoms develop 2 days to 2 weeks following exposure to
PREGNANT WOMEN AND NEONATES the virus
• Outcomes of 10 neonates born to mothers with confirmed • In a study, mean incubation period was 5.1 days and that
COVID-19 (Zhu et al) 97.5% of individuals who developed symptoms did so within
− 4 were symptomatic prior to delivery 11.5 days of infection.
− 2 became symptomatic at delivery
− 3 developed symptoms in the postpartum period
− 9/10 neonates negative for COVID-19 from 1-9 days
RISK FACTORS
• Include (but are not limited to):
following delivery (one mother died).
− Advanced age
− Infants most commonly experienced respiratory distress
− Immunocompromised state
− Abnormal liver function and thrombocytopenia aware
− Diabetes
also observed
− Cardiovascular disease
− 6 premature birth
− Hypertension
• 33 neonates born to mothers with COVID-19 (Zeng et al.) − Chronic pulmonary disease
− CS delivery w/ good outcomes overall, and use of − Chronic renal disease
infection control precautions − Liver disease
− 3 with early-onset pneumonia but eventually recovered − Malignancy
• 9 pregnant women with COVID-19 with live births delivered − Severe obesity
via cesarean delivery in Wuhan, China (Chen et al.) • Occupational Risk
− 7/9 with fever, 4/9 with cough, 3/9 with myalgia, 2/9 with − Employees of seafood and wet animal wholesale
sore throat, and 2/9 with malaise markets in Wuhan
− 5/9 lymphopenia (< 1.0 × 109 cells/L) − Healthcare workers
− 3/9 increased aminotransferase concentrations − Frontliners
− 2/9 neonates reported to have fetal distress.

PHILIPPINES PATHOPHYSIOLOGY OF COVID-19

Note: Read pathophysiology on Pneumonia, and ARDS to understand
You may access https://www.doh.gov.ph/covid19tracker or
how the symptoms of COVID-19 will develop as the host immune system
http://www.covid19.gov.ph to have updates on Philippine statistics daily
responds to the entry of the virus, and destruction of host cells.

DOH COVID-19 TRACKER AS OF APRIL 24, 2020 STAGE 1: ASYMPTOMATIC STATE (INITIAL 1–2 DAYS OF
• Total Confirmed Cases: 7,192 INFECTION)
• Currently Admitted: 5,953
• The inhaled virus SARS-CoV-2 likely binds its spike (S) protein
• Deaths: 477
to angiotensin-converting enzyme 2 (ACE2) receptor of the
• Recovered: 762
epithelial cells in the nasal cavity
• Local replication, and propagation of the virus
TESTING
1. After the virus enters the cells, the viral RNA genome is
• Grand Total of Individuals Tested: 68,765 released into the cytoplasm
2. Viral genome is translated into two polyproteins, and
ILOILO structural proteins
Added Iloilo to my personal notes because I’m stranded here 3. The viral genome begins to replicate
4. The newly formed envelope glycoproteins are inserted
DOH COVID-19 TRACKER AS OF APRIL 22, 2020 into the membrane of the endoplasmic reticulum or
• Western Visayas Medical Center (WVMC) Individuals Tested: Golgi, and the nucleocapsid is formed by the
2,485 combination of genomic RNA, and nucleocapsid
• Total Confirmed in Iloilo: 25 protein.
• Currently Admitted: 16 5. Then, viral particles germinate into the endoplasmic
• Deaths: 5 reticulum-Golgi intermediate compartment (ERGIC).
• Recovered: 4 6. Lastly, the vesicles containing the virus particles then
fuse with the plasma membrane to release the virus
• Limited innate immune response.
• At this stage the virus can be detected by nasal swabs.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 4

STAGE 2: UPPER AIRWAY AND CONDUCTING AIRWAY • Normal flora adhering to mucosal cells of the oropharynx -
RESPONSE (NEXT FEW DAYS) prevents pathogenic bacteria from binding
• The virus propagates and migrates down the respiratory • Alveolar macrophages - are extremely efficient at clearing
tract along the conducting airways and killing pathogens. Macrophages are assisted by
• More robust innate immune response is triggered • Proteins (e.g., surfactant proteins A and D) - have
• Nasal swabs or sputum should yield the virus (SARS-CoV-2) intrinsic opsonizing properties or antibacterial or antiviral
• Disease is clinically manifested activity.
• 80% of patients will present with a mild disease
Only when the capacity of the alveolar macrophages to ingest
STAGE 3: HYPOXIA, GROUND GLASS INFILTRATES, AND or kill the microorganisms is exceeded does clinical pneumonia
become manifest. The host inflammatory response, rather than
PROGRESSION TO ARDS
proliferation of microorganisms, triggers the clinical syndrome of
• About 20% of the infected patients will progress to stage 3 pneumonia
disease and develop pulmonary infiltrates
• The virus now reaches the gas exchange units of the lung INFLAMMATORY RESPONSE
and infects alveolar type II cells
• Alveolar macrophages initiate the inflammatory response to
• SARS-CoV propagates within type II cells
bolster lower respiratory tract defenses.
• Large number of viral particles are released
• Cells undergo apoptosis and die SIGNS & SYMPTOMS CAUSED BY
• Released viral particles infect adjacent type II pneumocytes Fever Interleukin 1 and Tumor Necrosis
• Damaged cells induce innate inflammation in the lungs that Factor
is largely mediated by pro-inflammatory macrophages and Peripheral Leukocytosis and Chemokines like Interleukin 8 and
granulocytes. increased purulent secretions Granulocyte Colony-Stimulating
• Lung inflammation is the main cause of life-threatening Factor
respiratory disorders at the severe stage Release of neutrophils and their
attraction to the lung
Radiographic infiltrate on X-ray Inflammatory mediators cause
Rales detectable on elveolar capillary leak (Even
auscultation erythrocytes can cross the
Hypoxemia results from alveolar alveolar-capillary membrane, with
filling consequent hemoptysis)
Respiratory Alkalosis The capillary leak results in a
Increased respiratory drive
Dyspnea. Decreased compliance due to
capillary leak
Hypoxemia
Increased respiratory drive,
increased secretions
Occasional infection-related
bronchospasm

• In some cases, there is a 'cytokine storm'

− Extensive tissue damage
− Mediated by interleukin 6 (IL-6)

PATHOLOGIC CHANGES
PATHOPHYSIOLOGY OF PNEUMONIA
• Pneumonia results from the proliferation of microbial FIRST PHASE: EDEMA
pathogens at the alveolar level, and the host’s response to − Presence of a proteinaceous exudate in the alveoli
those pathogens. − Bacteria in the alveoli

WAYS MICROORGANISMS CAN GAIN ACCESS TO THE SECOND PHASE: RED HEPATIZATION
LOWER RESPIRATORY TRACT − Presence of erythrocytes in the cellular intraalveolar
• The most common is by aspiration from the oropharynx. exudate
• Many pathogens are inhaled as contaminated droplets. − Neutrophil influx
• Rarely, pneumonia occurs via hematogenous spread (e.g., − Bacteria are occasionally seen
from tricuspid endocarditis)
• Contiguous extension from an infected pleural or THIRD PHASE: GRAY HEPATIZATION
mediastinal space.
− No new erythrocytes are extravasating
HOST DEFENSE − Those already present have been lysed and degraded
• Hairs and turbinates of the nares - Capture larger inhaled − The neutrophil is the predominant cell
particles before they reach the lower respiratory tract. − Fibrin deposition is abundant
• Mucociliary clearance and local antibacterial factors in − Bacteria have disappeared
tracheobronchial tree − Corresponds with successful containment of the
• Gag reflex and Cough mechanism - protection from infection and improvement in gas exchange
aspiration.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 5

FOURTH PHASE: RESOLUTION • Most patients recover rapidly and are liberated from
− Macrophage reappears as the dominant cell type mechanical ventilation during this phase.
− Debris of neutrophils, bacteria, and fibrin has • Dyspnea, tachypnea, and hypoxemia
− been cleared • Progressive lung injury and early changes of pulmonary
fibrosis
Lymphocyte-predominant pulmonary infiltrate.
PATHOPHYSIOLOGY OF ACUTE •
• Type II pneumocytes proliferate along alveolar basement
RESPIRATORY DISTRESS SYNDROME membranes, synthesize new pulmonary surfactant, and
differentiate into type I pneumocytes.
CLINICAL DISORDERS COMMONLY ASSOCIATED
FIBROTIC PHASE
WITH ARDS • Some recover lung function 3–4 weeks after
DIRECT LUNG INJURY INDIRECT LUNG INJURY
• Some enter a fibrotic phase that may require long-term
Pneumonia Sepsis support on mechanical ventilators and/or supplemental
Aspiration of gastric contents Severe trauma oxygen.
Pulmonary contusion Multiple bone fractures • Marked disruption of acinar architecture leads to
Near-drowning Flail chest emphysema-like changes, with large bullae.
Toxic inhalation injur y Head trauma • Intimal fibroproliferation in the pulmonary microcirculation
Burns causes progressive vascular occlusion and pulmonary
Multiple transfusions
hypertension.
Drug overdose
Pancreatitis
• Physiologic Consequences include
Postcardiopulmonary bypass − Increased risk of pneumothorax
− Reductions in lung compliance
DIAGNOSTIC CRITERIA − Increased pulmonary dead space.
TA
Severity: Oxygenation Mild
200 mmHg < PaO2/FiO2 ≤ 300 mmHg
V. CLINICAL MANIFESTATIONS
Check appendix for course of illness
Moderate
100 mmHg < PaO2/FiO2 ≤ 200 mmHg
Severe APPROACH TO A PATIENT
PaO2/FiO2 ≤ 100 mmHg • Physical examination should be done in a enclosed area
Onset Acute • An airborne infection isolation room is ideal
Chest Radiograph Bilateral alveolar or interstitial infiltrates
• Patients should wear surgical mask
Absence of Left Atrial Pcwp ≤18 mmhg or no clinical evidence of
Hypertension increased left atrial pressure
• Standard contact and airborne precautions should be
BLE 322-2 observed, and treating healthcare personnel should wear
eye protection
CLINICAL COURSE AND PATHOPHYSIOLOGY
EXUDATIVE PHASE PERTINENT HISTORY
• Time: First 7 days of illness after exposure to a precipitating • Travel history to an area with active local transmission within
ARDS risk factors. 14 days
• Alveolar capillary endothelial cells & type I pneumocytes • Exposure to an individual who recently returned from a
(alveolar epithelial cells) are injured country or area experiencing active local transmission
• Loss of the normally tight alveolar barrier (Example: from Wuhan City, China) within 14 days
• Edema fluid that is rich in protein accumulates • Exposure to an individual under investigation (with signs and
− Cytokines (e.g., interleukin 1, interleukin 8, and tumor symptoms, or travel history) within 14 days
necrosis factor α), and lipid mediators (e.g., leukotriene • Exposure to an individual with laboratory-confirmed COVID-
B4 ) 19 within 14 days
− Condensed plasma proteins aggregate to form hyaline • A complete or partial loss of the sense of smell (anosmia)
membrane whorls has been reported as a potential history finding in patients
− Involves dependent portions of the lung, with diminished eventually diagnosed with COVID-19
aeration, and atelectasis.
• Leukocytes (especially neutrophils) traffic into the SIGNS & SYMPTOMS
pulmonary interstitium and alveoli. • Ranges from asymptomatic/mild symptoms to severe illness
• Pulmonary vascular injury and mortality
• Collapse of sections of lung = Decreased lung compliance • Fever
• Intrapulmonary shunting and hypoxemia develop and the • Cough
work of breathing increases, leading to dyspnea (rapid • Shortness of breath
shallow breathing and an inability to get enough air) • Malaise
• Hypercapnia secondary to an increase in pulmonary dead • Myallgia
space is prominent in early ARDS. • Fatigue
• Tachypnea • Respiratory distress/ Dyspnea

PROLIFERATIVE PHASE
• Time: Day 7 to day 21.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 6

Table 1. Clinical signs and symptoms of patient with COVID19 infections
SYMPTOM/SIGNS Huang et al. Chen et al. Wang et al.
Fever 98% 83% 98.6%
Cough 76% 82% 82% (Dry Cough)
Shortness of breath 55% 31% 31.2%
Muscle ache 44% 11% 34.8%
Confusion NR 9% NR
Headache 8% 8% 6.5%
Sore throat NR 5% 17.4%
Rhinorrhea NR 4% NR
Chest pain NR 2% NR
Diarrhea 3% 2% 10.1%
Nausea and NR 1% 10.1% (Nausea)
Vomiting 3.6% (Vomiting)
Fatigue NR NR 69.6%

PATIENT CATEGORIZATION
• Administrative Order No. 2020-0013 on April 9, 2020 – New
categorization of patients

SUSPECT
• A patient will be classified as "suspect" if they fall under any
of the three:
1. Patient has the following symptoms:
− Fever of at least 38 degrees C
− Cough
− Throat Pain LABORATORY EXAMS
− And either of the two:
§ Has travel history or lives in community with local
COVID-19 transmission within 14 days since start of
POLYMERASE CHAIN REACRION (PCR)
symptoms • Real-time reverse transcription–polymerase chain reaction
§ Had close contact with a confirmed or probable (rRT-PCR) assay
COVID-19 case within 14 days since start of
symptoms SAMPLE TO BE USED
2. Patient has the following symptoms: • Nasopharyngeal swabs (NPS) AND Oropharyngeal swabs
− Fever (OPS)
− Cough • Sputum, endotracheal aspirate, or bronchoalveolar lavage
− Difficulty of Breathing fluid as appropriate. Clinicians may elect to collect only LRT
− And is any of the following: samples when these are readily available (for example, in
§ 60 years old and above mechanically ventilated patients).
§ Has preexisting condition • A Chinese study reported that positive rates varied by
§ Has sensitive pregnancy sample type tested
§ A health worker − Specimen types with the highest rates of positive results
3. Patient experiences sudden onset of lung illness with severe included:
symptoms of unknown origin and needs hospitalization § BAL fluid (14/15; 93%)
§ Sputum (75/104; 72%)
§ Nasal swabs (5/8; 63%)
PROBABLE
§ Brush biopsy (6/13; 46%)
• A person will be classified as "probable" if he/she was earlier § Pharyngeal swabs (126/398; 32%)
tagged as a "suspect" and has the following: § Feces (44/153; 29%)
− Still undetermined COVID-19 results § Blood (3/307; 1%)
− Test was not done in an official laboratory with RT-PCR § Urine (0/72; 0%)
test (reverse transcription polymerase chain reaction, • Nasal swabs were found to contain the most virus.
considered the “gold standard” in COVID-19 testing) • Upper respiratory tract specimens have been reported to
− Remains untested contain a smaller viral load than lower respiratory tract
specimens do.
CONFIRMED • If PCR tests are negative for SARS-CoV-2 using upper
• A person will be considered a confirmed COVID-19 case if respiratory tract specimens despite persistent clinical
RT-PCR testing shows positive result for coronavirus. suspicion, the WHO recommends retesting using lower
respiratory tract specimens.

MATERIALS FOR SAMPLE COLLECTION

• Healthcare workers should wear the following PPE
− Eye protection
− Surgical mask
− Double gloves

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 7

 − Disposable impermeable, breathable, long-sleeved, COLLECTION OF LOWER RESPIRATORY SPECIMENS
laboratory gown fastened at the back • Lower respiratory tract specimens should be collected in
− If the specimen is collected with an aerosol-generating sterile containers.
procedure, staff should wear a particulate respirator at • Avoid sputum induction to reduce the risk of aerosol
least as protective as a NIOSH-certified N95, an EU transmission.
standard FFP2, or the equivalent
• Procedure for collecting respiratory specimens SPECIMEN HANDLING
− Use sterile Dacron or rayon viral swabs for collecting
• Place swabs immediately into a sterile vial containing 2 ml
upper respiratory tract specimens from both the
of viral transport media without antibiotics
nasopharynx and the oropharynx.
− Both swabs can be placed in the same vial, if desired.
− Do not use calcium alginate swabs
− Aseptically, cut or break applicator sticks off near the
tip to permit tightening of the cap.
COLLECTING THE OROPHARYNGEAL SWABS
• Label the vial with the patient’s name, specimen type, date
1. Insert swab into the posterior pharynx and tonsillar areas. collected and other required information.
2. Rub swab over both tonsillar pillars and posterior • If specimens will be examined within 48 hours after
oropharynx and avoid touching the tongue, teeth, and collection, keep specimen at 4*C and ship on wet ice or
gums. refrigerant gel-packs, otherwise store frozen at ≤ 70*C and
3. Do not sample the tonsils. ship on dry ice.
• Avoid freezing and thawing specimens.
• Specimens should be packaged using the triple packaging
system detailed below
− Primary Receptacle: Seal using Parafilm and rrap the
primary receptacle with an absorbent material e.g.,
gauze.
− Secondary Container: The second container should
be durable and leak-proof.
− Outer Container: E.g., ice box. Ensure that the required
temperature is maintained in the outer container
through the use of wet ice or refrigerant packs.

COLLECTING THE NASOPHARYNGEAL SWABS

1. Insert flexible wire shaft swab through the nares parallel to
the palate (not upwards) until resistance is encountered or
the distance is equivalent to that from the ear to the nostril
of the patient indicating contact with the nasopharnyx
2. Gently, rub and roll the swab.
3. Leave the swab in place for several seconds to absorb
secretions before removing.
4. Do not sample the nostrils.

CITE OF TESTING
• All specimens for nCoV testing should be sent to the
Research Institute for Tropical Medicine (RITM) by the health
facility (Guideline as of Feb 2020)
• Certified Subnational Testing Centers
− UP National Institutes of Health and San Lazaro Hospital
in Manila
− Philippine Red Cross and Detoxicare Molecular
Diagnostics Laboratory in Mandaluyong
− Lung Center of the Philippines, St. Luke’s Medical
Center, and Victoriano Luna Hospital in Quezon City
− The Medical City in Pasig
− Makati Medical Center; St. Luke’s Medical Center-BGC
in Taguig
− Research Institute for Tropical Medicine, Inc. in
Muntinlupa
− Baguio General Hospital and Medical Center
− Vicente Sotto Memorial Medical Center in Cebu
− Southern Philippines Medical Center in Davao
− Western Visayas Medical Center in Iloilo

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 8

 − Bicol Regional Diagnostic and Reference Laboratory in − Peripheral distribution (80%)
Legazpi City − Ground-glass opacity (91%)
− Fine reticular opacity (56%)
X-RAY − Vascular thickening (59%)
• Consolidation (commonly bilateral and of lower zone • (American College of Radiology) Recommends against
distribution) using CT scanning for screening or diagnosis but instead
• Ground-glass opacities reserving it for hospitalized patients.
• Pulmonary infiltrates • May have findings in apparently asymptomatic individuals.
• Pleural effusion was an uncommon finding.
• Severity on chest radiography peaked 10-12 days following Progression of CT Abnormalities (Mingzhi et al)
onset. 1. Early phase (0-4 Days)
− Multiple small patchy shadows and interstitial changes
begin to emerge in a distribution beginning near the
pleura or bronchi rather than the pulmonary
parenchyma.
− Subpleural ground glass opacities (GGO) located in the
lower lung lobes
2. Progressive phase (5-8 Days)
− The lesions enlarge and increase, evolving to multiple
ground-glass opacities and infiltrating consolidation in
both lungs.
− Bilateral distribution of the infective process and diffuse
GGO.
3. Severe phase (9-13 Days)
− Massive pulmonary consolidations occur, while pleural
effusion is rare.
− Dense consolidation, crazy-paving pattern and residual
parenchymal bands
4. Dissipative phase (>14 Days)
− Ground-glass opacities and pulmonary consolidations
are absorbed completely. The lesions begin evolving
into fibrosis

CT SCAN
• Ground-glass opacities, possibly with consolidation
• Usually bilateral, involve the lower lobes, and have a
peripheral distribution
• Pleural effusion, pleural thickening, and lymphadenopathy
have also been reported, but with less frequency
• Study by Bai et al.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 9

 VIRAL CULTURE
• Virus isolation in cell culture or initial characterization of viral
agents recovered in cultures of specimens is not
recommended for biosafety reasons

COMPLETE BLOOD COUNT

• Leukopenia, or Leukocytosis
• Neutrophilia
• Lymphopenia
• Decreased Hemoglobin
• Decreased Platelets

BLOOD CHEMISTRY
• Elevated Alanine Aminotransferase (ALT)
• Elevated Aspartate Aminotransferase (AST)
• Elevated C-reactive protein
• Elevated Creatine Kinase
• Elevated Blood Urea Nitrogen
• Elevated Serum Creatinine levels.
• Elevated Lactate dehydrogenase
• Elevated Ferritin levels
• Elevated CRP levels
• Elevated Procalcitonin

COAGULATION TESTS
• Prolonged Prothrombin time
• Elevated D-Dimer

VI. MANAGEMENT
Mainly taken from PSMID, RITM and DOH Guidelines as of
February 11, 2020

MATERIALS NEEDED
• PPE
• Disposable or dedicated equipment including a
thermometer, stethoscope and blood pressure apparatus
• Pulse oximeters
• Functioning oxygen systems
• Disposable, single-use, oxygen-delivering interfaces (nasal
cannula, simple face mask, and mask with reservoir bag)
• Use standard, contact, droplet/airborne precautions when
handling contaminated oxygen interfaces of patients with
COVID infection
ANTIBODY TESTING
A qualitative immunoglobulin M (IgM)/immunoglobulin G
APPROACH CONSIDERATIONS
•
(IgG) antibody test for SARS-CoV-2 using serum, plasma
(EDTA or citrate), or venipuncture whole blood. • No specific antiviral treatment is recommended for COVID-
• IgM antibodies - Detectable days after initial infection 19
• IgG antibodies - Detected later. • Infected patients should receive supportive care to help
• Study by Wu F et al alleviate symptoms.
− Higher levels of antibody correlated with older and • No vaccine is currently available for SARS-CoV-2.
middle age and higher CRP levels at admission but • Avoidance is the principal method of deterrence
negatively correlated with lymphocyte count at
admission CLASSIFICATION OF ADULT PATIENTS
− The authors raised concerns about the development of A. Patients with uncomplicated upper respiratory tract
lasting immunity after infection infection
• Study by Guo et al B. Patients with mild pneumonia
− IgM enzyme-linked immunoassay (ELISA) results were C. Patients with severe pneumonia, severe sepsis or septic
positive in 93% of patients with suspected COVID-19 shock
(characteristic radiographic, clinical, and D. Patients with Acute Respiratory Distress Syndrome (ARDS)
epidemiologic features) despite negative PCR results
and despite negative results on plasma specimens
tested before the COVID-19 outbreak

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 10

 GROUP A: PATIENTS WITH UNCOMPLICATED SIGNS AND SYMPTOMS
UPPER RESPIRATORY TRACT INFECTION • Septic Shock: Persisting hypotension despite volume
resuscitation, requiring vasopressors to maintain MAP ≥65
mmHg, and serum lactate level >2 mmol/L
SIGNS AND SYMPTOMS
• Non-specific symptoms such as fever, cough, sore throat, MANAGEMENT
nasal congestion, headache, muscle pain or malaise.
• Manage as CAP-High Risk based on 2020 Philippine CAP
Guidelines
MANAGEMENT
Admit to a designated isolation room
•
• Give symptomatic treatment and supportive care as
GROUP D: PATIENTS WITH ACUTE RESPIRATORY
needed DISTRESS SYNDROME (ARDS)
• Most cases will not require antibiotic treatment.
SIGNS AND SYMPTOMS
GROUP B: PATIENTS WITH MILD PNEUMONIA • New or worsening respiratory symptoms (e.g. SpO2 < 90%,
RR> 30 breaths/minute, with or without progressing infiltrates
SIGNS AND SYMPTOMS on CXR) within one week of known clinical insult
• With mild pneumonia (e.g. RR <30, HR <125, SpO2 >90% on
room air) MANAGEMENT
• Consider ARDS
MANAGEMENT • Management will depend on classification of ARDS.
• Manage as CAP-Low Risk based on 2020 Philippine CAP
Guidelines CLASSIFICATION OF PEDIATRIC PATIENTS
A. Patients with uncomplicated upper respiratory tract
GROUP C: PATIENTS WITH SEVERE PNEUMONIA, infection
B. Patients with mild pneumonia
SIGNS AND SYMPTOMS C. Patients with severe pneumonia, severe sepsis or septic
• Fever or suspected respiratory infection, plus one of the shock
following: D. Patients with Acute Respiratory Distress Syndrome (ARDS)
− Respiratory rate >30 breaths/min
− Severe respiratory distress, or SpO2 <90% on room air GROUP A: PATIENTS WITH UNCOMPLICATED
UPPER RESPIRATORY TRACT INFECTION
MANAGEMENT
• Manage as CAP-Moderate Risk based on 2020 Philippine SIGNS AND SYMPTOMS
CAP Guidelines
• Non-specific symptoms such as fever, cough, sore throat,
nasal congestion, headache, muscle pain or malaise.
GROUP C: PATIENTS WITH SEVERE SEPSIS
MANAGEMENT
SIGNS AND SYMPTOMS • Admit to a designated isolation room
• Sepsis: life-threatening organ dysfunction caused by a • Give symptomatic treatment and supportive care as
dysregulated host response to suspected or proven needed
infection, presenting as follows: • Most cases will not require antibiotic treatment.
− Altered mental status
− Difficult or fast breathing (RR>30 breaths/minute) GROUP B: PATIENTS WITH MILD PNEUMONIA
− Low oxygen saturation (< 90% on room air) or arterial
hypoxemia (PaO2/FiO2 < 300)
SIGNS AND SYMPTOMS
− Reduced urine output (U/O <0.5 mL/kg/hour for at least
• Child with non-severe pneumonia has:
2 hours despite adequate fluid resuscitation)
− Cough or Difficulty breathing
− Fast heart rate (>90 beats/minute), weak pulse, cold
− Fast breathing (in breaths/min):
extremities or low blood pressure (Systolic NP <90
§ <2 months - ≥60
mmHg, mean arterial pressure (MAP) < 70 mmHg)
§ 2–11 months - ≥50
− Skin mottling, or
§ 1–5 years - ≥40
− Laboratory evidence of coagulopathy (INR >1.5 or aptt
− No signs of severe pneumonia
> 60 seconds), thrombocytopenia (platelet count <
100,000/um), acidosis, high lactate (>2 mmol/L) or
MANAGEMENT
hyperbilirubinemia (>4 mg/dL)
• Admit to a designated isolation room
MANAGEMENT • Manage as pediatric community-acquired pneumonia
(pCAP) A/ B
• Manage as CAP-High Risk based on 2020 Philippine CAP
Guidelines
GROUP C: PATIENTS WITH SEVERE PNEUMONIA,
GROUP C: PATIENTS WITH SEPTIC SHOCK
SIGNS AND SYMPTOMS

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 11

• Child with cough or difficulty in breathing, plus at least one • Management will depend on classification of ARDS
of the following:
− Central cyanosis or SpO2 <90% PNEUMONIA
− Severe respiratory distress (e.g. grunting, very severe
chest indrawing) OXYGEN THERAPY
− Signs of pneumonia with a general danger sign:
• Give supplemental oxygen therapy immediately to patients
§ Inability to breastfeed or drink
with pneumonia and respiratory distress, hypoxemia, or
§ Lethargy
shock.
§ Unconsciousness
• Initiate oxygen therapy at 5 L/min and titrate flow rates to
§ Convulsions
reach target SpO2 ≥90% in non-pregnant adults and SpO2
• Other signs of pneumonia may be present
≥92-95 % in pregnant patients
− Chest Indrawing
• Children with emergency signs (obstructed or absent
− Fast breathing (in breaths/min):
breathing, severe respiratory distress, central cyanosis,
§ <2 months - ≥60
shock, coma or convulsions) should receive oxygen therapy
§ 2–11 months - ≥50
during resuscitation to target SpO2 ≥94%; otherwise, the
§ 1–5 years - ≥40
target SpO2 is ≥90%.
• All areas where patients with pneumonia are cared for
MANAGEMENT
should be equipped with pulse oximeters, functioning
• Admit to a designated isolation room oxygen systems and disposable, single-use, oxygen-
• Manage as pediatric community-acquired delivering interfaces (nasal cannula, simple face mask, and
• pneumonia (pCAP) C mask with reservoir bag).

GROUP C: PATIENTS WITH SEVERE SEPSIS INTUBATION AND MECHANICAL VENTILATION

• Assess the need for intubation and mechanical ventilation.
SIGNS AND SYMPTOMS • Endotracheal intubation should be performed by a trained,
• Sepsis: suspected or proven infection and ≥2 SIRS criteria, of and experienced provider using airborne precautions.
which one must be abnormal temperature or white blood
cell count FLUID MANAGEMENT
• Use conservative fluid management in patients with
MANAGEMENT pneumonia when there is no evidence of shock.
• Admit to the designated isolation room • Patients with pneumonia should be treated cautiously with
• Manage as pediatric community-acquired pneumonia intravenous fluids, because aggressive fluid resuscitation
(pCAP) C may worsen oxygenation, especially in settings where there
is limited availability of mechanical ventilation.
GROUP C: PATIENTS WITH SEPTIC SHOCK
PHARMACOTHERAPY
SIGNS AND SYMPTOMS • Give appropriate empiric antimicrobials. Refer to guidelines
• Septic Shock: any hypotension (SBP <5th centile or >2 SD in appendix.
below normal for age) or 2-3 of the following: • Although the patient may be suspected to have COVID-19,
− Altered Mental State administer appropriate empiric antimicrobials within ONE
− Tachycardia Or Bradycardia (Hr <90 Bpm Or >160 Bpm hour of identification of sepsis.
In Infants And Hr <70 Bpm Or >150 Bpm In Children) • Give oseltamivir 75 mg per tab BID for adults and 3mg/kg
− Prolonged Capillary Refill (>2 Sec) Or Warm Vasodilation per dose BID for pediatric patients for 5 to 10 days for
With Bounding Pulses patients who are confirmed to have influenza A or B
− Tachypnea infection.
− Mottled Skin Or Petechial Or Purpuric Rash • Empiric therapy includes oseltamivir 75 mg per tab BID for
− Increased Lactate adults and 3mg/kg per dose BID for pediatric patients for 5
− Oliguria to 10 days for treatment of influenza when there is local
− Hyperthermia Or Hypothermia circulation or other risk factors, including travel history.
• Streamline antimicrobial treatment when microbiologic
exam results become available.
MANAGEMENT
• Do NOT routinely give systemic corticosteroids for treatment
• Admit to the designated isolation room
of viral pneumonia or ARDS outside of clinical trials unless
• Manage as pediatric community-acquired pneumonia
they are indicated for another reason.
(pCAP) D
• Closely monitor patients with pneumonia for signs of clinical
deterioration, such as rapidly progressive respiratory failure
GROUP D: PATIENTS WITH ACUTE RESPIRATORY and sepsis, and apply supportive care interventions
DISTRESS SYNDROME (ARDS) immediately.
• Identify and properly manage other co-morbidities
SIGNS AND SYMPTOMS adequately.
• New or worsening respiratory symptoms within one week of
known clinical insult SEPTIC SHOCK
• Admit the patient to designated isolation room/ICU.
MANAGEMENT

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 12

• Give appropriate antimicrobials within one hour of initial MODERATE ARDS
patient assessment. • 100 mmHg < PaO2/FiO2 ≤200 mmHg
• Blood cultures should ideally be collected prior to • with PEEP ≥5 cmH2O, or non-ventilated
antimicrobial treatment, but this should not
delay administration of antimicrobials
SEVERE ARDS
• Determine if infection was acquired in the community or in
• PaO2/FiO2 ≤ 100 mmHg
the hospital setting and provide appropriate empiric
• with PEEP ≥5 cmH2O, or non-ventilated)
therapy based on clinical presentation
• When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS
(including in non-ventilated patients)
FLUID MANAGEMENT
• In adults, administer at least 30 ml/kg of balanced
crystalloid or normal saline solution within 1 hour if with signs
CLASSIFICATION OF ARDS BASED ON
of sepsis-induced hypoperfusion (i.e. hypotension, or serum OXYGENATION AMONG CHILDREN:
lactate levels of ≥4 mmol/L with or without hypotension) • Bilevel NIV or CPAP ≥5 cmH2O via full face mask: PaO2/FiO2
• In children, give 20 ml/kg as a rapid bolus and up to 40-60 ≤ 300 mmHg or SpO2/FiO2 ≤264
ml/kg in the first 1 hr • Mild ARDS (invasively ventilated)
• Do not use hypotonic crystalloids, starches, or gelatins for − 4 ≤ OI < 8 or
resuscitation. − 5 ≤ OSI < 7.5
• Monitor for volume overload during resuscitation. • Moderate ARDS (invasively ventilated)
• Fluid overload can lead to respiratory failure. − 8 ≤ OI < 16 or
• In patients who remain hypotensive, assessment of fluid − 7.5 ≤ OSI < 12.3
responsiveness is suggested before additional fluids are • Severe ARDS (invasively ventilated):
administered. − OI ≥ 16 or
• If fluid unresponsive, − OSI ≥ 12.3
− Vasopressors may be initiated to target MAP ≥65 mmHg
in adults. A higher MAP of 75 to 85 mmHg is suggested MANAGEMENT OF ARDS
for patients with preexisting hypertension. • Admit the patient to the ICU.
− Use of vasopressors should not be delayed. • Recognize severe hypoxemic respiratory failure when a
− If central venous catheters are not available, patient with respiratory distress is failing standard oxygen
vasopressors can be given through a peripheral IV, but therapy.
use a large vein and closely monitor for signs of • Hypoxemic patients without ARDS may benefit from high
extravasation and local tissue necrosis. flow nasal oxygen (HFNO) therapy or non-invasive
− Central venous pressure (CVP) should not be used to ventilation
assess fluid responsiveness. • As progression into ARDS may happen rapidly, these
• If extravasation occurs, stop infusion. patients should be monitored closely in an ICU setting for
• If signs of poor perfusion and cardiac dysfunction persist clinical deterioration and for assessment on need for
despite achieving MAP target with fluids and vasopressors, escalation to invasive mechanical ventilation with
consider an inotrope such as dobutamine. intubation
• Manage ARDS if present. Referral to the appropriate
ACUTE RESPIRATORY DISTRESS SYNDROME specialists (e.g. Pulmonologist and/or Intensivist) is highly
• Recognize severe hypoxemic respiratory failure when a recommended.
patient with respiratory distress is failing standard oxygen • Endotracheal intubation should be performed by a trained
therapy and experienced provider using airborne precautions.
• Implement lung protection strategy with initial tidal volumes
SIGNS AND SYMPTOMS at 6-8 ml/kg of predicted body weight, provision of
• Onset adequate PEEP for recruitment, while limiting inspiratory
− New or worsening respiratory symptoms within one pressures (plateau pressures) below 30 cmH2O
week of known clinical insult • In patients with moderate or severe ARDS, higher PEEP
• Chest imaging (radiograph, CT scan, or lung ultrasound): instead of lower PEEP is suggested.
− Bilateral opacities, not fully explained by effusions, lobar • ARDS patients who remain hypoxemic despite lung
or lung collapse, or nodules protection strategy should be immediately placed prone
• Origin of edema for no less than 12 hours with the goal of lung recruitment.
− Respiratory failure not fully explained by cardiac failure • Reassessment and the decision to terminate prone
or fluid overload. Need objective assessment (e.g. positioning after 12 hours should be made in consultation
echocardiography) to exclude hydrostatic cause of with a pulmonologist and/or an intensivist.
edema if no risk factor present.
FLUID MANAGEMENT
CLASSIFICATION OF ARDS BASED ON • Use a conservative fluid management strategy for ARDS
patients without tissue hypoperfusion.
OXYGENATION AMONG ADULTS: − This is a strong guideline recommendation
− The main effect is to shorten the duration of ventilation.
MILD ARDS • In patients with moderate-severe ARDS (PaO2/FiO2 <150),
• 200 mmHg < PaO2/FiO2 ≤ 300 mmHg neuromuscular blockade by continuous infusion should not
• with PEEP or CPAP ≥5 cmH2O, or non-ventilated be routinely used.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 13

• Extracorporeal life support (ECLS) should be considered • Ameliorate severe damage to lung tissue caused by
when the above measures are unable to provide adequate cytokine release in patients with serious COVID-19
oxygenation. Consider referral to a center with access to infections.
ECLS. • “Cytokine storm” with release of IL-6, IL-1, IL-12, and IL-18,
• Avoid disconnecting the patient from the ventilator, which along with tumor necrosis factor alpha (TNFα) and other
results in loss of PEEP, de- recruitment, and atelectasis. inflammatory mediators in COVID-19 cases
• Minimize nebulizations as they can also cause de- • Increased pulmonary inflammatory response may result in
recruitment. increased alveolar-capillary gas exchange, making
• Keep the ventilator humidified at all times xygenation difficult in patients with severe illness.
• Use in-line catheters for airway suctioning and clamp
endotracheal tube when disconnection is required (for CORTICOSTEROIDS
example, transfer to a transport ventilator). • Not generally recommended for treatment of COVID-19 or
any viral pneumonia.
INVESTIGATIONAL DRUGS AND • Benefit in septic shock patients - tempering the host immune
response to bacterial toxin release.
BIOLOGICS • Can induce harm through immunosuppressant effects
• No drugs or biologics have been proven to be effective for during the treatment of infection and have failed to provide
the prevention or treatment of COVID-19. a benefit in other viral epidemics, such as respiratory
• Numerous antiviral agents, immunotherapies, and vaccines syncytial virus (RSV) infection, influenza infection, SARS, and
are being investigated and developed as potential MERS
therapies.

“SOLIDARITY” CLINICAL TRIAL

CONVALESCENT PLASMA
• FDA is facilitating access to convalescent plasma, antibody-
• By the World Health Organization rich products that are collected from eligible donors who
• An ambitious global "megatrial" among confirmed COVD-19 have recovered from COVID-19
patient randomized to standard care or one of four active • Convalescent plasma has not yet been shown to be
treatment arms (remdesivir, chloroquine or
effective in COVID-19
hydroxychloroquine, lopinavir/ritonavir, or lopinavir/ritonavir
plus interferon beta-1a)
NITRIC OXIDE
inhaled nitric oxide as a supportive measure for treating
ANTIVIRAL AGENTS •
infection in patients with pulmonary complications
• The cost of iNO is reported as exceeding $100/hour.
REMDESIVIR
• A nucleotide analog prodrug NUMB-ASSOCIATED KINASE (NAK) INHIBITORS
• Was studied in clinical trials for Ebola virus infections but • Mitigate systemic and alveolar inflammation in patients with
showed limited benefit COVID-19 pneumonia by inhibiting essential cytokine
• Inhibit replication of other human coronaviruses including signaling involved in immune-mediated inflammatory
Severe Acute Respiratory Syndrome Coronavirus (SARS- response.
CoV) in 2003, and Middle East Respiratory Syndrome • Reduce viral infection in vitro
Coronavirus (MERS-CoV) in 2012. • ACE2 receptors are a point of cellular entry by COVID-19,
which is then expressed in lung AT2 alveolar epithelial cells
LOPINAVIR/RITONAVIR • A known regulator of endocytosis is the AP2-associated
• A combination of lopinavir/ritonavir plus IFNb treatment protein kinase-1 (AAK1)
improved clinical parameters in marmosets and mice • The ability to disrupt AAK1 may interrupt intracellular entry of
infected with MERS-CoV the virus
• Baricitinib (Olumiant; Eli Lilly Co) - a JAK inhibitor, is also
IMMUNOMODULATORS AND OTHER identified as a NAK inhibitor with a particularly high affinity
for AAK1.
INVESTIGATIONAL THERAPIES
STATINS
HYDROXYCHLOROQUINE AND CHLOROQUINE • HMG-CoA reductase inhibitors - cholesterol-lowering
• Widely used antimalarial drugs that elicit •
Also decrease the inflammatory processes of
immunomodulatory effects, and are therefore also used to atherosclerosis.
treat autoimmune conditions (eg, systemic lupus • Questions have arisen whether statins may be beneficial to
erythematosus, rheumatoid arthritis) reduce inflammation associated with COVID-19
• Inhibitors of heme polymerase
Antiviral activity via alkalinization of the phagolysosome,
•
which inhibits the pH-dependent steps of viral replication
RENIN ANGIOTENSIN SYSTEM BLOCKADE
SARS-CoV-2 is known to utilize angiotensin-converting
• Chloroquine, hydroxychloroquine, and azithromycin each
enzyme 2 (ACE2) receptors for entry into target cells.
carry the warning of QT prolongation and can be
• Data are limited concerning whether to continue or
associated with an increased risk of cardiac death when
discontinue drugs that inhibit the renin-angiotensin-
used in a broader population
aldosterone system (RAAS), namely angiotensin-converting
enzyme inhibitors (ACEIs) and angiotensin receptor
INTERLEUKIN-6 INHIBITORS blockers (ARBs)

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 14

• Concern arose regarding appropriateness of continuation
of ACEIs and ARBs in patients with COVID-19 after early
OPERATIVE MANAGEMENT
• Feb. 29, 2020 - The first double lung transplant was
reports noted an association between disease severity and
successflly performed on a patient in China with irreversible
comorbidities such as hypertension, cardiovascular disease,
bilateral lung damage secondary to COVID-19
and diabetes, which are often treated with ACEIs and ARBs.
− Infected with SARS-CoV-2 on 26th January 2020
The reason for this association remains unclear
− Repeated tests confirmed the resolution and absence
• The speculated mechanism for detrimental effect of ACEIs
of ongoing infection
and ARBs is related to ACE2
− Prolonged endotracheal intubation, ventilation, and
• It was therefore hypothesized that any agent that increases
ECMO therapy were nevertheless required
expression of ACE2 could potentially increase susceptibility
− Operation was performed successfully
to severe COVID-19 by improving viral cellular entry
− Patient requiring postoperative observation and
• ACE2 physiologically also converts angiotensin 2 to
medical therapy to avoid infection or rejection
angiotensin 1-7, which leads to vasodilation and may
protect against lung injury by lowering angiotensin 2
receptor binding VII. PROGNOSIS
• It is therefore uncertain whether an increased expression of • Clinically milder than MERS or SARS in terms of severity and
ACE2 receptors would worsen or mitigate the effects of case fatality rate.
SARS-CoV-2 in human lungs. • Worse in:
− Older adults
RECOMMENDATIONS FOR REPEAT TESTING − With Comorbidities
− Men
REPEAT TESTING AFTER A POSITIVE TEST
CLINICAL PROGRESSION
• Submit NPS/OPS and lower respiratory tract specimens (if
possible) 48 hours from the first positive test. • (Chen et al.)
• If still positive, recollect NPS/OPS and lower respiratory tract • Average interval from symptom onset to hospitalization: 4
specimens (if possible) testing every 48 hours until the days (range, 2-7 days) among symptomatic patients
patient has two (2) consecutive negative test results. • Most developed fever
• Hospitalization: average of 16 days (range, 12-20 days)
before discharge.
REPEAT TESTING AFTER AN INITIAL NEGATIVE TEST • Median duration of fever: 10 days after symptom onset.
• Repeat testing for patients with an initial negative 2019- • Radiological abnormalities on day 7
nCoV test result may be performed ONLY if there is a high • Improved radiologically by day 14.
index for suspicion for infection despite an initial negative • Median duration to negative results on RT-PCT using upper
test result. respiratory tract samples was 11 days
• Such conditions include, but are not limited, to the • Viral clearance was more likely to be delayed in ICU
following: patients.
− Clinical deterioration in the presence of an established • The authors concluded that most cases of COVID-19 are
disease etiology, and with adequate treatment mild.
− A single negative test result, particularly if this is from an
upper respiratory tract specimen, does not exclude COMPLICATIONS
infection. Repeat sampling and testing, preferably of
• Pneumonia
lower respiratory specimen, is strongly recommended in
• Acute Respiratory Distress Syndrome
severe or progressive disease
− (Wu, et al.) Older age, neutrophilia, and elevated
− Consider a possible co-infection
lactate dehydrogenase and D-dimer levels increased
− No other etiology for the patient's signs and symptoms
the risks of ARDS and death.
has been identified despite work-up.
• Cardiac Injury
− Clinical specimen(s) initially sent was/were deemed to −
More likely to be older, to have ARDS, and to
be unsatisfactory or insufficient (delay in transport and
experience higher mortality rates.
processing, only NPS or OPS was sent).
− Increased troponin levels
− Cardiac Arrest
CRITERIA FOR DISCHARGE − Cardiomyopathy
FOR PERSON UNDER INVESTIGATION • Arrhythmia
• After the initial test is negative AND any of the following • Sepsis
conditions are met: • Septic Shock
− There is clinical improvement • Liver Dysfunction
− There is no other indication for admission • Acute Kidney Injury
− An alternative diagnosis is available • Multi-Organ Failure
− The possibility of COVID-19 has been ruled out
VIII. PREVENTION
FOR CONFIRMED COVID-19
• Patients who have clinically recovered (with resolution of
symptoms) may be discharged from the hospital after two
PREVENTION
• No vaccine is currently available for SARS-CoV-2.
consecutive negative tests for nCoV.
• Avoidance is the principal method of deterrence.

COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 15

GENERAL MEASURES CLOSURE OF SCHOOLS AND UNIVERSITIES
Handwashing with soap and water for at least 20 seconds.
•
• Alcohol-based hand sanitizer may be used if soap and
LESSONS TO BE LEARNED
water are unavailable.
ISSUES EVENTS AND CONSEQUENCES
• Individuals should avoid touching their eyes, nose, and Lack of Intimidation of clinicians who initially identified
mouth with unwashed hands. Transparency COVD-19
• Individuals should avoid close contact with sick people. Delay in the release of information pertaining to
• Sick people should stay at home (eg, from work, school). COVID-19 cases
• Coughs and sneezes should be covered with a tissue, Travel Aviation services operatied for over a month
followed by disposal of the tissue in the trash. Restriction following the initial outbreak with minmal health
• Frequently touched objects and surfaces should be cleaned Delay screening at international borders
Citizens travelling from high risk areas were able to
and disinfected regularly.
freely pass through large airports without helath
screening
PREVENTING/MINIMIZING COMMUNITY SPREAD Quarantine Wuhan began quarantine on January 23, nearly a
• All individuals in areas with prevalent COVID-19 should be Delay month from the initial report of the virus
vigilant for potential symptoms of infection and should stay Allowed individuals potentially infected with COVID-
home as much as possible, practicing social distancing 19 to spread the infection both nationally and
internationally
(maintaining a distance of 6 feet from other persons) when
Public Lack of transparency allows rumors, speculation
leaving home is necessary.
Misinformation and misinformation to be spread amongst the
• Persons with an increased risk for infection public
− Individuals who have had close contact with a person Racism, incorrect public precautions, and
with known or suspected COVID-19 unprecedented fear surrounding COVID-19
− International travelers (including travel on a cruise Emergency Public Health Emergency of International Concern
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Development development of vaccine and treatment of COVID-
time of the last exposure and distancing (6 feet) from
19
other persons at all times
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coronaviru

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APPENDIX

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COVID-19 | LAST UPDATED: APRIL 24, 2020 | TRANS BY SHAIRA RAE 18