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\begin{document}

\title{The second wave of desaturation in COVID-19}



\author[1]{Mohd Islam Alghizzawi}%
\author[1]{Fateen Ata}%
\author[1]{Zohaib Yousaf}%
\author[1]{Mousa Ahmad Alhiyari}%
\author[1]{Ammara Bint I Bilal}%
\author[1]{Abdelhaleem  Elhiday}%
\author[1]{Ahmad  Salih Abdulhadi}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\begin{abstract}
After a complete symptomatic recovery after COVID-19 pneumonia, the
second phase of desaturation is a new phenomenon that is being
increasingly observed. Two possible mechanisms behind it can be a
continued subclinical infection and lung fibrosis. We have presented a
case with the former mechanism, who responded well to steroids.%
\end{abstract}%



\sloppy


\textbf{Key Clinical Message:}

A second wave of dyspnea and desaturation is being observed post
COVID-19 pneumonia and ARDS. It may be secondary to an ongoing lung
inflammation or fibrosis after COVID-19 infection. Steroids may have a
role in the management of the inflammation.

\textbf{Introduction:}

In late 2019, a novel corona virus, severe acute respiratory syndrome
Coronavirus 2 (SARS-CoV-2), was identified in the human body and led to
a pandemic {[}1{]}. Understanding the spectrum of this disease, it's
prevention and optimal clinical management is the current focus of
physicians and researchers around the globe. Many drugs have been and
are being investigated for their role in the management of COVID-19
infection. Remdesevir has shown potential in decreasing hospital stay
among COVID-19 infected patients {[}2{]}. Dexamethasone has shown a
mortality benefit in severe COVID-19 {[}3{]}. However, the current
management of SARS-CoV-2 pneumonia and ARDS focuses mainly on providing
supportive measures {[}4{]}.

The clinical course in COVID-19 varies from asymptomatic disease to
fulminant ARDS {[}5{]}. There is anecdotal evidence about persisting
dyspnea following treatment of COVID-19. Post-COVID pulmonary fibrosis
is hypothesized to be one of the etiologies behind this phenomenon
{[}6{]}.Also, post- treatment; an asymptomatic patient may develop a
subclinical infectious process. This subclinical infection may lead to a
second phase of desaturation. There are currently no guidelines on the
treatment of this second phase of desaturation. We present a case
monitored the response of steroids in our patient who had desaturation
secondary to an ongoing residual subclinical inflammation after he was
treated for COVID-19 pneumonia. Our patient had an excellent response to
steroids; hence we postulate that steroids can be a potential treatment
for such patients.

\textbf{Case Presentation:}

A 53-year-old gentleman with a past medical history of diabetes
mellitus, hypertension, and dyslipidemia, presented to the hospital with
one day history of dyspnea. He was treated for COVID-19 pneumonia and
was discharged one day prior to his readmission. His initial
presentation was with dyspnea, fever, fatigue, and a dry cough.
Investigation revealed a positive SARS-CoV-2 reverse transcription
polymerase chain reaction (RT-PCR) with bilateral infiltrates on Chest
Xray (CXR) {[}Figure 1a{]}.

Initially he required 3-4 L of oxygen to maintain saturation, but the
requirement increased in the subsequent days and reached up to 13 Liters
of oxygen via non-rebreather (NRB) mask. He was treated with favipravir
and dexamethasone for 10 days, according to the local guidelines at the
time. The patient gradually improved, and his oxygen requirement
decreased. He was discharged from the hospital in an asymptomatic
condition, saturating 100 percent on room air. His repeated SARS-CoV-2
RT-PCR as negative.

One day after discharge, the patient presented with a new onset
shortness of breath at rest and exertion. He was requiring 2-3 Liters of
oxygen to maintain saturation (SPO\textsuperscript{2}) above 94 \%, and
was tachypneic (26 breaths per minute). He was afebrile and did not have
any other symptoms. Chest examination revealed bi-basal crackles, with
rest of the physical exam unremarkable.

A Chest Xray (CXR) was repeated and did not show significant changes
comparing to the previous one {[}Figure 1b{]}. A CT pulmonary
angiography showed no evidence of pulmonary embolism. However, it was
significant for extensive bilateral patchy areas of ground glass
opacities and patchy areas of consolidations with air bronchograms
{[}Figure 2{]}.

He was tested again for COIVD-19, but the RT-PCR result came negative,
ruling out a possibility of reinfection. The sepsis workup did not
reveal any bacterial growth (including Mycoplasma pneumonia, Legionella
pneumophila and Chlamydia pneumonia). Nasopharyngeal PCR for common
respiratory viruses (including Influenza, Parainfluenza, Respiratory
syncytial virus and Middle East respiratory syndrome coronavirus) were
negative. A bronchoscopy performed to rule out tuberculosis (TB),
eosinophilic pneumonia or pulmonary hemorrhage was unrevealing.

As the patient continued to have desaturation, a multidisciplinary team
decided to start a trail of 60 mg prednisolone for 2 weeks. He responded
very well, and oxygen requirement decreased. He was off oxygen at rest
in two days and was discharged with a follow-up in pulmonary clinic.

Repeated CXR after 2 weeks from discharge showed significant regression
on bilateral infiltrate {[}Figure 1c{]}. Pulmonary Function Test (PFT)
was done, which showed a restrictive pattern with decreased Diffusing
capacity for carbon monoxide (DLCO) {[}Figure 3{]}. A 6 minutes walking
test showed a vivid improvement compared to his previous condition where
was not able to complete more than 3 minutes of walking.

\textbf{Discussion:}

COVID-19 infection has a wide spectrum of clinical course and can
involve various organs. Lungs are the most common organs involved.
Presenting complains include a dry cough, fever, myalgias, headache,
dyspnea, sore throat, diarrhea, vomiting, ageusia and anosmia {[}7{]}.
Most cases of COVID-19 infection are mild to moderate, whereas around 20
\% progress to severe and critical illness. The long-term Respiratory
sequelae of COVID 19 infection remains unclear, and may depend on
disease presentation {[}8{]}.

The greater part of research related to SARS-CoV-2 focuses on the
management. To date, the treatment is largely supportive. Many drugs
have been and are being investigated for this purpose, including
hydroxychloroquine, Interleukin-6 pathway inhibitors such as
tocilizumab, convalescent plasma, remdesivir and dexamethasone {[}2, 3,
9-11{]}. Among all the tested treatment modalities, the most promising
results are from remdesivir and dexamethasone, as the preliminary
reports show a reduction in hospital stay from the former and a reduced
mortality by the latter.

The RECOVERY trial is investigating the role of dexamethasone in
SARS-CoV-2 infection. Initial results show a decreased 28-day mortality
in the treatment arm. However, this effect is seen only in the subset of
patients requiring invasive and non-invasive mechanical ventilation
{[}3{]}. Consequently, current guidelines recommend the use of
dexamethasone only in moderate to severely ill patients {[}12{]}.

In some patients, a second phase of dyspnea is seen after an interval
asymptomatic recovery phase in patients successfully treated for
COVID-19 pneumonia or ARDS. We propose two possible mechanisms behind
this, post-infection fibrotic changes in the lungs or a continued
subclinical infective process which becomes symptomatic again after some
time. Fibrotic lung changes are reported in survivors with COVID-19
pneumonia and abnormalities in lung function have been detected in
COVID-19 patients shortly after the discharge from the hospital {[}6,
13{]} . Our patient suffered from ongoing lung damage despite viral
clearance and symptomatic recovery. This resulted in chronic lung
changes as the pulmonary function test revealed a restrictive pattern
with decreased diffusion capacity.

Pulmonary fibrosis usually occurs secondary to dysregulated healing
process. Chronic inflammation can lead to fibrosis. The changes in the
cellular and molecular environment in the lung tissue secondary to viral
infection as in COVID are the key factors behind the fibrosis {[}14{]}.

The ongoing damage takes place in the tissues secondary to the
inflammation leading to an over expression of inflammatory cytokines,
including transforming growth factor-1 , tumor necrosis factor-a
(TNF-a), interleukin-1, and interleukin-6 (IL-6 ). This in turn
stimulates the proliferation of type 2 alveolar cell and increase in
fibroblast recruitment {[}15, 16{]}. Eventually, the cascade can lead to
an increase the production and deposition of extracellular matrix (ECM),
impairing gas exchange and hence leading to hypoxemia {[}16{]}.

The long-term reversible and irreversible respiratory sequelae of
COVID-19- remain obscure, as does the patient population at a high risk
to develop them. Our patient had an excellent recovery with steroids.
Authors are of the view that a large scale randomized controlled trial
is required to establish the efficacy of steroids in post-COVID-19
recurrent dyspnea.

\textbf{Conclusion:}

The second wave of desaturation after resolution of symptoms
post-COVID-19 treatment is a rare phenomenon. It can be secondary to an
ongoing subclinical infection or due to fibrosis. The role of steroids
is not studied in this scenario. Our patient had a dramatic response to
steroids indicating a possible role in reducing the post infection
inflammation. Larger studies are needed to investigate the management of
post-COVID-19 desaturation.

\textbf{Acknowledgements:}

None

\textbf{Author contributions}

\textbf{Conceptualization:} FA, AA

\textbf{Patient consent:} Mohd A

\textbf{Literature review:} FA, AB, ZY, Mohd A, Mousa A, AE, AA

\textbf{Manuscript writing:} FA, ZY, Mohd A

\textbf{Radiology part in writing and images:} AB

\textbf{Critical review and modifications:} FA\textbf{,} ZY, AE, AA

\textbf{Final review and approval:} FA, AB, ZY, Mohd A, Mousa A, AE, AA

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\textbf{Figures:}

\textbf{Figure 1.} CXR of patient (1a: at the time of COVID-19, showing
bilateral infiltrates, 1b: at the time of second admission, showing
similar changes, 1c: in follow-up clinic with improvement in
infiltrates).

\textbf{Figure 2.} CT pulmonary angiogram, showing post infection
changes

\textbf{Figure 3.} Pulmonary Function Test (PFT), revealing a
restrictive pattern with decreased Diffusing capacity for carbon
monoxide (DLCO).\selectlanguage{english}
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