4.

4 Pneumonia 2– (COVID NOTES)

DR. Bermejo January 25, 2021
Elysian Trans by Nifras, Lianne Danielle
PEDIATRICS
Outline o Organ function: abnormal findings indicate organ damage
and possible progression to MODS
I. General Approach ▪ Renal function: monitor creatinine and urea
A. Laboratory Studies ▪ Hepatic function: monitor AST/ALT, GGT, bilirubin
▪ Cardiac enzymes: ↑ troponin indicates cardiac
B. Imaging
damage (See “Diagnostics” of acute coronary
C. Medical Therapy
syndrome.)
D. Experimental Drugs o Coagulation function: PT/INR, aPTT
E. Discontinuation of Isolation o D-dimer: elevated levels (particularly > 1 μg/L) at an early
stage indicate a poor prognosis
I. General Approach o Blood culture: initially 2 pairs
o If under undergoing propofol therapy: triglycerides every
• Administer O2 therapy via nasal canula: 1–6 L O2/min if SpO2 ≤
3 days
93%
- Careful with patients with COPD: a SpO2 of 90–93% is
Imaging
appropriate
⚫ All hospitalized patients should undergo initial and follow-up
• Provide supportive care:
imaging according to the clinical course.
- Adequate hydration, nutrition, and rest
- Fever management
o Chest x-ray: usually bilateral, peripheral opacities in
- Fluid-sparing resuscitation and electrolyte balance as needed
multiple lobes
• Evaluate and monitor: Vital signs, SpO2, laboratory studies, and
o Point-of-care ultrasound (POCUS): better results than
imaging should regularly be conducted to help guide management
chest x-ray and easily repeatable for reevaluation
and monitor progression.
▪ Thickened and irregular pleural lines
• Administer medical therapy as needed
▪ B lines as an early sign indicate a need for
o Recommended therapies may include remdesivir, intensifying care
dexamethasone, empiric antibiotic therapy, and/or
▪ Consolidation (both translobar or non-translobar)
anticoagulation indicates progression of the pulmonary disease
o Consider experimental drugs in the context of compassionate
▪ Should also screen for cardiomyopathy
use programs, research studies, and individual cases after
weighing the risks and benefits Chest CT: recommended for hospitalized patients
o
• Admit to ICU and administer ventilation if any of the following: ▪ Can initially be normal in up to 60% of hospitalized
o Signs of respiratory failure patients
o Dyspnea with hypoxemia ▪ CT findings are sometimes already present before
o Tachypnea (RR > 30/min) clinical manifestation.
• See also management sections of: ▪ Findings: generally bilateral, but a minority are
o Sepsis unilateral
o Pneumonia ▪ Ground glass opacities that can progress to solid
o Acute respiratory distress syndrome white consolidation in severe infection
o Airway management ▪ Inter- and/or intralobular septal thickening
o Mechanical ventilation ▪ Mixed “crazy-paving” pattern = combination of
ground-glass opacity with superimposed interlobular
Laboratory Studies septal thickening and/or intralobular septal thickening

⚫ Regular laboratory monitoring of hospitalized patients should Medical Therapy

include: ABG/VBG, CBC, electrolyte panel, inflammatory
markers (CRP, LDH, procalcitonin), organ function (creatinine,
urea nitrogen, urine volume, LFTs, cardiac enzymes),
coagulation tests, and D-dimer. Blood culture should also
initially be considered.
o Blood gas: to quickly monitor blood gas tension,
oxygen saturation, and pH gases
o CBC: Observe especially for ↓ WBC, ↓ lymphocytes,
and ↓ platelets. Advanced lymphocytopenia and
thrombocytopenia < 100.000/μL are signs of a severe
course.
◦ Leukopenia: ∼ 30% of cases
◦ Lymphocytopenia: ∼ 80% of cases
◦ Thrombocytopenia: ∼ 40% of cases
o Inflammatory markers: ↑ CRP, ↑ CK, ↑ LDH, and ↓
Albumin
▪ Procalcitonin (PCT) levels can be elevated in
patients with severe courses of the disease,
particularly if there is bacterial coinfection with
pneumonia and/or sepsis [60][110]
▪ ↑ Ferritin, ↑ IL-6
▪ See “Diagnostics” of sepsis for more information.
⚫ Currently recommended therapies (December 2020)
Recommendations vary based on the patient's condition and
oxygen supplementation needs. Based on the course of
disease, when indicated, consider administering remdesivir
early (To decrease viral replication) and corticosteroids later (to
counter cytokine storm).
⚫ Remdesivir
o Remdesivir was granted an Emergency Use
Authorization by the FDA (May 1, 2020), which
concluded that the possible benefits of the drug
currently outweigh the risks of its use based on the
following:
▪ Potential risk of a serious or life-threatening
course of disease in patients infected with SARS-
CoV-2
▪ No validated alternative treatment for COVID-19
available at this time
▪ Preliminary results from a randomized, controlled
clinical study in the US with about 1000 patients
with COVID-19 indicate a slightly faster time to
recovery in patients treated with remdesivir
compared to those treated with placebo.
o Based on current evidence, the NIH COVID-19
Treatment Guidelines Panel recommends using
remdesivir in the treatment of hospitalized adults and

1 of 4

pediatric patients (aged ≥ 12 years old and
weighing ≥ 40 kg) with COVID-19 who require
oxygen supplementation but do not need oxygen
supplementation through a high-flow device,
noninvasive ventilation, invasive mechanical
ventilation, or ECMO.
▪ Might be used in combination with
dexamethasone in patients who require oxygen
supplementation through a high-flow device or
noninvasive ventilation.
▪ Coadministration of chloroquine or
hydroxychloroquine is not recommended as
these drugs decrease the antiviral activity of
remdesivir.
▪ As of December 2020, there is not sufficient
data for recommending remdesivir for patients
who:
➢ Have mild to moderate COVID-19 (who do
not require supplemental oxygen)
➢ Require invasive mechanical ventilation or
ECMO
▪ The effectiveness and safety of remdesivir for
the treatment of children aged < 12 years and
weighing < 40 kg and pregnant women with
COVID-19 have not been evaluated. It may be
considered after weighing the risks and benefits.
⚫ Corticosteroids
o Based on results of a large randomized UK study in which
dexamethasone resulted in lower mortality for patients on
ventilators (reduced by ∼ 33%) and those requiring
oxygen (reduced by ∼ 20%), the NIH COVID-19
Treatment Guidelines Panel recommends using
dexamethasone in hospitalized patients who require:
▪ Mechanical ventilation or ECMO
▪ Oxygen supplementation through a high-flow
device or noninvasive ventilation
▪ Increasing amounts of oxygen supplementation
but not through a high-flow device
o Further studies
▪ Intravenous application
➢ Systemic corticosteroid therapy does not seem
to affect outcomes in mild courses of COVID-19.
➢ One study suggests faster recovery from severe
pneumonia in patients who have been treated
with low-dose methylprednisolone early in the
course of disease.
▪ Inhaled application: Withdrawing inhaled
corticosteroids in patients with preexisting health
conditions (e.g., asthma, COPD) who have previously
been treated with these drugs might increase the risk
of unfavorable outcomes.
⚫ Baricitinib
o Selective JAK1 and JAK2 inhibitor
o The FDA issued a EUA on November 19, 2020,
authorizing its use in combination with remdesivir in the
treatment of hospitalized adult and pediatric (aged ≥ 2
years) patients with COVID-19 who require oxygen
supplementation, mechanical ventilation, or ECMO.
o After reviewing the data, the NIH COVID-19 Treatment
Guidelines Panel issued the following recommendations
(as of December 2020):
▪ There is not enough data supporting the use of
baricitinib in combination with remdesivir in
patients who have no contraindications to the use
of corticosteroids. In cases where corticosteroids
are contraindicated, baricitinib can be used in
combination with remdesivir in nonintubated
patients who require supplemental oxygen.
▪ More studies are needed to clarify the use of
baricitinib in the treatment of patients with COVID-19.
4.04 Pneumonia 2
⚫ Anticoagulation: NIH COVID-19 Treatment Guidelines Panel
recommendations for preventing thrombotic events in patients
with COVID-19 include:
o Hospitalized nonpregnant adults with no findings
suggestive of a thromboembolic event should be treated
with prophylactic dose anticoagulation (e.g., with LMWH or
fondaparinux).
o Extended venous thromboembolism prophylaxis can be
considered after discharge in patients with a high risk of
thrombotic events (risk measurement should follow the
same recommendations used for patients without COVID)
and a low risk of bleeding.
▪ The indications for venous thromboembolism
prophylaxis in children with COVID-19 are the same as
for children without COVID-19.
▪ Hospitalized pregnant women with severe COVID-19
should be treated with prophylactic dose
anticoagulation unless there are contraindications for its
use.
➢ Patients with findings suggestive of a
thromboembolic event should be managed the
same as patients without COVID-19.
➢ There is currently no evidence supporting the use
of prophylactic anticoagulation therapy in
nonhospitalized patients.
Experimental Drugs
⚫ A variety of agents are being tested, and clinical studies are
being conducted. The use of these drugs can be considered in
the context of research studies, compassionate use programs,
and individual cases after weighing the risks and benefits.
⚫ RNA polymerase inhibitors and nucleotide analogs
o Baloxavir marboxil
o Favipiravir (approved in Japan)
⚫ Inhibition of adhesion and invasion
o Camostat (serine protease inhibitor, inhibits TMPRSS2)
o Inhibition of fusion
▪ Chloroquine and less toxic hydroxychloroquine ( ±
azithromycin)
➢ Currently (as of October 2020), there is no
evidence supporting the use of these drugs in the
treatment of patients with COVID-19.
➢ Also, there is no supporting evidence regarding the
efficacy to prevent COVID-19 when administered
as postexposure prophylaxis
➢ Drug shortages
▪ The dissemination of false information regarding the
efficacy of hydroxychloroquine to treat COVID-19 has
led to a surge in purchases and severe supply
shortages worldwide.
▪ Pose challenges to patients with rheumatic diseases
whose health depends on the availability of
hydroxychloroquine
▪ Umifenovir
⚫ Inhibition of protease
o Lopinavir/ritonavir
▪ As of October 2020, the US NIH recommends against
the use of lopinavir/ritonavir due to undesired
pharmacodynamics and no current evidence of
beneficial effects.
▪ Should only be administered in the context of clinical
trials
➢ Darunavir/ritonavir (possibly in combination with
umifenovir)
⚫ Inhibition of nuclear import: ivermectin
o Commonly used anti-parasitic drug
o Has been shown to reduce viral load in cell cultures
infected with SARS-CoV-2
⚫ Antibody therapy and biologicals
▪ SARS-CoV-2 spike protein receptor-binding domain
binders
2 of 4

➢ Recombinant human monoclonal antibodies that
bind to the SARS-CoV-2 spike protein receptor-
binding domain epitopes, blocking the entry of
SARS-CoV-2 into the host cells
o Bamlanivimab
▪ The FDA issued a EUA on November 10, 2020,
authorizing the use of bamlanivimab in the treatment
of patients with mild to moderate COVID-19 who are
at increased risk of disease progression and
hospitalization
▪ However, after reviewing the data, the NIH COVID-19
Treatment Guidelines Panel concluded that there is
currently (December 2020) not enough evidence
supporting the use of bamlanivimab in the
treatment of patients with mild to moderate
COVID-19
o Casirivimab and Imdevimab
▪ The FDA issued a EUA on November 21, 2020,
authorizing the use of casirivimab and imdevimab
combination in the treatment of patients with mild to
moderate COVID-19 who are at increased risk of
disease progression and hospitalization
▪ However, after reviewing the data, the NIH COVID-19
Treatment Guidelines Panel concluded that there is
currently (December 2020) not enough evidence
supporting the use of casirivimab and imdevimab
combination in the treatment of patients with mild
to moderate COVID-19
o IL-6 pathway inhibitors
▪ Increased levels of IL-6 are associated with more
severe courses of COVID-19. By inhibiting the
IL-6 pathway, these drugs are hypothesized to counter
immune response dysregulation
▪ Anti-IL-6 receptor monoclonal antibodies (Tocilizumab,
Sarilumab)
▪ Anti-IL-6 monoclonal antibody (siltuximab)
▪ Currently (as of October 2020), there is not enough
evidence demonstrating the efficacy of IL-6 pathway
inhibitors in the treatment of patients with COVID-19.
➢ Some studies demonstrated a decrease in
mortality and/or need for mechanical ventilation
➢ Others have not identified a clinical benefit.
▪ Recombinant ACE2 (rhACE2, APN01)
▪ Passive immunization through serum therapy
➢ The FDA issued a EUA on August 23, 2020, for
COVID-19 convalescent plasma to treat
hospitalized patients with COVID-19.
➢ However, as of September 2020, the NIH
COVID-19 Treatment Guidelines Panel states
that there is still not enough available clinical
evidence to support the use of COVID-19
convalescent plasma for the treatment of Covid-
19
⚫ Interactions between the drugs listed: numerous; this must
be kept in mind when considering administration (prescribing
information!) or use according to information provided by the
Liverpool Drug Interaction Group!
⚫ There are no proven benefits of hydroxychloroquine for
COVID-19 treatment, which is the main reason for the FDA
revoking the EUA of this usage. Hydroxychloroquine and other
drugs under investigation should only be used in COVID-19
treatment in the context of clinical studies. Otherwise, they
should be reserved for individuals who depend on these drugs
for other reasons (e.g., hydroxychloroquine for rheumatic
diseases).
⚫ When a drug is administered during the course of the disease
is likely a decisive factor. While drugs that inhibit the invasion
and replication of the virus (e.g., camostat, rhACE2) would
4.04 Pneumonia 2
have to be administered as early as possible, other
approaches, which aim to control immune response
dysregulation in severe courses (e.g., tocilizumab), could also
be effective in later stages of the disease!
⚫ No evidence that ACE inhibitors and NSAIDs aggravate
COVID-19
▪ Especially in March 2020, unconfirmed reports and
published hypotheses about the pathophysiology of COVID-
19 raised suspicions that RAAS antagonists (esp. ACE
inhibitors and angiotensin II receptor blockers), NSAIDs, and
thiazolidinediones may facilitate infection with and
exacerbate the course of COVID-19.
▪ Although these medications may increase ACE2 receptor
expression, there is currently (October 2020) no evidence
supporting the association between the treatment with these
agents and severe courses of the disease.
⚫ Regardless of COVID-19, NSAIDs may have nephrotoxic
and cardiotoxic effects in individuals with cardiovascular
and/or renal conditions.
Intensive Care
⚫ Indications: Admit to ICU and initiate intubation if any of the
following are present:
o Signs of respiratory failure
o Dyspnea with hypoxemia
o Tachypnea (RR > 30/min)
⚫ Airway management: Considering health-care workers have an
increased risk of developing COVID-19, especially during high-
risk procedures such as intubation, aerosol-generating
procedures should be avoided whenever possible!
o Endotracheal intubation: Rapid-sequence induction is
preferred, especially as it minimizes the spreading of
infectious aerosols.
o To avoid aerosolizing the virus, noninvasive ventilation,
high-flow oxygen therapy, bronchoscopy, and nebulizer
treatment should be avoided unless there is an absolute
indication.
▪ If NIPPV is indicated (e.g., COPD, asthma, DNI status):
attempt with a helmet (vs. face mask) interface
⚫ Mechanical breathing
o Management recommendations regarding ventilated
patients with COVID-19:
▪ Ventilation with lower tidal volumes (LTV) as with
ARDS: moderate tidal volume (6 mL/kg
▪ Plateau pressure < 30 cm H2O
▪ Permissive hypercapnia (target pH > 7.3)
▪ PEEP and FiO2 settings: adjust as needed according to
ARDSnet protocol
▪ See therapy of ARDS for more information.
⚫ The effects and indications of mechanical ventilation for patients
with COVID-19 are currently subject to discussion.
o High mortality rates among ventilated patients have been
reported and could be due to a variety of factors:
▪ Lung injury from COVID-19 might manifest differently
from typical ARDS, and adjustments in ventilation
management may be necessary.
▪ Lack of ventilation experts and personnel trained to
operate ventilation machines could contribute to worse
outcomes among severely ill patients.
▪ Strains on many health care systems worldwide, high
levels of stress among health care providers, and
insecurity about treatment strategies and management
for COVID-19 might affect the quality of care for some
patients:
➢ Physicians might favor drastic measures (e.g.,
intubation) over restrictive approaches (e.g.,
breathing masks) early in disease progression.
➢ Higher rates of intubated and ventilated patients
might result from concerns among health-care
3 of 4
 4.04 Pneumonia 2

professionals about contracting COVID-19

through potentially aerosol-generating methods
like nasal tubes and breathing masks.
▪ The effects of COVID-19 on the respiratory system
are not yet fully understood, prompting some
physicians to advise against changing established
protocols regarding ventilation management in
COVID-19 patients presenting with ARDS
▪ In patients with confirmed COVID-19 and relatively
mild signs of ARDS, high-flow nasal cannula therapy
could be considered initially. However, mechanical
ventilation might still be necessary at a later point in
the course of disease.

o Limited ventilator availability: High volumes of patients

with critical conditions due to COVID-19 have raised
concerns regarding ventilator shortages in hospitals
during the pandemic.
▪ Ventilator sharing: a controversial, off-label
procedure in response to ventilation capacity
shortages
➢ Pros and cons should be carefully considered in
the context of a specific situation.
➢ Some institutions are already experimenting with
sharing ventilators to compensate for short
supplies.
➢ The procedure is discouraged by some medical
societies.
➢ The FDA granted an Emergency Use
Authorization for ventilator expansion devices to
facilitate the treatment of up to four patients with
one ventilator
▪ New inventions: Mechanical devices have been
designed to compress a bag valve mask (BVM) and
serve as a temporary ventilator during emergencies and
times of ventilator shortages, specifically the COVID-19
pandemic.
➢ MIT E-Vent (Massachusetts Institute of
Technology Emergency Ventilator)
➢ AmboVent by the Israeli Air Force (IAF)
➢ Pandemic Ventilator Project

⚫ Extracorporeal blood purification therapy: can be used to

filter inflammatory cytokines from the blood of patients with
severe courses of COVID-19
o Use is based on the hypothesis that cytokine storms are
important in the etiology of severe courses
o The treatment is invasive, so it should only be
considered for patients with respiratory failure who are in
the ICU.
o A special filter, which can be used with standard
extracorporeal purification machines (e.g., for
hemodialysis), has been granted an Emergency Use
Authorization by the FDA (April 10, 2020).

Discontinuation of isolation & other transmission-based

precautions

⚫ CDC recommends to end home isolation according to a

strategy based on clinical criteria (December 2020)
o For patients with symptomatic COVID-19:
▪ 10 days after the onset of symptoms AND
▪ No fever for at least 24 hours without antipyretics
AND
▪ Respiratory symptoms have improved
o For patients with asymptomatic COVID-19: 10 days
have passed without illness since the date of the
positive COVID-19 test.
⚫ Currently (December 2020), the CDC and WHO do not
recommend discontinuing isolation according to test-based
strategies

4 of 4