SARS-CoV-2 Case Study: A Deeper Look into the COVID-19 Pandemic in the

Philippines and Around the World

University of Santo Tomas, Manila, Philippines

For the fulfillment of course requirements (Performance Task 2) for SHS Grade 11 BIO-2; Mr.
Jerome Reuben Atayde

Authors: Santos, Kimberly R.; Ricafort, Jondemarco A.; Bustamante, Emmanuel A.; Geronga,
Abero D.; and Pascua, Maria C.

Case Study *all the information in this case study is as of up to date as April 20, 2020* .

Chapter 1
Introduction

The newly arising pandemic in the year 2020 called COVID-19 is caused by a virus named
SARS-CoV-2 (Fig. 1), commonly known as 2019-nCoV, which is very similar to the 2002 SARS-CoV
(Fig. 2) (Drosten et al., 2003; Ksiazek et al., 2003; Y. Zhou et al., 2020; H. Li et al., 2020 & Din &
Boppana, 2020) that infected 8,096 people and caused 774 deaths with an overall mortality rate of
about 9.6% (Drosten et al., 2003; Y. Zhou et al., 2020; & Ksiazek et al., 2003). Previous research
claims that the zoonotic transmission of SARS-CoV-2 started from bats, specifically the horseshoe
bats of the species Rhinolophus affinis (C. Zhang et al., 2020b; C. Lai et al., 2020; Rothan et al., 2020; &
Shereen et al., 2020). Clusters of cases of nCoV infection (now officially named as SARS-CoV-2) were
reported to be epidemiologically linked to the Huanan Seafood Wholesale Market (Huang et al, 2020;
Y. Chen et al., 2020; Ungaro et al., 2020; & Han et al., 2020) where live animals mixed with illegal
wildlife are traded (Yang et al., 2020). It is still unclear which animal acts as the intermediate host
which brought the bat coronavirus to human hosts but multiple studies suggest the Malayan pangolin
(Manis javanica) is the missing link (C. Zhang et al., 2020b; Lam et al., 2020; Weston & Frieman, 2020;
T. Zhang et al., 2020; Ye et al., 2020; & P. Zhou et al., 2020).
SARS-CoV 2 is classified within the order Nidovirales, family Coronaviridae, genus Betacoronavirus
(D. Wu et al., 2005; M. Wang et al., 2020 & Gorbalenya et al., 2020) (Fig. 3) and is enveloped with a
nonsegmented, single-stranded, and positive-sense RNA genomes (Fung & Liu, 2019; J. Chan et al.,
2020a; Lu et al., 2020; & Kooraki et al., 2020) (Fig. 1). The 2019-nCoV genome ranges from 26 to 32
kilobases in length and is probably the largest viral RNA known (Fehr & Perlman, 2015; G. Li, 2020;
& Han, 2020). It’s composed of an approximately 27,000 to 30,000 nucleotides and four main
structural proteins (Fig. 1): the spike glycoprotein (S), the membrane protein (M), the small envelope
protein (E), and the nucleocapsid protein (N) (Schelle et al., 2005; X. Li et al., 2020 & C. Wu et al.,
2020), but Y. Zhou (2020) claims that there are five main structural proteins namely replicase complex
protein (ORF1a/b) which encodes the non-structural proteins of viral RNA synthesis complex
through proteolytic processing (Y. Zhou et al., 2020).
The spike glycoprotein is a critical virion component where it is able to guide the virus and
utilize angiotensin-converting enzyme 2 (ACE2), a transmembrane receptor on mammalian hosts, to
enter the human cells (Letko et al., 2020; Y. Zhou et al., 2020 & C. Zhang et al., 2020b). The primary
target of the virus are the epithelial cells in the respiratory and gastrointestinal tract (Ahmad et al.,
2020), particularly the ciliated bronchial epithelial cells and type-II pneumocytes in the lungs (Brake et
al., 2020; Weston & Frieman, 2020; Khan et al., 2020 & Bonilla-Aldana et al., 2020), which explains
the severe alveolar damage after infection (H. Li et al., 2020).
ACE2 is a metalloprotease expressed in the cells of the lungs, intestine, liver, heart, vascular
endothelium, testis, and kidney (Hamming et al., 2004; & Weston & Frieman, 2020). It is an important
receptor which the SARS-CoV-2 binds to in order to enter the human cell by direct membrane fusion
between the virus and plasma membrane (H. Wang et al., 2008; Shereen et al., 2020; & X. Li et al.,
2020) (Fig. 1) and the transmembrane serine protease 2 (TMPRSS2), suggested by X. Li et al. (2020).
When the virus has finally been engulfed inside the cell, the RNA genome is released into the
cytoplasm and is translated into structural protein and two polyproteins, pp1a and 1ab, which are then
cleaved into small products by viral proteinases (Shereen et al., 2020; & X. Li et al., 2020). The RNA-
dependent RNA polymerase (RdRP) produces a series of subgenomic mRNAs by discontinuous
transcription (Shereen et al., 2020), which are subsequently assembled along with the viral proteins
such as the spike glycoprotein (S), the membrane protein (M), the small envelope protein (E), and the
nucleocapsid protein (N) (Schelle et al., 2005; Shereen et al., 2020; X. Li et al., 2020 & C. Wu et al.,
2020), into virions in the endoplasmic reticulum-Golgi intermediate compartment (X. Li et al., 2020).
It then proceeds to infect more undamaged cells that have an ACE2 receptor after the viral shedding
via vesicles (Shereen et al., 2020).
Despite several decades of research, there is a lack of a specific vaccine or treatment for human
CoVs but understanding the interaction between the SARS-CoV-2 spike protein and the ACE2
receptor (Martinez, 2020) along with the TMPRSS2 (X. Li et al., 2020) might reveal how this virus
overcame the species barrier between animals and humans.

Figure 1. Coronavirus virion structure.

Fig. 1. Produced by Korsman et al., (2012). Parts of the Coronavirus: the genome RNA is complexed with the (N) nucleocapsid protein to form a helical
cased within the viral membrane; (HE) hemagglutinin-esterase; (S) spike, a critical virion component where it is able to guide the virus; (E) small
membrane envelope; (M) membrane are all transmembrane proteins. **Note: replicase complex protein (ORF1ab) is not labeled.

Figure 2. Comparison between SARS-CoV (2002) and SARS-CoV-2 (2019).

Fig. 2. Produced by Hoffmann et al., (2020). SARS-CoV-2 (2019) uses the SARS-CoV (2002) receptor ACE2 for host cell entry; the spike protein of
SARS-CoV-2 (2019) is primed by TMPRSS2; and antibodies against SARS-CoV (2002) spike may offer some protection against SARS-CoV-2 (2019).
 Figure 3.Taxonomy of selected coronaviruses.
Fig. 3. Produced by Hoffmann et al., (2020). Shown is the full taxonomy of selected coronaviruses in comparison with the taxonomy of humans
(Gorbalenya et al., 2020).

Figure 4. 2019-nCoV genome.

Fig. 4. Produced by X. Li et al., (2020). The 5’-terminal two-thirds of the genome ORF1a/b encodes polyproteins, which form the viral replicase
transcriptase complex. The other ORFs on the one-third of the genome encode four main structural proteins: spike S, spike; E, small membrane envelope;
N, nucleocapsid protein; M, membrane are all transmembrane proteins.

Figure 5. Life cycle of SARS-CoV-2 in host cells

Fig. 5. Produced by Shereen et al., (2020). The life cycle of SARS-CoV-2 begins when S protein binds to the cellular receptor ACE2. After receptor
binding, the S protein facilitates viral envelope fusion with the cell membrane through the endosomal pathway. The viral RNA genome is then released
into the cytoplasm and is translated into two polyproteins, pp1a and 1ab, and structural proteins, after which the viral genome begins to replicate. Viral
structural proteins and genome RNA are subsequently assembled into virions in the endoplasmic reticulum-Golgi intermediate compartment. At last,
the vesicles containing the virus particles then fuse with the plasma membrane to release the virus (Schelle et al., 2005; H. Wang et al., 2008; Shereen et
al., 2020; C. Wu et al., 2020; Martinez, 2020; & X. Li et al., 2020).
 Chapter 2
Causes and Process of Transmission of SARS-CoV-2

The causes of the SARS-CoV-2 virus, including the commonly accepted origin of the virus
and the possible cases of the virus; and the process of transmission of the SARS-CoV-2 virus,
including its zoonotic origin starting from the natural host to the suspected intermediate host and to
the human host, as well as the human-to-human transmission will be discussed throughout this
chapter. The SARS-CoV-2 virus, according to numerous researches including Luk et al. (2019),
Shereen et al. (2020), Fisher & Heymann (2020), and J. Sun et al. (2020), claims that humans may
have transmitted this virus from horseshoe bats of the species Rhinolophus affinis (Fig. 6). Bats act as a
reservoir of viruses but doesn't get sick due to their unique immune system which may have been the
natural reservoir of the 2019-nCoV just like the civet in SARS-CoV (2002) and the camel in MERS-
CoV (2012) (Wang & Anderson, 2019; & Luk et al., 2019). Clusters of cases of the 2019 novel
coronavirus (2019-nCoV) infection according to Yang & Shen (2020), Velavan & Meyer (2020),
Shereen et al. (2020), and Liu & Wang (2020) were reported to be epidemiologically linked to the
Huanan Seafood Wholesale Market where live animals mixed with illegal wildlife are traded (Yang et
al., 2020). However, some studies suggest that the 2019-nCoV might have originated from either of
the two laboratories, 280 meters and 12 kilometers away from the Seafood Market in Wuhan, that
hosts bats including the Rhinolophus affinis where its tissue samples were believed are the source of
pathogens (B. Xiao & L. Xiao, 2020). Even so, more evidence is still needed to prove the claims. It is
still unclear which animal acts as the intermediate host (or if there isn’t any) which brought the bat
coronavirus to human hosts through homologous recombination. Multiple studies suggest the
Malayan pangolin (Manis javanica) may be the missing link (Lam et al., 2020; Weston & Frieman, 2020;
T. Zhang et al., 2020; Ye et al., 2020; & P. Zhou et al., 2020) by getting infected via the poop and the
saliva of the bat that is sold in the same wet market or may actually be a natural host (C. Zhang et al.,
2020b) due to the fact that they are caught and being used for medicinal purposes. The SARS-CoV-2
virus, suggested by Guo et al. (2020) and X. Tang et al. (2020), are classified to two prevalent evolution
types which are the S-type and the L-type. The S-type accounts for 30% of the infections that occurred
and is less severe and aggressive while the L-type accounts for 70% of the infections that occurred
and is suggested that the L type was derived from S type which became evolutionarily more aggressive
and contagious (Guo et al., 2020).
Animal-to-human transmission is the main exposure method because the first cases of the
COVID-19 disease were associated with direct exposure to the Huanan Seafood Wholesale Market of
Wuhan, however, succeeding cases were not related to animal-to-human transmission according to
the World Health Organization, Sohrabi et al. (2020) and Arabi et al. (2020). The spread of the SARS-
CoV-2 virus among humans was identified to be caused by human-to-human transmission which is
transmitted mainly through close contact of respiratory droplets such as tears and body fluids,
especially droplets that are created when people sneeze or cough (Q&A on coronaviruses (COVID-
19), 2020; How Coronavirus Spreads, 2020; D. Tang et al., 2020; & She et al., 2020). It is also
contracted from touching fomite surfaces, followed by touching the parts of your face and be exposed
to the mucous membranes of the eyes, mouth, or nose (Q&A on coronaviruses (COVID-19), 2020;
How Coronavirus Spreads, 2020; Singhal, 2020; & T. Lai et al., 2020). These fomite surfaces, where
the virus can stay for a period of time, are aluminum, latex, and copper, where the virus stays for 8
hours; 24 hours in cardboards; 24-72 hours in countertops, plastic, and stainless steel; and 120 hours
in glass and wood (van Doremalen et al., 2020; Morawska & Cao, 2020; & World Health
Organization). Evidence has also been found that it can be transmitted even via fecal-oral transmission
(Huang et al., 2020) and when the virus is already aerosolized and stays there for 3 hours (World
Health Organization). Not only could the virus be transmitted from symptomatic people but also
from individuals who remain asymptomatic, a person showing no symptoms (Han & Yang, 2020; &
Yu & Yang, 2020). The disease itself, due to the way it is transmitted, has caused it to be very
contagious, as any single person infected with the disease can transmit it very easily by just being near
the person and can be spread to surfaces of public transport, restaurants, and other public places such
as toilets, elevators and bus stops without proper personal protective equipment and execution of
proper hygiene (Q&A on coronaviruses (COVID-19), 2020; & Ahmad et al., 2020). After infection,
the incubation time could be within 3 to 7 days and up to 2 weeks (Q. Li et al., 2020; & Xiao & Torok,
2020) where the Series interval could be within 4 days and the virus has an estimated R 0 = 2.4 (R-
naught) (Ferguson et al., 2020) or in other words, on average, each patient transmits the infection to
an additional 2.4 individuals (Fig. 6). The R-naught or the reproductive ratio is a very important factor
why the virus spreads so quickly and it tells us how many people can one infected individual pass the
virus. Along with it is the Series interval that tells us the time it takes the infected individual to pass
the virus and cause an infection to another individual. Both the Rnaught and Series interval will show
the rate of transmission of the virus where if an infected individual were to pass the virus to two
uninfected persons and now the two infected persons will infect another two uninfected persons each
and so on. In a span of 8 days or a day after 1 week, the first infected individual has passed the virus
to 6 people and after another 8 days, there will be an additional 24 persons infected. The high
transmission rate shows how we are having such a high incidence within just a few days because it has
a relatively smaller Series interval and a relatively higher Rnaught.
There are types of identifying transmissions such as the Imported Case, Local Transmission
and Community Transmission. The term Imported Case is when a person that has acquired the disease
travels from one country to another, this term has become widely used within the discussion of
COVID-19, as it is highly contagious (Niehus et al., 2020). The first case in the Philippines was in
Manila, which is an imported one, due to the fact that patient zero is from Wuhan, China (Department
of Health, 2020). Some further cases are classified as Local Transmission which is when a disease
spreads from someone within a household to another within the same household or nearby house
(Illinois Department of Public Health, 2020). A larger spread would be called a Community
Transmission, wherein more than one member of a community is affected due to the spread of a
disease as well as of possible further cases where the place of transmission is undetected (Longini &
Koopman, 1982). A community case in the Philippines was first confirmed around the sixth of March
this year, with two additional people confirmed to have contracted COVID-19 (Republic of The
Philippines Department of Health, 2020).

Figure 6. Process of transmission of SARS-CoV-2

Fig. 6. SARS-CoV-2 started from its natural host, the horseshoe bats of the species Rhinolophus affinis and is transmitted to humans due to exposure from
the wet market in Wuhan, China which led to human-to-human transmission because of the spread of respiratory droplets. It is also suggested that the
Malayan pangolin (Manis javanica) is the intermediate host for animal-to-human transmission.

Chapter 3
Case Reports

As of April 20, 2020, there are about 2,160,207 confirmed cases worldwide and 25,291
confirmed cases in South-East Asia according to the World Health Organization. As for the
Philippines, the Department of Health reports 6,459 total numbers of confirmed cases (Fig. 7). The
first confirmed case that tested positive of the 2019-nCoV infection on January 30, 2020 was an
asymptomatic 38-year-old female Chinese patient under investigation (PUI) who arrived in the
Philippines from Wuhan, China via Hong Kong last January 21, 2020. The woman is classified as an
Imported Case with no evidence of local transmission and has recovered and has tested negative twice
on February 10, 2020 but Health Undersecretary Eric Domingo could not confirm if the woman has
already flown back to China since her release from the hospital on February 8, 2020. However, the
companion of the first confirmed case, a 44-year-old male Chinese was admitted for pneumonia on
January 25, 2020 after experiencing fever, cough, and sore throat but died on February 1, 2020 even
though the patient showed signs of improvement, the condition of the patient deteriorated within his
last 24 hours. The third confirmed case that tested positive on February 5, 2020 was a 60-year-old
female Chinese patient under investigation (PUI) who arrived in Cebu City from Wuhan, China via
Hong Kong last January 20, 2020, then traveled to Bohol thereafter where she was admitted on January
22, 2020 due to fever and coryza. The results of the patient came back negative last January 29 and
30, 2020 from the sample that was taken last January 24, 2020 at the Victorian Infectious Diseases
Reference Laboratory in Australia and the Research Institute for Tropical Medicine (RITM) and was
discharged and was allowed to return to China via Cebu last January 31, 2020. However, on February
3, 2020, the Department of Health was notified by the RITM that a sample taken on January 23, 2020,
tested positive for 2019-nCoV making her the third confirmed case that tested positive of the 2019-
nCoV infection in the Philippines. On March 6, 2020, DOH reported two additional confirmed cases
in the Philippines, bringing the total of COVID-19 cases to five (5). The fourth case is a 48-year-old
male Filipino with travel history to japan and came back to the Philippines last February 25, 2020. He
experienced chills and fever beginning March 3, 2020 and had sought medical consultation. Results
tested positive on March 5, 2020. The fifth confirmed case and the first case of local transmission is a
62-year-old male Filipino with known hypertension and diabetes mellitus, who experienced a cough
with phlegm last February 25 despite no travel history. He also had sought medical consultation last
March 1, 2020, was admitted with severe pneumonia, and on March 4, 2020, he was tested positive.
The sixth case in the Philippines was confirmed on March 7, 2020 and is the wife of the fifth case.
She was admitted to RITM on March 5. On March 8, 2020, 4 new confirmed cases were reported,
bringing the total in the country to ten. The seventh case is a 38-year-old Taiwanese with no travel
history and has a history of contact with a Taiwanese foreign national who was a positive case, and
his symptoms started last March 3. The 8th case is a 32-year-old Filpino male who had a travel history
to japan within the past 14 days. His symptoms began on March 5 and was admitted to a private
hospital. The ninth case is an 86-year-old American male with a travel history to the United States of
America (USA) & South Korea. His symptoms began on March 1 and was admitted to a private
hospital. The tenth case is a 57-year-old Filipino male with no travel history outside of the country
and was reported to have had contact with a confirmed case. On March 9, 2020, DOH reported ten
new positive cases of COVID-19, bringing the total to twenty. The ten new cases are all Filipino.
PH11 is a 72-year-old male with no travel history and his date of onset of symptoms are unknown.
PH12 is a 56-year-old male who had travelled from the United Arab Emirates (UAE) and his
symptoms, which is cough and fever, began on February 29, 2020. PH13 is a 34-year-old male who
had a travel history to Australia and his fever began on February 28, 2020. PH14 is a 46-year-old male
with no travel history or exposure to a positive case and his cough and fever began on February 25,
2020. PH15 is a 24-year-old male whose travel history AND exposure to a positive case is unknown
and his symptoms began on March 1, 2020. PH16 is a 70-year-old male and PH17 is a 69-year-old
woman, the wife of PH16, who both had travelled from Indonesia, had the same date of onset of
symptoms which is March 1, 2020. PH18 is a 41-year-old male who came from Taiwan and his
symptoms began on February 26, 2020 and was admitted to Tricity Medical Center, along with PH19
who is a 46-year-old female, the wife of PH18. The last case reported for March 9, 2020, is PH20 who
is a 48-year-old male who had a travel history to Japan, symptoms began on Feb 29 and was admitted
to RITM. Confirmed cases in the Philippines increased rapidly due to lack of knowledge about
handling the new virus.
There were notable cases recorded such as the case of Sen. Aquilino “Koko” Pimentel III who
repeatedly broke 14-day quarantine for visiting the S&R Membership Shopping Club in Bonifacio
Global City and for visiting the Makati Medical Center despite being positive for the SARS-CoV-2
virus; the youngest fatality of the COVID-19 infection in the Philippines was confirmed by the
Department of Health (DOH) on April 14, 2020, a 29-day-old infant from Batangas province was
rushed to the hospital because of shortness of breath, he was diagnosed of pneumonia after and died
of late-onset sepsis due to severe respiratory infection; an 83-year-old woman from Sta. Rosa, Laguna
became the oldest person to recover from COVID-19 on March 31, 2020 which gave a ray of hope
amid the COVID-19 pandemic which has been fatal to elderly people and people with pre-existing
medical conditions (GMA News Online, 2020); 70 confirmed cases of Filipino crews from the
Diamond Princess Cruise Ship which are currently admitted in Tokyo, Japan and the other 458 Filipino
crews and the team that brought them home will be placed under quarantine, a stricter one than of
the filipinos who came from Wuhan, China (CNN Philippines, 2020); there have been 651 confirmed
cases of overseas filipino workers (OFW), 84 deaths, and 188 recoveries as of April 11, 2020 reported
by the Department of Foreign Affairs (DFA); over 700 doctors, nurses and other healthcare workers
were infected by COVID-19 as announced by DOH last April 17, 2020. 339 doctors have contracted
COVID-19, while 242 nurses tested positive, and sadly, 22 health workers have died. DOH also
announced that a total of 766 healthcare workers have been infected. This total number is a three-fold
increase from the count that DOH reported on April 8, 2020, which they said the total was at 252
health workers that tested positive including 152 doctors and 63 nurses; In a jail in Quezon City, 18
people, which includes 9 inmates and 9 personnels, tested positive for COVID-19 according to the
spokesperson of the Bureau of Jail Management and Penology (BJMP) Xavier Solda last April 17,
2020. The infected inmates were immediately isolated from the detainees and were brought to a
quarantine facility in Payatas while the employees afflicted with the virus were told to go through self-
quarantine at home as common symptoms such as cough and sore throat were observed. Last March
25, 2020, the BJMP reported that an inmate in the same jail died of suspected COVID-19 because the
autopsy report said it was due to hypertension and a heart condition, and noted that the inmate might
have “possible Covid-19" as a "contributing condition" but it was declared that the 9 inmates and 9
personnels who tested positive for the contagious respiratory disease have no known exposure to the
suspected case.
 Last April 2, 2020, the National Capital Region (NCR) was identified as the Philippine
epicenter of the coronavirus crisis as it still has the greatest number of coronavirus disease 2019
(COVID-19) cases at over 4,593 in the Philippines as of April 20, 2020 (Fig. 8).
Last April 17, 2020, the epidemiology bureau assessed 3222 close contacts on the confirmed
cases of COVID-19 and reported that there have been 18 clusters of infected. There are also 17
certified labs for COVID-19 testing and 47 under certification process.
On April 14, 2020, the DOH released the Administrative Order No. 2020-0013 in which the
initial classification such as Patients Under Investigation (PUI) and Persons Under Monitoring (PUM)
is replaced with Suspect, Probable, and Confirmed (Table 1).

Old Classification of Individuals for COVID-19 New Classification of Individuals for COVID-
19

Not classified as a Person Under Monitoring Not a COVID-19 Case

(PUM) or a Patient Under Investigation (PUI)

Classified as a Person Under Monitoring (PUM) Not included in the New Classification of
CoViD-19 Cases

Classified as a Patient Under Investigation Classified as a Suspect Case if a person:

(PUI) (mild, severe or critical) without test - has an influenza-like illness (≥38°C
results or haven’t undergone testing fever, cough, sore throat)
- has a fever, cough, or breathing
difficulties
- has suddenly acquired a lung disease
with severe symptoms that requires
hospitalization
- has traveled or lived in a place where
local transmission of COVID-19 has
been reported within 14 days before the
symptoms started to show
- had a close contact with a Confirmed or
Probable Case of COVID-19 within 14
days before the symptoms started to
show
- is 60 years old and older
- has a high-risk pregnancy
- has pre-existing health diseases
- is a health worker

Classified as a Patient Under Investigation Classified as a Probable Case if a person/’s:

(PUI) (mild, severe or critical) with no - is already a Suspect patient
confirmed or approved result of test - testing results are uncertain, or the
testing was done in an unofficial
laboratory that conducts RT-PCR Test

Classified as COVID-19 Positive Classified as a Confirmed Case if a person has

tested positive with COVID-19 in the RT-PCR
Test

Table 1. Comparison of Old and New Classification of Individuals for COVID-19

Table 1. The Department of Health replaces Person Under Monitoring (PUM) and Patient Under Investigation (PUI) classification of individuals for
COVID-19 with Suspect, Probable, and Confirmed Cases aligned with the case definition of the World Health Organization under the Administrative
Order No.2020-0013. The new classification aims to have uniformed reporting to better focus our steps on fighting the COVID-19.

Despite the increasing rate of Confirmed Cases and Death Tolls, last April 15, 2020, the
number of patients who have recovered from the coronavirus disease in the Philippines reached 353,
surpassing the number of COVID-19 fatalities reported in the country which stood at 349. This
continued up until April 20, 2020 with a number of 428 deaths and 613 recoveries (Fig. 7) and resulted
in an increase in fatality rate of 6.636% than in April 1, 2020 where we had a fatality rate of 4.15%.
These results showed that the Philippines should have mass testing before lifting its Enhanced
Community Quarantine to lower the fatality rate. The Department of Health has reported that they
are already undergoing 4000 COVID-19 testing and are still aiming for 8000 COVID-19 testing a day.
Also recoveries rise as doctors' index of suspicion rises because despite waiting for the test results,
doctors are already treating probable cases according to the guidelines of the Philippine Society of
Microbiology and Infectious Disease (PSMID).

Figure 7. COVID-19 Tracker for Philippines as of April 20, 2020

Fig. 7. The Department of Health recorded 6,459 Confirmed Cases, 3,199 patients currently admitted, 428 deaths, and 613 recoveries as of April 20,
2020. The diagrams on the second row shows the daily reports on confirmed cases, admissions, deaths, and recoveries and at some point, in the month
of April, there has been a peak and its numbers have lessened since then. The diagrams on the third row shows the age and sex distributions of what sex
and age are more likely to have the highest and lowest numbers. Confirmed cases of COVID-19 are seen higher in people aged 30-34 years old, with
males having a few more cases than females. Meanwhile, the least infected age group are those aged 5-9 years old. The age groups 25-29 and 30-34 years
old have two of the most numbers of admitted cases with admitted cases being more common in females and males in the age grou ps 25-29 and 30-34
years old respectively. Males aged 65-69 years old are the most likely to suffer fatalities than any other age groups and most of the deaths recorded were
male. In terms of recoveries, people, mostly males, aged 50-54 years have the most chance of recovering from the disease as they have the greatest
number of recoveries.
 Figure 8. COVID-19 Tracker for the National Capital Region (NCR) of the Philippines as of April 20, 2020
Fig. 8. The Department of Health recorded 6,459 Confirmed Cases, 4,593 patients currently admitted, 281 deaths, and 422 recoveries as of April 20,
2020 in the National Capital Region (NCR) of the Philippines.

Chapter 4
Systematic Examination and Clinical Diagnosis

In this chapter, the procedure of how the systematic examination is done to look for any
possible medical signs or symptoms, that range from mild to severe, of COVID-19; and how medical
professionals diagnose patients by conducting appropriate tests to determine if COVID-19 is the cause
of a person's symptoms and signs. As mentioned earlier, patients with COVID-19 can either be
symptomatic or asymptomatic. Reported cases of the respiratory infectious disease namely COVID-
19 showed symptoms of shortness of breath (Poyiadji et al., 2020; & Sohrabi et al., 2020), cough
(Yang et al., 2020; & Sohrabi et al., 2020), sore throat (Young et al., 2020; & Singhal, 2020),
expectoration (K. Li et al., 2020; & Yang et al., 2020), headache (Y. Li et al., 2020; & Singhal, 2020),
loss of smell and taste (Baig, 2020; & Yan et al., 2020), dyspnea (Kanne et al., 2020; & Gu et al., 2020),
and chest tightness/pain (Su et al., 2020; & Deng & Peng, 2020), due to either or both upper and
lower respiratory tract infection (Gautret et al., 2020), and fever (Ahmad et al., 2020; Albarello et al.,
2020; Sohrabi et al., 2020; J. Chan et al., 2020b; & J. Chen et al., 2020). There are also some symptoms
that appear such as muscle pain (L. Tan et al., 2020; & Hormati et al., 2020), myalgia (Sohrabi et al.,
2020; & Singhal, 2020), arthralgia (Hu et al., 2020; & K. Chan et al., 2020), and fatigue (Ungaro et al.,
2020; & Singhal, 2020). There also have been increasing rates of COVID-19 patients with confirmed
gastrointestinal (GI) symptoms such as diarrhea (Sohrabi et al., 2020; & Hormati et al., 2020), nausea
(Hormati et al., 2020; & Gu et al., 2020), constipation (Hormati et al., 2020; & D. Sun et al., 2020),
vomiting (Sohrabi et al., 2020; & Hormati et al., 2020), loss of appetite (Luo et al., 2020; & Lechien et
al., 2020), epigastric pain (Hormati et al., 2020; & Lechien et al., 2020), and melena (Hormati et al.,
2020; & Cavaliere et al., 2020), due to the SARS-CoV-2 being almost identical to the SARS-CoV that
developed severe GI symptoms (Hormati et al., 2020; Sellevoll et al., 2020; & Deng, 2020). There is
still a chance of a much higher rate of emerging gastrointestinal symptoms because there is one
possible route for the movement of SARS-CoV-2 into the digestive system via “trachea-esophagus-
ileum-colon” (He et al., 2020). As single-cell transcriptome analysis showed ACE2, the entry receptor
for SARS-CoV-2 and is highly expressed in alveolar type 2 (AT2) cells in the lungs, esophagus upper
and stratified epithelial cells and enterocytes from ileum and colon (Gu et al., 2020). All of these
symptoms can be classified as mild, moderate, severe, or critical symptoms depending on its
severeness. Persons who have shown mild symptoms are advised to stay at home and quarantine
themselves for 14 days and wait for the order of your local health authority; persons who have shown
severe symptoms are authorized to be hospitalized to be treated in your local health hospitals; and
persons who have shown critical symptoms are authorized to undergo intensive care. Comorbidities
such as diabetes, hypertension, RNAemia, cardiovascular diseases, chronic respiratory diseases, cancer,
liver injury, and digestive system diseases (Yang et al., 2020; Ungaro et al., 2020; Ahmad et al., 2020;
& Mao et al., 2020) are also examined among patients because patients with underlying conditions,
especially among older people, are more prone to get infected by the virus (Sinha et al., 2020). It will
quickly spread inside the body which will lead to multiorgan system failure due to its weaker immune
system and will result in a higher risk of fatality (Zheng et al., 2020; & Jordan et al., 2020); and together,
the medical history and the physical examination help to determine a diagnosis and devise the
treatment plan.
Persons with mild to moderate symptoms and asymptomatic people who has traveled or lived
in a place where local transmission of COVID-19 or had a close contact with a Confirmed or Probable
Case of COVID-19 or is a health worker that took care of a COVID-19 infected patient are advised
to take the real time Reverse transcription polymerase chain reaction (real time RT-PCR) (Table 2).
The real time RT-PCR is the most sensitive technique and the most reliable for mRNA detection from
any pathogen, including a virus. RT-PCR is used for detecting coronavirus by collecting
nasopharyngeal swab samples. RNA is used as a template and be reverse transcribed into
complementary DNA (cDNA), using reverse transcriptase and PCR procedure is then used to amplify
the cDNA by denaturation, heat denaturing the double-stranded DNA (dsDNA); annealing, primers
align to the single DNA strands; and elongation, extending the primers using DNA polymerase. This
cycle is repeated approximately 20-40 times and results in having new copies of the viral DNA sections
are built, the marker labels attach to the DNA strands and then releases a fluorescent dye, which its
amount is tracked and measured by the machine's computer, and presented in real time on the screen.
The virus' presence is confirmed when the fluorsecence's amount goes over a certain level. Fewer
cycles means the viral infection is more severe. Antibody test is a rapid test kit to determine if a person
is infected with SARS-CoV-2. If the test kit detects Immunoglobulin M (IgM), it tells that the patient
has an ongoing illness and can be infectious and it appears after 5-7 days after infection or the acute
phase. If the test kit detects Immunoglobulin G (IgG), it tells that the COVID-19 infection is ending
and the patient is recovering where the patient’s immune system is starting to build up again, known
as convalescent phase.
For persons under mild symptoms, if you have a fever, check the temperature every 4 days;
take paracetamol at 37.5 degrees Celsius and above (drink every 4 hours if the fever does not stop but
stop if there is no fever); bathe daily if possible; do not wear duplicate clothes or scrub excessively;
make sure the room is air-conditioned properly; and drink plenty of water, fresh fruit juice and mild
tea. If you have a cough and sore throat, drink plenty of water and take the prescribed medications;
avoid harmful substances such as dust, plant pollen, perfume, and animal fur; drink salabat; soak warm
water with salt; and use cough drops. Persons who are positive of COVID-19 with mild to moderate
symptoms that are close to having severe symptoms are required to be hospitalized (Fig. 9) (Table 2).
The patients that were admitted are also required to take a complete blood count (CBC), X-ray and
computerized tomography (CT) scan (if available) in order to know their current situation. The
diagnosis in blood watches out for a decrease in lymphocyte count. Severe and critical cases such as
SARS, ARDS, and SIRS are immediately taken to the Intensive Care Unit (ICU) where patients are
connected to a life support where dextrose and ventilatory support systems are attached to them
(Table 2). For the severely and critically ill patients, they are required to take a complete blood count
(CBC) and comprehensive metabolic panel (CMP) in which their diagnosis in blood watches out for
decrease in lymphocyte count; increase in aspartate aminotransferase (AST), alanine aminotransferase
(ALT), and bilirubin levels; elevated blood urea nitrogen (BUN) and creatinine; increase in C-reactive
protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin 6 (IL-6); increase lactate
dehydrogenase (LDH); and elevated d-dimer levels, increase in ferritin, ck-mb, and troponins.

Symptoms/Signs Test Actions to be taken

if a person has an influenza-like illness (≥38°C fever, RT-PCR Self-Isolation or contact

cough, sore throat) a professional healthcare
provider

if a person has suddenly acquired a lung disease with RT-PCR Contact a professional
severe symptoms that requires hospitalization healthcare provider
 if a person has a fever, cough, or breathing difficulties RT-PCR Self-Isolation or contact
a professional healthcare
provider

if a person has traveled or lived in a place where local RT-PCR Self-Isolation for 14
transmission of COVID-19 has been reported within 14 days
days before the symptoms started to show

if a person had a close contact with a Confirmed or RT-PCR Self-Isolation for 14-
Probable Case of COVID-19 within 14 days before the days
symptoms started to show

if a person is a health worker that took care of a RT-PCR Self-Isolation for 14

COVID-19 infected patient days

If a person shows pneumonia-like symptoms (cough, Chest CT Self-Isolation for 14

sputum, fever, dyspnea, pleuritic chest pain) days

Leaning on a more serious case, if a person is suspected Blood tests Take note of your illness
to have sepsis or is showing sepsis symptoms and physical
examination

Leaning on a more serious case, if a patient is showing Electrocardi Intensive Care Unit
symptoms of cardiac injury ography and
echocardiog
raphy

If a person is showing signs of hypoxemia (shortness of Pulse Request an oxygen

breath, confusion, fast heart rate, coughing, wheezing) oximetry therapy treatment

If a person is showing a respiratory rate of ≥ 30 Chest X-ray Consult a medical

breaths/min (tachypnea) or CT scan professional for the
proper test

Table 2. Clinical diagnosis for a suspected COVID-19 case.

Table 2. The table shows the common symptoms that a COVID-19 case can have. For each type of symptoms, a specific test is given to a suspected
case to identify whether there is an underlying disease. The specified 'actions to take' also guides the person on what to do if ever they are presented with
the symptoms or signs.

Figure 9. Medical Signs of Infection Requiring Hospitalization

Fig. 9. In a numerical order, the list of medical signs show their severity by being marked by a color, orange to red. From numbers 2 to 4, they are
marked as orange which are less serious, they are the signs that are usually present in patients with COVID-19. The upper picture on the right shows a
person's alveoli that is affected by the COVID-19 virus. Number 5 and 6 starts being severe, and this stage requires emergency action. The lower picture
on the right shows a CT scan of a person's lungs that has pneumonia, framed by the blue square which has white spots inside of it, indicating fluid in
the lungs.
 Chapter 5
Effects of SARS-CoV-2

After a person has contracted the SARS-CoV-2 virus, the virus will target the epithelial cells
in the respiratory tract (Ahmad et al., 2020) particularly the ciliated bronchial epithelial cells and type-
II pneumocytes in the lungs (Brake et al., 2020; Weston & Frieman, 2020; Khan et al., 2020 & Bonilla-
Aldana et al., 2020). The spike glycoprotein guides the virus and utilizes the angiotensin-converting
enzyme 2 (ACE2) (Fig. 5), a transmembrane receptor on mammalian hosts, to enter the human cells
(Letko et al., 2020; Y. Zhou et al., 2020 & C. Zhang et al., 2020b) by direct membrane fusion between
the virus and plasma membrane (H. Wang et al., 2008; Shereen et al., 2020; & X. Li et al., 2020) (Fig.
1) with the help of the hemagglutinin-esterase glycoprotein (HE), found in only a subset of
coronaviruses, but its role in the virus life cycle has not been well established (Y. Tan et al., 2004), and
the transmembrane serine protease 2 (TMPRSS2), suggested by X. Li et al. (2020). SARS-CoV-2 virus
is a positive-sense single-stranded RNA (+SSRNA) virus that utilizes +SSRNA as its genetic material.
One third of the +SSRNA encode for a set of subgenomic mRNAs which are required for accessory
proteins as well as for the structural proteins and two-thirds of the +SSRNA exhibit the overlapping
replicase genes open reading frame 1a (ORF 1a) and open reading frame 1a (ORF 1ab) (Krichel et al.,
2020). When the virus has finally been engulfed inside the cell, the +SSRNA is released into the
cytoplasm and is translated into accessory protein, structural protein and two large polyproteins, pp1a
(nsp1–11) and pp1ab (nsp1–16) that were translated from the ORF 1a and ORF 1ab (Krichel et al.,
2020; & Ahn et al., 2012), using the cell’s ribosomes which are then cleaved into small products by
viral proteinases (Shereen et al., 2020; & X. Li et al., 2020). The +SSRNA can also use an enzyme
namely RNA-dependent RNA polymerase (RdRP, also named nsp12) that belongs to virus, to
produce a series of subgenomic mRNAs by discontinuous transcription (Shereen et al., 2020; &
Pinzón et al., 2019) which are subsequently assembled, along with the viral proteins such as the spike
glycoprotein (S), hemagglutinin-esterase glycoprotein (HE), the membrane protein (M), the small
envelope protein (E), and the nucleocapsid protein (N) (Schelle et al., 2005; Shereen et al., 2020; X. Li
et al., 2020 & C. Wu et al., 2020), using proteinases, into virions in the endoplasmic reticulum-Golgi
intermediate compartment (X. Li et al., 2020). It then proceeds to infect more undamaged cells that
have an ACE2 receptor after the viral shedding via vesicles (Shereen et al., 2020).
After the incubation period of SARS-CoV-2 inside the tissues of the lungs, several symptoms
start to show that were mentioned earlier and these symptoms can develop into fatal respiratory
illnesses such as pneumonia (Yang et al., 2020; & C. Wu et al., 2020), Severe Acute Respiratory
Syndrome (SARS) (C. Wu et al., 2020), Acute Respiratory Distress Syndrome (ARDS) (Yang et al.,
2020; & Ungaro et al., 2020), viral sepsis, fibrosis, hypoxemia, tuberculosis (Yasri & Wiwanitkit, 2020),
Systemic Inflammatory Response Syndrome (SIRS), ground glass opacity (GGO), myalgia (H. Zhang
et al., 2020); and other disorders such as kidney failure (C. Wu et al., 2020; Q&A on coronaviruses
(COVID-19), 2020; & Hui et al., 2020), gastrointestinal infection (H. Zhang et al., 2020; C. Zhang et
al., 2020a; & Xie et al., 2020), liver injury (C. Zhang et al., 2020a; & Yang et al., 2020) that will cause
multiple system organ failures leading to death (Yang et al., 2020; Ungaro et al., 2020; & C. Wu et al.,
2020) if not treated.
The damaged type 2 pneumocyte will then release inflammatory mediators which will stimulate
the alveolar m2 macrophages to secrete storms of cytokines such as the Interleukin 1 (IL-1),
Interleukin 6 (IL-6), and the Tumor Necrotic Factor Alpha (TNF-⍺) (Moodley et al., 2010; Feng et
al., 2012; & Fu et al., 2020), which will then enter the blood vessels that surround the alveoli and
causes it to undergo vasodilation due to the contraction of endothelial cells in the blood vessels (X.
Yao et al., 2020b). This increase in capillary permeability lets the plasma leak out of the blood vessels
and mix with the interstitial fluid and accumulate outside the alveolus which will try to compress and
enter the alveolus (Wu & Yang, 2020; & Solaimanzadeh, 2020). This will then lead to pulmonary
edema (Fig. 10), where most of the fluid buildup is in the alveolar spaces (Matthay & Zemans, 2011).
As the type 2 pneumocyte is damaged, surfactant production decreases and the surfactant
concentration inside the alveolus will drown out (Chow et al., 2020), this results in the increase in
surface tension as well as the increase in the collapsing pressure which will be followed by the collapse
of the alveolus. And due to this massive infection, debris formation occurs and these m2 macrophages
are not designed to kill and remove debris which leads to ground-glass opacities (GGO) or fibrosis,
the scarring in the lung tissues, and prevents oxygen from passing through to the blood (Fig. 11). The
alveolar collapse will decrease gas exchange and will be the cause of hypoxemia (one of the common
symptoms), which will increase the work of breathing and cause dyspnea (one of the common
symptoms), that will lead to ARDS (Wawrzeniak et al., 2019; & Gattinoni et al., 2020).
The released inflammatory mediators, IL-1, IL-6, and TNF-⍺, from the damaged type 2
pneumocyte will then attract neutrophils (Selders et al., 2017; & L. Chen et al., 2018) and these
neutrophils will start coming in the blood vessels then go inside the alveolar space (Fig. 12) where they
will try to destroy the virus, due to the continuous inflammation in the alveoli (Narasaraju et al., 2020).
The neutrophils will then release reactive oxygen species (ROS), the chemically reactive chemical
species containing oxygen, and proteases but, as they try to destroy the virus, it damages the type 1
and type 2 pneumocytes as well (Szymczak et al., 2020; & Wang et al., 2020). The damaged type 1
pneumocytes, that function as gas exchange, and the damaged type 2 pneumocytes, that produces
surfactant, will also result in increase in surface tension and lead to alveolar collapse (Wu & Zha, 2020).
As the alveoli collapses, lung consolidation occurs that alters gas exchange and causes hypoxemia.
Lung consolidation also leads to coughing (one of the common symptoms) where a productive mucus
is being coughed up. These storms of secreted cytokines, IL-1, IL-6, and TNF-⍺, travels via blood
and into the nervous system which signals the hypothalamus (the hypothalamus regulates temperature)
(Hammond et al., 1999) to trigger the increase in body temperature that results in the release of
prostaglandin E2 (PGE2) (Gupta et al., 2020) causing heat-generating effects to match a new higher
temperature set point, in short, a person will have a fever (one of the common symptoms) (Y. Liu et
al., 2020).
Hypoxemia as an effect of the alveolar collapse and results in low partial pressure of oxygen,
stimulates the peripheral chemoreceptors which triggers a reflex and causes the sympathetic nervous
system to become stimulated which leads to tachycardia as a result in an increase of heart rate (Obelez
& Domino, 2020) and tachypnea as a result in an increase of respiratory rate (Schwartz & Kramer,
2020).
When the damaged alveoli become severe which results in pneumonia (one of the severe
symptoms) and leads to ARDS, the rapid onset of widespread inflammation in the lungs, which may
also lead to SIRS, an inflammatory state affecting the whole body (Jakovac, 2020; & Song et al., 2020).
When cytokines spread into the systemic circuit via blood (Tisoncik et al., 2012), it increases capillary
permeability which then allows plasma to leak out and accumulate in the interstitial space which
decreases the blood volume; and causes vasodilation, widening of blood vessels, which will decrease
peripheral resistance resulting to septic shock (Song et al., 2020; & Tisoncik et al., 2012). Both
vasodilation and decrease in capillary permeability will cause the patient to be hypotensive and
perfusion to different organs such as the kidneys and liver decreases which will lead to multiorgan
system failure such as the intestines, heart, brain and other organs. Poor perfusion in the kidneys
results in increase in blood urea nitrogen (BUN) and creatine which shows kidney failure (Zachariah
et al., 2019; & Nissan, 2015). Poor perfusion in the liver results in the release of inflammatory enzymes
such as aspartate transaminase and (AST), alanine transaminase (ALT); and bilirubin (Giannini et al.,
2005; & Kerner et al., 2005), a waste product primarily produced by the normal breakdown of heme;
and acute phase reactant proteins such as C-reactive protein (CRP), fibrinogen, and IL-6 (Kerner et
al., 2005), which shows liver failure (Giannini et al., 2005; & Kerner et al., 2005).
In the study of G. Li et al., (2020), have found that COVID-19 caused inflammatory storms,
hypoxemia, and renin-angiotensin system imbalance that contributed to serious myocardial damage
and hypertension in COVID-19 patients. Mothers infected with COVID-19 during pregnancy, less
than 90% of them had pneumonia. Pulmonary Tuberculosis (PTB) was the most frequent unfortunate
outcome. In addition, perinatal death, cesarean, preeclampsia and miscarriage were also more common
than in the general population with a rate of 7-11% (Mascio, et al., 2020).
As the lungs get more damaged, there will be no oxygen produced to circulate throughout the
body that leads to multiorgan system failure and death.
 Figure 10. Schematic representation of alveolar damage
Fig. 10. Produced by Matthay & Zemans (2011). (a) The normal alveolus and (b) the injured alveolus in the acute phase of acute lung injury and the
acute respiratory distress syndrome. In the acute phase of the syndrome (b), there is sloughing of both the bronchial and alveolar epithelial cells; protein-
rich hyaline membranes form on the denuded basement membrane. Neutrophils adhere to the injured capillary endothelium and marginate through the
interstitium into the air space, which is filled with protein-rich edema fluid. In the air space, alveolar macrophages secrete cytokines; interleukin (IL)-1, -
6, -8, and -10; and tumor necrosis factor α (TNF-α), which act locally to stimulate chemotaxis and activate neutrophils. IL-1 can also stimulate the
production of extracellular matrix by fibroblasts. Neutrophils can release oxidants, proteases, leukotrienes, and other proinflammatory molecules such
as platelet-activating factor (PAF). A number of anti-inflammatory mediators also present in the alveolar milieu include IL-1 receptor antagonist, soluble
TNF receptor, autoantibodies against IL-8, and cytokines such as IL-10 and -11 (not shown). The influx of protein-rich edema fluid into the alveolus
leads to the inactivation of surfactant. Abbreviation: MIF, macrophage-inhibitory factor.
 Figure 11. Schematic representation of alveolar damage
Fig. 11. Produced by J. Lim et al. (2018). Newly developed diffuse ground glass opacities and con-solidation in both lung fields on chest X-ray and chest
CT scan at the admission (A, B) and the 7th day after (C, D).

Figure 12. Neutrophil migration across epithelia.

Fig. 12. Produced by Matthay & Zemans (2011). Neutrophil migration across epithelia can be considered in three sequential stages: adhesion, migration,
and postmigration. The initial stage of neutrophil transepithelial migration is characterized by adhesion of the neutrophils to the basolateral epithelial
membrane. Adhesion is mediated by ligation of CD11b/CD18 on the neutrophil surface to several molecules on the epithelial surface, including
fucosylated glycoproteins; junctional adhesion molecule C (JAM-C); and probably other, as-yet-unidentified molecules. After initial adhesion, neutrophils
crawl along the epithelial cell membrane via sequential binding to a number of epithelial cells–surface molecules. Both epithelial and neutrophil CD47
molecules are involved during this stage, and CD47 on both cell types may bind to and signal through signal regulatory protein α (SIRPα). In addition,
SIRPα probably signals via pathways that are independent of CD47 during neutrophil transepithelial migration. Once neutrophils have completely
traversed the epithelial monolayer, they adhere to the apical epithelial surface, where they resist fluid flow and mechanical forces and constitute a defense
barrier against invading microorganisms.
 Chapter 6
Prevention

COVID-19 has already infected more than a million people in the world as of now and is still
continuing to rise; which indicates that precautionary measures should be taken in action in order to
slow down and eventually stop the spread of the virus. As of now, there is still no proven medicine
that can cure the new disease; however, preventive measures can be implemented to isolate the virus
from infecting more people. There are 6 basic protective measures against COVID-19 which are,
frequent hand washing, social distancing, prohibition from touching the face, respiratory hygiene
practices, early detection and monitoring, and awareness and obedience to healthcare professionals’
advice (World Health Organization, 2019). Through these measures, both the people and the
healthcare system may be benefitted by starving the virus of hosts and eventually eradicating it. In this
chapter, these preventive measures that should halt and eventually inhibit the SARS-CoV-2 virus from
spreading, will be discussed thoroughly. Furthermore, evidence, studies, and detailed instructions will
also be covered by this chapter.

Washing of hands is a crucial element in keeping oneself safe from most viral pathogens,
including the SARS-CoV-2 virus, which causes COVID-19. According to the World Health
Organization (2019), regular and thorough cleaning of hands using an alcohol-based sanitizer or just
washing your hand with soap and water is enough to kill the virus in your hands. The virus is capable
of different types of transmission including, direct and indirect contact with other persons. Direct
transmission is done through touching the person or being touched by the person which happens to
have respiratory droplets which can be transferred to your skin and eventually can end up in your
respiratory tract. On the other hand, indirect contact happens when respiratory droplets are present
on objects that a person may touch with their hands or other parts of the body which can eventually
lead into their respiratory tract (Adnan Shereen et al., 2020). If hands are not washed properly after
contact with a contaminated surface, these infected droplets wouldn’t just infect the host but can also
spread by means of food and drink preparation and touching other people or surfaces (Centers for
Disease Control and Prevention, 2019). According to the Centers for Disease Control and Prevention
(2019), the following are the “key” times to wash hands:

Action BEFORE DURING AFTER

Preparing Food
Eating Food
Caring for someone at home who is sick
Treating a cut or wound
Using the Toilet
Cleaning up a child who has used the toilet
Blowing your nose, coughing, or sneezing
Touching an animal, animal feed, or animal waste
Handling pet food or pet treats
Touching garbage
*After you have been in a public place and touched an item
or surface that may be frequently touched by other people,
such as door handles, tables, gas pumps, shopping carts, or
electronic cashier registers/screens, etc. (Centers for
Disease Control and Prevention, 2019)
*Before touching your eyes, nose, or mouth because that’s
how germs enter our bodies. (Centers for Disease Control
and Prevention, 2019)
Figure 13: Key Times to Wash Hands

Figure 13: The key times to wash hands are indicated by the shaded boxes that correspond to an action whether hands should be washed
before, during, or after. *Areas shaded in blue highlight special hand-cleaning key times during the on-going COVID-19 pandemic.

According to the Centers for Disease Control and Prevention (2019), the proper way to wash
hands are as follows, wetting your hands with clean, running water (it may be warm or cold), turning
off the tap, and applying soap to your hands; lathering the hands by rubbing them together with the
soap (the back of the hands, in between the fingers, and under the nails.); scrubbing your hands for at
least 20 seconds; rinsing the hands well under clean, running water; and drying the hands using a clean
towel or air drying them. There are several studies that suggest the effectiveness of these methods.
Increasing washing time with soap between 15 to 30 seconds proved effective in reducing bacteria
and consequently reducing the subsequent transfer of these pathogens to objects. However, the
washing time also depends on the soap volume; its increase is found to be effective in killing bacteria
(Fuls et al., 2008).

Social distancing can halt the spread of the disease by separating healthy and infected persons.
The first and foremost purpose of social distancing is to separate one’s self from others by means of
distancing to avoid being infected or infecting other people. Recalling the transmission capability of
the virus, according to Adnan Shereen et al. (2020), the disease can be spread through respiratory
droplets through coughing and sneezing which can cause the droplets to form an Aerosol in the air.
In response to this infection risk, according to the World Health Organization (2019) that during the
COVID-19 pandemic, everyone should maintain 1-meter distance between themselves and other
people. Maintaining this distance could prevent the aerosols formed from infected respiratory droplets
to enter your airway through inhalation. During the 1918-1919 Influenza pandemic, which is the latest
pandemic before the current COVID-19 pandemic, in the United States of America, a variety of non-
pharmaceutical interventions took very important roles in the delaying the peak of infection and
reducing the mortality rate among citizens; this includes social distancing (Markel et al., 2007).
According to Markel et al. (2007), the US cities that had the greater delays before reaching peak
mortality, lower peak mortality, and lower total mortality rates are the cities that implemented
nonpharmaceutical interventions the earliest. Moreover, Markel et al. (2007), have concluded that in
creating concrete plans and healthcare protocols for future influenza pandemics, nonpharmaceutical
interventions should be alongside pharmaceutical interventions to help delay the mortality peak and
reduce the total mortality rate of infected citizens. Social distancing is often associated with “flattening
the curve” that are being used by numerous media outlets to provide mathematical evidence on the
effectiveness of social distancing. Flattening the curve pertains to the idea of reducing the peak
infection rate of the coronavirus in order for each country’s healthcare system to be able to
accommodate all infected persons within their capabilities. As stated earlier, non-pharmaceutical
solutions such as social distancing have an impact in reducing the number of infected people and their
mortality rate, this is why social distancing is a key part in “flattening the curve” since there will be
less contact with healthy and infected people due to the distance between persons. According to a
predictive model, the likelihood of people to be infected without the imposition of social distancing,
closure of schools and universities, and isolation of infected cases, it is estimated, given that the virus
has an estimated R0 = 2.4 (R-naught), the virus could infect 81% of the Great Britain’s and United
States’ population over the course of the pandemic; 510,000 deaths in Great Britain and 2.2 million
deaths in the United States (Ferguson et al., 2020). According to their analysis, these interventions
should not be lifted or eased not until there is a sufficient supply of vaccines for those who are infected.
The premature lifting of non-pharmaceutical interventions could cause the infection rate to spike again
and undermine current efforts in suppressing the virus. Moreover, it was proven that non-
pharmaceutical interventions have the ability to lower the R to less than 1, if the virus is maintained
to be suppressed, other interventions such as intensive testing could be implemented (Ferguson et al.,
2020).

Respiratory hygiene is another essential element in reducing the number of people being
infected. According to the World Health Organization (2019), respiratory hygiene means covering
with your bent elbow or tissue the mouth and nose whenever you sneeze or cough and dispose of the
tissue immediately. Recalling the ability of the virus to spread through respiratory droplets (Adnan
Shereen et al., 2020), it is a clear indication that sneezing and coughing without proper respiratory
hygiene could result in the infection of other people that you might get in contact with. According to
an article by the Centers for Disease Control and Prevention (2019), entitled Respiratory Infection
Control Measures, in the healthcare setting, there are four infection control measures that should be
incorporated into infection control practices as a component of the standard precautionary measures:

1. Visual alerts – signs that indicate the mandatory practice of respiratory hygiene and cough etiquette
must be placed at the receiving areas of buildings; this includes covering one’s cough (tips to prevent
the spread of germs and viruses from coughing, and information about personal protective equipment
(PPEs).

2. Respiratory Hygiene/Cough Etiquette – which enumerates the proper ways to contain respiratory
secretions and are to be recommended to people who are showing signs of a respiratory illness. This
includes, covering your mouth and nose with a tissue paper when coughing or sneezing, using the
nearest garbage bin to dispose of the tissue immediately after use, and performing hand hygiene). In
healthcare settings, healthcare facilities should ensure to provide tissues and no-touch receptacles for
used tissue disposal and provide dispensers of alcohol-based hand sanitizers; in sink areas, hand
washing supplies must be available such as soap and disposable towels.
3. Masking and Separation of Persons with Respiratory Symptoms – in the case of school and
workplace settings, it is recommended that with an increase of absenteeism, people who are showing
signs of respiratory illness must be given masks to contain respiratory droplets and secretions (either
ear-loop masks or surgical masks; N-95 respirators and above are not necessary for this purpose,
however, N-95 respirators could still be effective in keeping healthy people from inhaling other
airborne pathogens). Furthermore, people who are showing signs of respiratory illness must be
recommended to stay 3 feet away from others in common areas.

4. Droplet Precautions – this is used for patients that are known or suspected to show signs and
symptoms of an infectious pathogen which can be transmitted through respiratory droplets that are
generated by an infected person through coughing, sneezing, and talking (Centers for Disease Control
and Prevention, 2019). The patient should wear a mask to prevent respiratory droplets from getting
into objects or persons. Healthy people who are treating or taking care of infected persons should
isolate themselves properly and use PPE appropriately by donning masks upon entry of the patient’s
room or space. Lastly, the transport of the infected individual should be limited to only medically
necessary purposes; if movement is necessary, the patient must be instructed to wear a mask and
follow the respiratory hygiene procedures (Centers for Disease Control and Prevention, 2019).

Even though these precautions are recommended for healthcare settings, they are still effective
in reducing the spread of the disease when applied in home, school, work, and public settings. (Centers
for Disease Control and Prevention, 2019) These precautions, if prudently observed, may decrease
the infection rate in a particular area. Cumulatively, these efforts, if observed by everyone, may help
reduce the overall infection rate which can eventually lead to the decrease of mortality rate in a global
scale.

Chapter 7
Treatment Strategies

Treatment strategies for 2019-nCoV/SARS-CoV-2 outbreak and its effects are an urgent need
for the mildly ill, moderately ill, severely ill and critically ill patients. These treatment strategies can be
divided into two categories depending on the target, one is acting on the human immune system or
human cells, and the other is on coronavirus itself. In targeting the coronavirus itself, the researchers
are suggesting treatments such as blocking the ACE2 receptor, blocking the endoplasmic reticulum-
Golgi intermediate compartment, inhibit the RNA-dependent RNA polymerase (RdRP) from
replicating RNA, inhibit proteases from breaking down polyproteins needed for the structural
proteins, blocking the endosomal packaging, and destroying the infected lung itself by using off-label
or repurposed drugs for terminating SARS-CoV-2.
First treatment strategy is blocking the ACE2 receptor using chloroquine (Fig. 13a). The drug
will stop the entire cascade of the SARS-CoV-2 virus to fuse and hijack the engine and machinery of
the alveolus cell to regenerate (Vincent et al., 2005; Colson et al., 2020; Gao et al., 2020; Liu et al.,
2020; & M. Wang et al., 2020). Chloroquine has been widely used to treat human diseases, such as
amoebiasis, human immunodeficiency viruses (HIV), autoimmune diseases, and especially malaria
without harmful side effects (Vincent et al., 2005) and in this case, was found to inhibit SARS-CoV-2
infection by glycosylating the ACE2 receptor (Fig. 13a. A). On the other hand, Liu et al. (2020) also
claims that hydroxychloroquine, a more soluble and less toxic metabolite of chloroquine, will have the
same effect as chloroquine but causes less side effects and is, therefore, safer (Gautret et al., 2020;
Sahraei et al., 2020; & X. Yao et al., 2020a). It was reported that the safe dosage (6–6.5 mg/kg per day)
of hydroxychloroquine sulfate could generate serum levels of 1.4–1.5 μM in humans will inhibit SARS-
CoV-2 infection (Liu et al., 2020).
Second treatment strategy is to block the machinery (endoplasmic reticulum-Golgi
intermediate compartment) (Fig. 13b. B) and to inhibit the RNA-dependent RNA polymerase (RdRP)
of the infected cell to stop replication using remdesivir (Fig. 13b. A), a 1′‐cyano‐substituted adenosine
nucleotide analog inhibitor of RdRp (Lung et al., 2020) and a drug used in hundreds of patients with
Ebola (Ko et al., 2020; M. Wang et al., 2020; & Dong et al., 2020) but is still in phase 3 clinical testing
(Al-Tawfiq et al., 2020; & Zhang & Zhou, 2020). Results of 200 mg loading dose on day 1 followed
by 100 mg daily maintenance for 9 days showed promising results in patients (Dong et al., 2020; &
Al-Tawfiq et al., 2020). Remdesivir also binds with the human TMPRSS2 to stop the virus infection
(C. Wu et al., 2020); and brefeldin A (Verheije et al., 2008), an antiviral drug, that is produced by the
fungus Penicillium brefeldianum, that inhibits protein secretion by interfering with the function of the
Golgi apparatus (Mansour et al., 1999; & Alvarez & Sztul, 1999) but further studies and evidence are
still needed.
 Third treatment strategy is to inhibit proteases from breaking down polyproteins needed for
the structural proteins of SARS-CoV-2 using lopinavir/ritonavir (J. Lim et al., 2020; Young et al.,
2020; Stebbing et al., 2020; H. Zhang et al., 2020; & Velavan & Meyer, 2020) (Fig. 13c). Ritonavir is a
potent inhibitor of HIV-1 protease (C. Wu et al., 2020) while Lopinavir is also a protease inhibitor
developed from ritonavir (Cvetkovic & Goa, 2003). Results have shown that the SARS-CoV-2 viral
load decreased to no detectable or little coronavirus titers have been observed in patients since then
(J. Lim et al., 2020; Shereen et al., 2020; & Young et al., 2020).
Fourth treatment strategy is to block the endosomal packaging using endosomes to avoid viral
shedding using hydroxychloroquine and chloroquine to change the Ph level of the virus (Fig. 13a. B);
bafilomycin A1 (Yang & Shen, 2020), a strong inhibitor of the vacuolar type H (+)-ATPase in vitro
or endosome progression (Cervia et al., 2017); and neuraminidase inhibitors (Rothan & Byrareddy,
2020; & Murthy et al., 2020), but further studies and evidence are still needed for both the bafilomycin
A1 and neuraminidase inhibitors.
Fifth treatment strategy is to destroy the factory (infected lung cell) itself by activating T cells
(granzymes) to avoid the whole process after the entering of the virus using antibody treatment or the
convalescent plasma therapy (1980). This treatment is done by contracting plasma from recovered
patients which consists of antibodies that can help fight the virus when transferred to an unrecovered
patient. Tocilizumab and Sarilumab, approved to treat rheumatoid arthritis, are monoclonal antibody
or modified antibody drugs which can also be used to help fight the virus. Also, the antibody-
dependent cell-mediated cytotoxicity (ADCC) will help antibodies bind to the infected lung cells and
let the natural killer cells bind to the antibodies and kill the infected cell by injecting cytokine-induced
killer (CIK) or IL-15.
All of these repurposed drugs are still under clinical trials and for patients who are currently
taking these investigational drugs for COVID-19 infection, there are protocols needed to be followed
according to the requirements of the Food and Drug Administration (FDA) before giving them to the
patients. 1) Let the patient know that the drug he/she will take is not yet established as an effective
drug for covid. 2) Explain the benefits and possible side effects. 3) Let the patient know that the
prescribed off-label drug/s have no assurance of effectiveness against COVID-19. 4) Let the patient
sign the informed consent.

a) b) c)
Figure 14a, 14b, & 14c. How Chloroquine/Hydroxychloroquine,
Remdesivir, and Lopinavir/Ritonavir
Fig. 14a. Chloroquine/Hydroxychloroquine. A. Glycosylation of ACE2
inhibits viral spike protein binding and entry into the cell; B. Increase of
endosomal pH resulting in impaired virus-to-cell fusion; and C. Zinc
ionophore activity that inhibits viral RNA polymerase and replication.
Fig. 14b. Remdesivir. The adenosine nucleotide inhibits viral replication by:
A. Inhibiting RdRP; and B. Inhibiting the exoribonuclease (ExoN) that
‘proofreads’ the new RNA for fidelity.
Fig. 14c. Lopinavir/Ritonavir. A. Prevents the SARS-CoV-2 new virion
production by inhibition of viral proteases.

In anti-coronavirus therapies, the innate immune system response plays an important role in
controlling the replication of the virus inside an infected person. The researchers are suggesting
treatments that act on the human immune system or human cells to fight off the virus known as
supportive or standard care.
The current supportive or standard care system for patients infected, classified as moderately
ill to critically ill (depending on their situation and how the professional healthcare provider will act),
is to give them intravenous fluids, either in a form of Lactated Ringer's solution (LR) or Normal Saline
(NS), but in moderation to not overflow the lungs and contribute to the pulmonary edema. To reduce
the patient's fever, they will be given antipyretic drugs such as tylenol and paracetamol. To decrease
inflammatory response in the patient’s lungs, corticosteroids, but further studies and evidence are still
needed, or tocilizumab will be given to block the IL-6. For pneumonia due to bacteria, the patient will
be given antibiotics. For flu, oseltamivir will be prescribed. For severely and critically ill patients that
already have severe pneumonia, ARDS, SIRS, SARS, and other organs leading to multiorgan system
failure, ventilatory support is given to assist or replace spontaneous breathing of these patients. In
operating mechanical ventilation, there are a few things needed to be checked in order to perform it
well such as the AC volume control (not the best method due to constant changing of settings) by
lowering the tidal volume (4-6 mL per kg of body weight) to help increase ventilation and increase
diffusion through the membrane that will lead to increase oxygen, increasing respiratory rate to release
enough carbon dioxide to not cause decrease in blood pH level, and add positive end respiratory
pressure (PEEP) set only greater than 5 cm of water to open up the collapsed alveoli; and to not
aerosolized the virus by not having high flow nasal cannula and having non-invasive positive pressure
ventilation. There‘s also the bilevel ventilation, airway pressure release ventilation (APRV), inhaled
prostacyclin, paralytics (for severe neuromuscular blockade), and prone positioning to have pressure
control in lungs that will help the patient survive. As the last resort, extracorporeal membrane
oxygenation (ECMO) is given if all methods have failed.
The patient can return home after feeling better and if the doctor said the patient’s condition
is better even if the patient hasn’t taken the RTPCR result in COVID-19. The patient should still
undergo 14-day quarantine and still perform the rapid antibody testing two times with an interval of
48 hours.
There is still no vaccine available for COVID-19 but it was reported that a German company
working with US pharmaceutical giant Pfizer has begun human trials of a potential COVID-19
vaccine. The race for the vaccine is in process in which the scientists are creating a vaccine targeting
the spike proteins and the nucleocapsid using the adenovirus vector, are non-enveloped, double-
stranded (ds) DNA viral vectors with a packaging capacity of approximately 35 kb which are widely
used for gene delivery (Kaspar, 2009). The adenovirus will be engineered with the weak SARS-CoV-
2 DNA, either the spike proteins, nucleocapsid protein, or the membrane protein, to let the T cells
recognize and kill the virus or the infected cell. This T cell mediated immunity lets the adenovirus
infect the dendritic cells and take naive T cells and start educating it about the virus by killing it. The
activation and clonal expansion of the T cells will result in having memory T cells when the COVID-
19-infected cell is destroyed. B cell mediated immunity helps the antibodies neutralize the virus by
binding to the ACE2 receptors and let the M1 macrophage eat the virus via phagocytosis and kill the
virus.
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