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Evaluation
Mild to Moderate
COVID-19 Disease (Non-severe COVID-19 or Clinical Stage 1 to 3)
Mild disease is characterized by the absence of pneumonia or
hypoxia and abnormal chest imaging findings. It includes the presence of acute
onset of fever or cough with any ≥3 of the following: Fever, cough, coryza,
sore throat, diarrhea, anorexia or nausea or vomiting, loss of sense of smell
or taste, general weakness or body malaise or fatigue, headache, and myalgia.
Moderate disease features evidence of lower respiratory disease
clinically or in imaging with oxygen saturation (SpO2) of ≥94% on room air at sea level and
respiratory rate of <30 breaths/minute.
Severe COVID-19
Disease (Clinical Stage 4)
Patients with severe disease exhibit severe pneumonia clinically
and in diagnostic exams. Dyspnea, hypoxia, and/or >50% lung involvement on
imaging are present and oxygen saturation is <90% on room air.
Patients with severe COVID-19 disease have signs of severe
respiratory distress and present as follows:
- Adult: Use of accessory muscle, unable to complete full sentences, respiratory rate of >30 breaths/minute
- Children: Very severe chest wall in-drawing, grunting, central cyanosis, unable to breastfeed or drink, lethargy, convulsions, or reduced level of consciousness
Critical COVID-19
Disease (Clinical Stage 5)
Patients with critical COVID-19 disease have pneumonia and
impending respiratory failure that requires high-flow oxygen, non-invasive or
invasive ventilation, acute respiratory distress syndrome, sepsis or shock,
deteriorating sensorium, or multi-organ failure.
Comorbidities
There is an increased risk for severe COVID-19 illness in adult patients
of any age with certain underlying conditions. There is currently limited data and
information on the effects of many comorbidities on the risk for severe
COVID-19 illness. It is essential that those people at increased risk of severe
illness of COVID-19 and those who live with them protect themselves from
getting COVID-19.
Asthma
Systematic
reviews have shown that people with asthma are not at increased risk of
acquiring COVID-19. However, there is an increased risk of COVID-19 deaths in
asthmatic patients who recently needed treatment with oral corticosteroids.
It
is recommended that patients with severe asthma continue to take biologic
therapy or oral corticosteroids if prescribed. When asthma worsens, it is
recommended to increase controller and reliever medications. If appropriate, a
short course of oral corticosteroids can be taken for patients with severe
asthma exacerbations. Nebulizers should be avoided, where possible, in order to
avoid the spread of the virus. It is preferred to use a pressurized
metered-dose inhaler via a spacer except for life-threatening exacerbations. In
patients with confirmed or suspected COVID-19, spirometry should be avoided.
Cardiovascular Disease*
COVID-19
patients with cardiovascular comorbidities are common and they have a higher
risk of morbidity and mortality. Thus, cardiovascular disease prevention
strategies are essential, especially strategies that bring a wide spectrum of
possible beneficial effects.
SARS-CoV-2
counteracts the effects of angiotensin II in conditions with excessive
activation of the renin-angiotensin system. More than 25% of critical cases of
COVID-19 exhibit myocardial injury and present as acute myocardial injury and
dysfunction on presentation and myocardial injury develops as illness severity
intensifies. It can be caused by direct myocardial injury associated with
upregulation of ACE2 in the heart and coronary vessels, or it can be secondary
to molecular mimicry following the activation of adaptive autoimmune-type mechanisms
or be exacerbated by hypoxia in the context of respiratory failure.
It
is recommended to continue clinically indicated ACE inhibitor and angiotensin
receptor blocker (ARB) medications at this time.
Case
series data have shown that there is a massive inappropriate activation of the
coagulation cascade that occurs in COVID-19 patients. Low-molecular-weight
Heparin or Fondaparinux has been recommended in hospitalized COVID-19 patients.
*Please
see Cardiovascular Disease
Prevention disease management chart for
further information.
Hypertension*
Hypertension
is the most frequent comorbidity in COVID-19 patients. It is believed that the
use of ACE inhibitors contributes to the entry of SARS-CoV-2 in the cells but
present data show no association between COVID-19 and hypertension. No clinical
data showed beneficial or adverse outcomes in those who used ACE inhibitors,
ARBs, or other renin-angiotensin-aldosterone system antagonists in COVID-19.
It
is recommended to continue clinically indicated ACE inhibitor and ARB
medications at this time, and until further information becomes available, it
is recommended to treat hypertensive patients based on current clinical
practice guidelines.
*Please
see Hypertension
disease management chart for further information.
Diabetes Mellitus
Individuals
with diabetes with poor glycemic control have a high risk of severe illness or
poor prognosis from COVID-19. Mechanisms that can increase the ability of
COVID-19 to impact patients with diabetes include decreased viral clearance, diminished
function of T-cells, increased susceptibility to hyperinflammation and cytokine
storm, and the presence of cardiovascular disease.
The
poorer prognosis of patients with diabetes might be caused by the syndromic
nature of the disease and the presence of hyperglycemia, older age, and comorbidities
(in particular hypertension, obesity, and cardiovascular disease) that increase
the risk.
For
patients with mild COVID-19, glucose-lowering therapies should be continued, and
blood glucose monitoring should be performed. In hospitalized patients with
severe COVID-19, there might be a need to modify their diabetes therapy including
withdrawing ongoing treatments and initiating insulin therapy depending on the
severity of the COVID-19 disease.
Insulin
and dipeptidyl peptidase-4 (DPP-4) inhibitor therapy may be continued in
patients with COVID-19. Antiviral drugs such as Lopinavir and Ritonavir may
lead to hyperglycemia and may worsen glycemic control. Glucocorticoid use may
cause worsening of insulin resistance or glycemic control, sustaining
gluconeogenesis, and marked hyperglycemia.
Dyslipidemia
Generally,
all individuals on lipid-lowering therapy should continue medications even during
the pandemic or in patients with an increased risk of COVID-19 infection. In
patients with confirmed COVID-19, lipid-lowering therapy may still continue with
care on the avoidance of drug interaction between lipid-lowering medications and
drugs that are being used for the treatment of COVID-19, especially in patients
with abnormal liver function tests.
Statin
therapy initiation may be considered in high-risk patients during severe
manifestations of COVID-19 to prevent some of the life-threatening
cardiovascular complications. Some studies have shown that statin therapy helps
in plaque stabilization, cholesterol reduction, cardiovascular risk prevention,
and inflammation reduction. They also have potential antiviral properties.
Obesity
Obesity
has been associated with more severe illness of COVID-19 and death. Abdominal
fat has a detrimental ventilatory effect as there is a need for more mechanical
ventilation for those with a body mass index (BMI) of >35 kg/m2
than those with a BMI of <25 kg/m2.
Intravascular disseminated coagulation may develop causing impaired lung
perfusion in patients with severe COVID-19. Obesity is associated with immune
dysregulation and chronic inflammation that could cause organ failure in
patients with COVID-19.
SARS-COV-2 Reinfection and Breakthrough Infection
Reinfection
Repeat
testing for evaluation of reinfection should be considered only for those
patients who have fully recovered from the initial SARS-CoV-2 infection but
present with symptoms compatible with COVID-19 with no obvious alternative
etiology.
Reinfection
often occurs in those with weak immune response during the initial infection,
as is usually reported in those with mild illness. It may also occur as initial
immune responses wane over time. The majority of cases occurred in individuals
who were unvaccinated and there were a few patients who were symptomatic during
reinfection than during the initial infection. Treatment of reinfection is the
same as that for initial infection.
Breakthrough Infection
Breakthrough
infection is the infection that occurs in patients who completed the primary
vaccine series and is less likely to lead to severe illness than in infection
in unvaccinated individuals. The treatment is the same as that for an initial
infection.
Principles of therapy
Mild to Moderate
COVID-19 Disease
The main goal of treatment in mild to moderate COVID-19 disease
is to prevent progression to severe disease, hospitalization, or death. Other
goals include accelerating symptom recovery and viral clearance.
Symptomatic treatment is recommended such as antipyretics for
fever and pain, adequate nutrition, and appropriate rehydration by oral fluids and
isolation at home or in temporary treatment and monitoring facilities.
The patient should be informed of the signs and symptoms of
severe disease or complications and should be advised to seek immediate care
once observed. Antibiotic therapy or prophylaxis is not recommended among these
patients.
Severe COVID-19
Disease
In patients with severe COVID-19 disease, the site of treatment
should have a pulse oximeter, functioning oxygen systems, and disposable,
single-use, oxygen-delivering interfaces (nasal cannula, Venturi mask, mask with
reservoir bag).
Supplemental oxygen therapy should be immediately administered
to those with emergency signs (eg obstructed or absent breathing, severe
respiratory distress, central cyanosis, shock, coma and/or contusions) or to
those without emergency signs but with an SpO2 of
<90%.
Fluid management should be used cautiously in patients without tissue
hypoperfusion and fluid responsiveness. The use of nebulizers is not
recommended. Antivirals (eg Remdesivir) can be given to hospitalized patients with
severe disease.
Nonpharmacological
Isolation
Isolation is the separation of infected COVID-19 patients
from those who are not infected. Isolate asymptomatic COVID-19-positive
patients and individuals with COVID-19 symptoms who can recover at home.
During
isolation, the patient should monitor symptoms and if there are warning signs,
seek emergency care. Warning signs include difficulty breathing, persistent or
new-onset fever, respiratory rate >25, persistent pressure or pain in the
chest, new confusion, inability to wake or keep awake, and bluish lips or face.
If
possible, stay in a separate room from other members of the household and use
separate bathrooms during isolation. Avoid contact with other members of the
household and pets and do not share personal household items (eg cups, towels,
utensils). Advise patients to wear a mask if around other people.
Criteria
for Releasing COVID-19 Patients from Isolation
Symptomatic
patients may be released from isolation in 5 to 7 days after the onset of
symptoms, after fever resolution for at least 24 hours without the use of
fever-reducing medications, and improvement of other symptoms.
Asymptomatic
patients may be released from isolation 5 days after a positive test for
SARS-CoV-2. Severely ill and immunocompromised patients may be released from
isolation at least 10 days up to 20 days after symptom onset as they may
produce replication-competent virus beyond 10 days or may need additional
testing and infectious disease expert consultation for an appropriate duration
of isolation and precautions.
Pharmacological therapy
Antivirals
Remdesivir
Remdesivir
is a monophosphate prodrug that binds to viral RNA-dependent RNA polymerase and
inhibits viral replication through premature termination of RNA transcription.
It is the first United States Food and Drug Administration (US FDA)-approved
COVID-19 treatment for adults and children ≥12 years old and weighing at least
40 kg requiring hospitalization. It should only be administered in the hospital
or in a healthcare facility capable of providing acute care.
It
is recommended in hospitalized patients with severe COVID-19. Remdesivir
treatment for 5 days is suggested for patients on supplemental oxygen but not
on mechanical ventilation, high-flow devices, non-invasive ventilation, or
extracorporeal membrane oxygenation.
It
is recommended by the WHO Guideline Development Group (GDG) as a treatment
option for patients with non-severe illness at the highest risk of
hospitalization and severe COVID-19 but not for patients with critical COVID-19.
Remdesivir with Baricitinib
Remdesivir
with Baricitinib is recommended by the US FDA with emergency use authorization
(EUA) for treatment of suspected or laboratory-confirmed COVID-19 in
hospitalized adults and pediatric patients ≥2 years of age requiring
supplemental oxygen, invasive mechanical ventilation, or extracorporeal
membrane oxygenation.
Molnupiravir
Molnupiravir
is an oral potent ribonucleoside analog authorized by the United Kingdom
Medicines and Healthcare Products Regulatory Agency (MHRA) and granted by the
US FDA with EUA for use in patients with mild to moderate COVID-19 and at least one risk factor for developing severe illness, such as obesity, older age (>60
years old), diabetes mellitus, and heart disease.
It
is given conditional recommendation by the WHO for patients with non-severe
COVID-19 who are at the highest risk of hospitalization, except for children,
pregnant, and breastfeeding women. It is also recommended as an alternative
therapy to Ritonavir-boosted Nirmatrelvir or Remdesivir. It can be administered
as soon as possible following a positive COVID-19 test and within 5 days of
symptom onset. It is not authorized in patients <18 years old due to its
effect on bone and cartilage growth.
Nirmatrelvir/Ritonavir
Nirmatrelvir
inhibits the SARS-CoV-2 protein that helps with the cessation of viral
replication while Ritonavir slows down Nirmatrelvir's breakdown for it to
remain in the body for longer periods at higher concentrations. Nirmatrelvir
must be co-administered with Ritonavir.
This
combination is recommended by the WHO in patients with non-severe COVID-19 at the
highest risk of hospitalization. It is approved by the US FDA for the treatment
of mild to moderate COVID-19 in adults who have positive SARS-CoV-2 test
results and who are at risk of progressing to severe COVID-19, including
hospitalization or death. The use of Nirmatrelvir/Ritonavir as a therapy option
that was granted EUA for the treatment of mild to moderate COVID-19 in children
aged ≥12 years old with positive SARS-CoV-2 test results and at risk of
progressing to severe disease, hospitalization, or death will continue to be
available in the US.
It
is recommended to initiate oral therapy as soon as the diagnosis of COVID-19 is
obtained and within 5 days of symptom onset. Three tablets (2 tablets of
Nirmatrelvir and 1 tablet of Ritonavir) are taken together twice a day for a
maximum of 5 days.
Corticosteroids
Corticosteroids
inhibit multiple inflammatory cytokines resulting in decreased edema, capillary
leakage, and migration of inflammatory cells, thereby globally suppressing the
inflammatory response. It is recommended by WHO for patients with severe or
critical COVID-19.
Dexamethasone
is recommended as the primary immunomodulator in all patients who require
high-flow cannula oxygen, noninvasive ventilation, mechanical ventilation, or
extracorporeal membrane oxygenation. Inhaled steroids are not recommended for
the treatment of COVID-19 pending the results of ongoing studies. Oral, inhaled,
or intravenous (IV) steroids are not recommended for prophylaxis or prevention
of COVID-19.
Disease-Modifying Anti-rheumatic
Drugs
Baricitinib
Baricitinib
is a Janus kinase inhibitor that was recently granted EUA by the US FDA that
can be given alone even without Remdesivir. It is indicated for the treatment
of adults and pediatric patients ≥2 years of age hospitalized with COVID-19
disease requiring supplemental oxygen, non-invasive or invasive mechanical
ventilation, or extracorporeal membrane oxygenation.
It
is recommended by WHO for patients with severe or critical COVID-19 in
combination with corticosteroids as an alternative to interleukin (IL)-6
receptor blockers. When Baricitinib is not available or not feasible to be
used, it is recommended to use Tofacitinib.
Monoclonal Antibodies
Regdanvimab
Regdanvimab
is a recombinant human IgG1 monoclonal antibody that binds to the receptor-binding
domain of the spike proteins of SARS-CoV-2. It is currently under rolling
review by the European Medicines Agency (EMA) and is given EUA by Indonesia's
National Agency of Drug and Food Control. It can be used for the treatment of
adult patients with confirmed COVID-19 who do not require supplemental oxygen
therapy and who are at high risk of progressing to severe COVID-19. It is given
by infusion (drip) into a vein.
Tocilizumab
Tocilizumab
is a recombinant humanized anti-human IL-6 receptor monoclonal antibody that
specifically binds sIL-6R and mIL-6R and inhibits signal transduction. It is granted
by the US FDA with EUA. WHO has recommended Tocilizumab or Sarilumab in
combination with corticosteroids for patients with severe or critical COVID-19.
It
is recommended in some countries to be used in patients admitted within 24
hours in the intensive care unit (ICU) and who require high-flow oxygen or more
intensive respiratory support. In some countries, it is recommended to be used
in combination with Dexamethasone in certain hospitalized patients who are in
rapid respiratory decompensation due to COVID-19. Avoid its use in patients who
are significantly immunocompromised or for outpatient treatment.
There
is still insufficient evidence to recommend the routine use of Tocilizumab or
other IL-6 inhibitors for severe COVID-19 patients suspected to be in cytokine
storm except in the context of a clinical trial or for compassionate use. When intravenous
Tocilizumab is not available or not feasible to use, it is recommended to use IV
Sarilumab.
Anticoagulants
It
is recommended that all patients who have been hospitalized should receive
standard prophylactic anticoagulation with low-molecular-weight Heparin if
without contraindications (eg active bleeding or severe thrombocytopenia).
Interferons
In
vitro, it has been shown that Interferon beta inhibits
SARS-CoV-2 replication. A large multinational trial using subcutaneous (SC) or IV
Interferon beta has shown no difference in the 28-day mortality compared with
standard care in patients hospitalized with COVID-19.
An
open-label, randomized trial was done in Hong Kong in adult patients with
confirmed SARS-CoV-2 with mild to moderate disease where they were given
Interferon beta-1b in the early onset of symptoms together with the combination
of Lopinavir/Ritonavir and Ribavirin and the treatment showed clinical
improvement of symptoms, shortening of viral shedding, and faster time to
hospital discharge. Future studies are warranted for a double antiviral therapy
with Interferon beta-1b as the backbone.
A
double-blind, placebo-controlled randomized trial was done in Toronto wherein
confirmed patients with SARS-CoV-2 with mild to moderate disease were given in
their early days of COVID-19 infection Peginterferon lambda and the trial
showed increased viral decline and an increased proportion of patients with viral
clearance at day 7 of treatment showing that Peginterferon lambda has potential
to prevent clinical deterioration. Interferons are for clinical trial use only.
Other Therapy
Oxygenation and Ventilation
It
is recommended to closely monitor patients receiving supplemental oxygen for
worsening respiratory status and that intubation should be done by an
experienced practitioner in a controlled setting. In patients with acute
hypoxemic respiratory failure despite conventional oxygen therapy, it is
recommended to give high-flow nasal cannula oxygen over noninvasive positive
pressure ventilation (NIPPV). If there is no indication for endotracheal
intubation, it is recommended to monitor the trial of NIPPV for adults with COVID-19
and acute hypoxemic respiratory failure if a high-flow nasal cannula is not
available.
For
patients with persistent hypoxemia after increasing supplemental oxygen and
endotracheal intubation is not otherwise indicated, it is recommended to
consider a trial of awake prone positioning to improve oxygenation. It is not
recommended to use awake prone positioning as a rescue therapy for refractory
hypoxemia to avoid intubation in patients who otherwise require intubation and
mechanical ventilation.
For
mechanically ventilated COVID-19 patients with acute respiratory distress
syndrome, it is recommended to use low tidal volume (VT 4 to 8 mL/kg of
predicted body weight) ventilation over higher tidal volumes (VT >8 mL/kg). The
recommended target plateau pressure is <30 cmH2O. It is
recommended to use a conservative fluid strategy over a liberal fluid strategy.
The routine use of inhaled nitric oxide is not recommended.
For
mechanically ventilated COVID-19 patients with moderate-severe acute
respiratory distress syndrome, it is recommended to use a higher PEEP strategy
over a lower PEEP strategy. PEEP is beneficial in patients with acute
respiratory distress syndrome because it prevents alveolar collapse, improves
oxygenation, and minimizes atelectotrauma, a source of ventilator-induced lung
injury.
For those who have refractory hypoxemia despite optimized ventilation,
it is recommended to use prone ventilation for 12 to 16 hours per day over no
prone ventilation.
Prevention (Revamp)
Hand Hygiene
The most effective
action to be taken to reduce the spread of pathogens and prevent infections is
hand hygiene. It is recommended to wash hands with soap and water whenever
possible, especially after coughing or sneezing; when caring for the sick; before,
during, and after preparing food; before eating; after toilet use; when hands
are visibly dirty; and after handling animals or animal waste.
Hand
sanitizers are used if handwashing is not possible and should contain at least
60% alcohol. They should be applied properly by rubbing the gel over all
surfaces of the hands and fingers until the hands are dry.
It
has been shown in the evidence from both the severe acute respiratory syndrome
(SARS) and COVID-19 epidemics that hand hygiene is very important to protect
healthcare workers from getting infected. Plain soap is effective at
inactivating enveloped viruses such as the COVID-19 virus due to the oily
surface membrane that is dissolved by soap thus killing the virus. The duration
of alcohol-based hand rubbing is 20 to 30 seconds while handwashing with soap and
water should be 40 to 60 seconds.
Face Masks
It
is recommended that a face mask be worn in public settings, like in public and
mass transportation, at events and gatherings, and anywhere that the person
will be around other people. It is used for either protection of healthy
persons or to prevent onward transmission.
A
medical face mask is recommended for healthcare workers in clinical settings, any
person who is feeling unwell including those with mild symptoms (ie muscle
aches, slight cough, sore throat, or fatigue), COVID-19-positive individuals or
those awaiting the result of COVID-19 test, those caring for suspected or
confirmed COVID-19 patients outside of health facilities, those aged ≥60 years
old, and those at any age who have underlying conditions including chronic
respiratory disease, cardiovascular disease, cancer, obesity, immunocompromised
status, and diabetes mellitus.
Non-medical
fabric masks are recommended for the general public under the age of 60 and who
do not have underlying health conditions.
A
fabric mask should have a good filtration rate, cover the nose and mouth
completely, snugly fit against the side of the face without gaps, and have ≥2
layers of washable, breathable fabric. The inner layer should be an absorbent
material, such as cotton; the middle layer should be a non-woven non-absorbent
material, such as polypropylene; and the outer layer should be a non-absorbent
material, such as polyester or polyester blend.
Medical
or surgical masks should consist of three layers of synthetic non-woven materials, be
configured to have filtration layers sandwiched in the middle, be available in
different thicknesses, and have various levels of fluid resistance and
filtration.
Respirators
(also known as filtering facepiece [FFP] respirators) are available at
different performance levels ie FFP2, FFP3, N95, and N99. They are used to
protect healthcare workers who provide care to COVID-19 patients in settings and
areas where aerosol-generating procedures are undertaken. Before using the respirator,
healthcare workers should be fit tested to ensure that they wear the correct
size.
Medical
masks and respirator masks have similar protection values. The hands should be
washed before putting on a mask and the mask should not be touched while
wearing it. In taking off the mask, handle only by the ear loops or ties then
fold the outside corners together and dispose properly. In washing the mask,
regular laundry detergent and the warmest appropriate water setting for the
cloth used to make the mask should be used then it is left in the dryer until
completely dry. Masks or respirators with exhalation valves are not recommended.
Social or Physical
Distancing
Social
or physical distancing is keeping a safe distance of at least 6 feet (about two arm’s
length) between people who are not living in the same household. It should be
practiced along with handwashing, wearing masks, and avoiding touching the face
with unwashed hands.
It
is important to have social distancing since the virus can be spread by people
who are asymptomatic but already have the disease. It is also important for the
protection of people who are at higher risk for severe illness from COVID-19.
It helps limit the chances of coming into contact with contaminated surfaces and
infected people outside the home.
Other Preventive
Measures
Other
preventive measures against COVID-19 disease include avoidance of touching the eyes,
nose, and mouth with unwashed hands, covering a cough or sneeze with a tissue
and throwing the tissue in the trash, and cleaning and disinfecting frequently
touched objects and surfaces.
Ventilation
Ventilation is the intentional introduction of fresh air into a space while
the stale air is removed to be able to maintain the quality of air in the space.
Ventilation is important to prevent the spread of the SARS-CoV-2 virus indoors
by reducing the airborne concentration of the virus that can come in contact with
the occupants. It is recommended to have an increased ventilation rate through
natural or mechanical means, preferably without recirculation of the air. Natural
ventilation should be considered by opening windows or doors if possible and
safe to do so. For mechanical systems, economizer modes of heating, ventilation,
and air conditioning (HVAC) operations should be used and potentially as high
as 100% in order to increase the percentage of outdoor air. Filters should be
cleaned regularly in cases of air recirculation.
Personal Protective
Equipment
Healthcare
personnel caring for patients with suspected or confirmed COVID-19 should have personal
protective equipment composed of the following:
- N95 respirator (or equivalent or higher-level respirator) or facemask (if a respirator is not available) should be worn before entry into the patient’s room; should be removed and disposed of properly upon exiting the patient’s room and hand hygiene should be done
- Eye protection using goggles or a face shield that covers the front and sides of the face should be worn before entering the patient’s room; it should be compatible with the respirator
- Gloves that are clean and non-sterile should be worn before entry into the patient’s room; should be removed and disposed of properly upon exiting the patient’s room and hand hygiene should be done; double gloving is not recommended
- An isolation gown that is clean should be worn before entry into the patient’s room; and should be removed and disposed of properly upon exiting the patient’s room and hand hygiene should be done; wearing >1 gown at a time is not recommended
Vaccines
As
of 12 August 2023, a total of 13,498,472,794 vaccine doses have been
administered worldwide as per WHO data. Vaccines can be given to the following:
- Adults and children ≥6 months old (please refer to local FDA
approval advisory of approved and EUA vaccines applicable by age)
- Vaccines with EUA approval can be administered to patients aged 16 to 18 years old and above with some vaccines indicated only for patients up to 59 years of age
- Patients who are planning to conceive
- Currently pregnant or who are lactating
- Immunocompromised or cancer patients would need clearance from their physicians
The
following COVID-19 vaccines are currently undergoing large-scale clinical
trials. Please refer to the local
drug regulatory agency for further information.
mRNA Vaccines
Example vaccines: Tozinameran
(approved by US FDA for patients ≥5 years of age while EUA was granted for
patients 6 months to 5 years old), mRNA-1273 (approved by US FDA for patients
≥18 years old while EUA was granted for patients 6 months to 17 years old).
This
vaccine is a nucleoside-modified RNA (mRNA) that encodes the spike glycoprotein
(S-protein) present on the surface of the SARS-CoV-2 virus that generates a sufficient
immunogenic response and induces vigorous binding antibody responses to both
full-length spike protein and receptor-binding domain. Both B cells and T cells
are involved in the immune response.
It
contains no live components thus there is no risk of the vaccine triggering the
disease. Immunogenicity is modifiable, efficacy is stable, and there is no
anti-vector immunity. The high immunogenicity of these vaccines may cause
increased reactogenicity that may result in more reports of local and systemic
adverse reactions. Ultra-cold storage is required with some of the mRNA
vaccines.
Protein Subunit Vaccines
Protein
subunit vaccines include harmless pieces (proteins) of the virus that cause
COVID-19 instead of the entire microbe. Once vaccinated, the immune system
recognizes that the proteins do not belong in the body and begins making
T-lymphocytes and antibodies. If the individual is re-infected in the future,
memory cells will recognize and fight the virus. Both B cells and T cells are
involved in the immune response.
These vaccines are suitable for patients who are immunocompromised. They
contain no live components thus there is no risk of the vaccine triggering the
disease. They are relatively stable; however, may require adjuvant and booster
shots.
Viral Vector Vaccines
Example
vaccines: Non-replicating viral vector (ChAdOx1-S), human adenovirus
(Ad26.COV2.S, JNJ-78436735) that were given EUA approval in some countries.
Viral
vector vaccines use a modified version of a different virus (the vector) to
induce both humoral and cellular immunity. Both B cells and T cells are
involved in the immune response triggered by the antigen. Those who have been
previously exposed to the human virus used as a vector may have a weaker immune
response to the vaccine due to previous immunity to the vector.
Inactivated Virus Vaccines
Example
vaccine: CoronaVac that was given EUA and full approval in some countries.
Inactivated
virus vaccines contain completely inactivated or killed pathogen which induces
protective antibodies against epitopes of hemagglutinin glycoprotein on the surface
of the virus. They tend to produce a weaker immune response than live
attenuated vaccines, thus adjuvants are required to provide an effective immune
response. Both T cells and B cells are involved in the immune response. They
are not suitable for those who are immunocompromised. They are relatively
sensitive to temperature; thus, it is necessary to have a careful storage.
Vaccine Booster
A
vaccine booster refers to another dose of a vaccine that was given to a patient
who gained enough protection after vaccination but with a waning immunity.
The
US FDA has granted EUA for Tozinameran and mRNA-1273 to be used as a single
booster dose that is to be given at least 6 months after completion of the
primary series in individuals >18 years of age. The US FDA EUA was granted
to Tozinameran to be used as a single booster dose in children 5 to 17 years
old at least 5 months after completion of primary vaccination. The US FDA has
also granted EUA for JNJ-78436735 to be used as a single booster dose to be
administered at least 2 months after completion of the single-dose primary
regimen to patients ≥18 years old. The US FDA EUA also states that the
available COVID-19 vaccines may be used as a heterologous (or "mix and
match") booster dose to all eligible individuals following the completion
of the primary regimen of a different COVID-19 vaccine.
The
WHO together with the Strategic Advisory Group of Experts (SAGE) on
Immunization and its COVID-19 Vaccines Working Group are still reviewing the
emerging evidence on the need for and timing of booster doses. Based on WHO,
the order of administering booster doses to different population groups should
follow that which has been laid out for the primary vaccination series; booster
doses should be prioritized for higher priority-use groups before lower
priority-use groups, unless there is adequate justification not to do so.
For
immunocompromised patients, WHO has recommended a third dose as well as a fourth
dose of mRNA COVID-19 vaccine due to significant risk of severe COVID-19 for
these patients when infected. In some countries, additional booster doses (ie fourth
dose to older adults and a fifth dose for immunocompromised persons) are
currently being offered. The limited available data suggests that for highest
risk groups, there is a benefit that supports the administration of an
additional booster dose.
Bivalent
"updated" COVID-19 vaccines contain the original virus strain that provides
broad protection against the COVID-19 virus and the omicron variant component
that will give better protection from COVID-19. EUA has been granted by the US
FDA to Tozinameran and mRNA-1273 for a single booster dose in children 6 months
to 4 years old and individuals 5 years of age and older at least 2 months after
completion of primary vaccination with three doses of monovalent COVID-19 vaccine.