CONTINUATION

Pathophysiology
Spike surface glycoprotein of the virus binds to the host via receptor binding domains of
the angiotensin converting enzyme 2 (ACE2), which is most abundant in type II alveolar
cells (J Virol 2020;94:e00127-20)
After a SARS-CoV-2 attaches to a target cell, the virion releases RNA into the cell,
initiating replication of the virus which further disseminates to infect more cells (Cell
2020 Mar 4 [Epub ahead of print])
SARS-CoV-2 produces several virulence factors that promote shedding of new virions
from host cells and inhibit immune response
Incubation period
● The exact incubation period is not known. It is presumed to be between 2 to 14 days after
● exposure, with most cases occurring within 5 days after exposure [8, 9, and 10].
● The spectrum of illness severity

● Most infections are self limiting. COVID-19 tends to cause more severe illness in elderly
● population or in patients with underlying medical problems. As per the report from
Chinese
● center for disease control and prevention that included approximately 44,500 confirmed
● Infections with an estimation of disease severity [11]
● • Mild illness was reported in 81% patients
● • Severe illness ( Hypoxemia, >50% lung involvement on imaging within 24 to 48
● hours) in 14%
● • Critical Disease (Respiratory failure, shock, multi-organ dysfunction syndrome) was
● reported in 5 percent
● • Overall case fatality rate was between 2.3 to 5%
● ge affected
● • Mostly middle aged (>30 years) and elderly.
● • Symptomatic infection in children appears to be uncommon, and when it occurs, it is
● usually mild [42]
Clinical Presentation
● In a study describing 1099 patients with COVID-19 pneumonia in Wuhan, the most
common clinical features at the onset of illness were: [41]
● •Fever in 88%
● •Fatigue in 38%
● •Dry cough in 67%
● •Myalgias in 14.9%
● •Dyspnea in 18.7%
● Pneumonia appears to be the most common and severe manifestation of infection. In this
group of patients breathing difficulty developed after a median of five days of illness.
Acute respiratory distress syndrome developed in 3.4% of patients.
Other symptoms
● •Headache
● •Sore throat
● •Rhinorrhea
● •Gastrointestinal symptoms
● About 80% of confirmed COVID-19 cases suffer from only mild to moderate disease and
● nearly 13% have severe disease (dyspnea, respiratory frequency
≥30/minute, blood
● oxygen saturation≤93%, PaO2/FiO2 ratio <300, and/or lung
infiltrates >50% of the lung
● field within 24-48 hours).
● Critical illness (respiratory failure, septic shock, and/or multiple organ
dysfunction/failure)
● is noted in only in less than 6% of cases.
Diagnosis
Nasopharyngeal swab is recommended for the specimen; oropharyngeal swab, sputum and
bronchoalveolar lavage may be used alternatively (CDC: Interim Guidelines for Collecting,
Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease 2019 (COVID-
19)
Definite diagnosis is based on detection of viral RNA by real time RT-PCR
Laboratory Meta analysis data:
Decreased albumin
High C reactive protein
High lactate dehydrogenase (LDH)
Lymphopenia
High erythrocyte sedimentation rate (ESR)
Radiology description
Ground glass opacities, crazy paving pattern and consolidation in bilateral lobes are common
findings
These CT findings peak 10 days after onset
LABORATORY FINDINGS
White Blood Cell Count
• White blood cell count can vary. It does not provide accurate information about
COVID-19. [40]
• Leukopenia, leukocytosis, and lymphopenia have been reported.
• Lymphopenia is more common, seen in more than 80% of patients [40]
• Mild thrombocytopenia is commonly seen. However thrombocytopenia is considered
as a poor prognostic sign. [40, 41]
INFLAMMATORY MARKERS
Serum Procalcitonin
• Serum procalcitonin is often normal at the time of admission; however it increases in
patients who require ICU care. In one study high D-Dimer and lymphopenia are asso
ciated with poor prognosis. [40, 41]
C - reactive protein (CRP)
• COVID-19 increases CRP. This seems to track with disease severity and prognosis.
In patients suffering from with severe respiratory failure with a normal CRP level an
alternative diagnosis should always be sought. [40, 41]
Patients who meet the criteria for suspect cases, as discussed above, should undergo
testing for SARS-CoV-2 and also respiratory pathogens. Respiratory specimen collection
from the upper and in particular lower respiratory tract should be performed under strict
airborne infection control precautions (25). Preferably these samples should be obtained as
early as symptom onset, since it yields higher virus concentrations.
SPECTRUM OF DISEASE:-
Severe Disease (14%)

• Respiratory rate > 30/min
• SPo2- <93%
• PaO2/FiO2 <300
• Lung infiltrates >50% within 24- 48 hours
Critically ill (5%)
• Respiratory failure (need of mechanical ventilation)
• Septic shock
• MODS
Is there a definitive therapy?
• No drug of choice
• Oxygen support
• Oxygen saturation to be maintained above 90%
• Conservative fluid management
• Give empirical antibiotics (As per institution based CAP guidelines)/ anti-viral (Osel
tamivir)
• High dependency / ICU care when needed.
Prognostic factors
Risks of acute respiratory distress syndrome development include age (> 65 years), underlying
diseases (diabetes mellitus) and secondary infection (JAMA Intern Med 2020 Mar 13 [Epub
ahead of print], Intensive Care Med 2020 Mar 3 [Epub ahead of print])
Risk factors for death among hospitalized Chinese patients, in order of strength of association
(Lancet 2020;395:1054)
Coronary heart disease (p < 0.0001)
Hypertension
Diabetes
Chronic kidney disease
Chronic obstructive lung disease (p = 0.047)
mechanism of HBOT oxygen therapy

The difference between HBOT oxygen therapy and normal pressure oxygen therapy is, in
general, the use of high pressure oxygen inhalation, which fully and substantially improves the
efficiency of oxygen transport
from the outside to the whole tissue cells. The mechanism of HBOT is to take advantage of the
physical characteristics of gas, to increase the
partial pressure of the oxygen in the environment through a large
amplitude, and to reduce the demand for oxygen exchange and
transportation in the body to achieve the best oxygen therapy effect.
Firstly, more elffectively than normal pressure oxygen inhalation to

overcome lung tissue inflammation.
The diffusion rate and distance of high pressure oxygen are several times that of normal pressure
oxygen, which overcome the gas exchange
obstacle caused by the thickening of the lung tissue inflammation.
And because of the higher solubility, the amount of oxygen dissolved in the
blood is several times that of atmospheric oxygen, which also further
overcomes the influence of the blood circulation gas ratio.
The application of HBOT to COVID-19 pneumonia/hypoxemia is supported by sound

physiology and Henry’s Law. Henry’s Law is the basis for the normal exchange of gases in
our lungs. It states that the concentration in a liquid (pulmonary blood) of an interfacing gas
(oxygen in the alveoli of the lungs) is proportional to the pressure of the interfacing gas.
Final oxygen uptake and binding to hemoglobin in pulmonary capillary red blood cells is
dependent on the diffusion of dissolved oxygen from alveolar wall→pulmonary
interstitium→capillary wall→blood plasma→red blood cell membrane→red blood cell
cytoplasm→hemoglobin. Interference with this process at any point results in decreased
oxygen-hemoglobin binding. In COVID-19 pneumonia patients the barrier to diffusion is
in the alveoli (inflammatory exudate-pneumonia) and inflamed interstitium. Standard
therapy is to exploit Henry’s Law by increasing the pressure of oxygen in the alveoli
(increasing the fractional inspired oxygen concentration): nasal cannula→venti-mask→non-
rebreather mask→endotracheal intubation. As the pneumonitis and hypoxemia progress
standard therapy cannot penetrate the diffusion barriers in the lungs because they are limited
by ambient pressure. In addition, it cannot treat the accumulating oxygen debt and intense
pulmonary and systemic inflammatory reaction. The options are to bypass the lungs with
extracorporeal membrane oxygenation (ECMO) or surmount the limits to dissolution of
oxygen in tissue and the barriers to oxygen diffusion by further exploiting Henry’s Law
with HBOT and increased pressure above ambient pressure.
Through Henry’s Law HBOT enhances multiple stages in the above process by increasing:
1) the dissolving of oxygen in the alveolar and inflammatory barrier
2) the diffusion rate of oxygen
3) the diffusion distance of oxygen
4) the dissolution of oxygen in blood plasma
5) the oxygen saturation of hemoglobin in red blood cells
6) the delivery of oxygen to the microcirculation and tissue.
The net result is a reversal of the downward spiral of COVID-19 patients.
The elevation of systemic levels of oxygen with HBOT has been traditionally misunderstood in
terms of respiratory metabolite effects with a transient hyperoxemia that dissipates once the
patient leaves the chamber. However, for 358 years, and especially in the modern era (1960 to
present), permanent and later trophic effects of HBOT have been documented with both single
and repetitive HBOT.
One of the mechanisms of action was recently elucidated as epigenetic modulation
through direct effects of hydrostatic pressure and hyperoxia of gene expression/suppression of
over 40% of the protein-coding genes in the human genome. The largest clusters of upregulated
genes are the growth, repair, cell signaling, and anti-inflammatory genes, and the largest clusters
of down-regulated genes are the pro-inflammatory genes and those that control programmed cell
death.
A single HBOT has been shown in multiple studies to have dramatic persisting effects on
disease pathophysiology, especially inflammation, its ubiquitous acute form, reperfusion injury
(e.g., carbon monoxide poisoning, necrotizing infection, resuscitation, and others), and extreme
form ARDS, and on reversing the lethal oxygen debt from cardiac arrest.
COVID-19 patients HBOT was likely treating:
● pulmonary and systemic hypoxia
● Inflammation
● Other pulmonary pathophysiologic targets
● lreversing oxygen debt
● Modulating gene expression both acutely and durably.

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Pathophysiology

● The spectrum of illness severity

Severe Disease (14%)

mechanism of HBOT oxygen therapy

Firstly, more elffectively than normal pressure oxygen inhalation to

The application of HBOT to COVID-19 pneumonia/hypoxemia is supported by sound

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