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\begin{document}

\title{First case of concomitant cytomegalovirus (CMV) viremia in
non-immunocompromised COVID 19 patient and ICU management strategy in
Qatar with literature review.}



\author[1]{Phool Iqbal}%
\author[2]{Suresh Menik Arachchige}%
\author[2]{Yousra Ali}%
\author[3]{Muhammad Sohaib Qamar}%
\author[2]{Hani Jaouni}%
\author[2]{Ahmed  Abdussalam }%
\affil[1]{Hamad Medical Corporation}%
\affil[2]{Hamad General Hospital}%
\affil[3]{Ozarks Medical Center}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
COVID 19 has created one of the world's worst pandemics and is
associated with various life-threatening complications, such as
Cytomegalovirus (CMV) co-infection. We present a life-threatening CMV
viremia co-infection in a none-immunocompromised COVID 19 patient to
highlight our management approach and a comprehensive literature review.%
\end{abstract}%



\sloppy


\textbf{Title:} First case of concomitant cytomegalovirus (CMV) viremia
in non-immunocompromised COVID 19 patient and ICU management strategy in
Qatar with literature review.

\textbf{Author Information:}

Phool Iqbal, MD, MBBS

Medical Intensive Care Department, Hamad Medical Corporation, Doha,
Qatar

dr.phooliqbal89@gmail.com

Suresh Menik Arachchige, MD

Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar

nalakamenik@live.com

Yousra Ali, MBBS

Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar

yali4@hamad.qa

Muhammad Sohaib Qamar, MD

Department of Medicine, Ozarks Medical Center, West Plains, MO, USA

mu.sohaibqamar@gmail.com

Hani Walid Jaouni, MD

Senior consultant Critical Care and Pulmonology department

Hamad Medical Corporation

HJaouni@hamad.qa

Ahmed Lutfe Mohamad Abdussalam, MD

Senior Critical Care Consultant Hamad General Hospital

Assistant Professor of Clinical Medicine, Weill Cornell Medicine Qatar

Medical Intensive Care Department, Doha, Qatar

aabdussalam@hamad.qa

\textbf{Key Clinical Message:}

This case highlights the significance of life-threatening co-infections
like CMV viremia in COVID 19 patients. It is important to be aware and
to investigate patients that are deteriorating for CMV viremia.

\textbf{Abstract:}

COVID 19 has created one of the world's worst pandemics and is
associated with various life-threatening complications, such as
Cytomegalovirus (CMV) co-infection. We present a life-threatening CMV
viremia co-infection in a none-immunocompromised COVID 19 patient to
highlight our management approach and a comprehensive literature review.

\textbf{Keywords:}

COVID-19, Coinfection, SARS-CoV-2, Cytomegalovirus

\textbf{Introduction:}

The World Health Organization has labelled the COVID-19 as a global
pandemic with over 150 million cases and more than 3.5 million recorded
deaths worldwide by the end of May 2021 {[}1{]}. Most countries have
faced multiple outbreaks of infection. Since the beginning of the
pandemic, there have been reports of numerous short-term and long-term
complications of covid-19. Of these, the most common ones include lung
injury, venous/arterial thrombosis, strokes, and myocardial infarctions
{[}2{]}. One of the most fatal complications include coinfection with
cytomegalovirus (CMV) and is mostly seen in patients with
immunosuppression as well {[}3,4{]}. There is little evidence on the
management of such patients. Given the novelty of these presentations,
no official guidelines have been established as of this date. In this
paper, we will present such a case. We will also present a thorough
literature search on the published data and present a possible clinical
approach to such patients.

\textbf{Case Summary:}

A 50-year-old hypertensive Filipino gentleman presented to the emergency
department (ED) with a one-week history of dry cough associated with
high-grade fever, fatigue, and myalgias. His vital signs showed
tachypnea around 22-26/min, tachycardia with a heart rate of
103-110/min, a blood pressure of around 175/112 mmHg, and desaturation
requiring 10l/min non-re-breather mask (NRM) to maintain o2 saturation
of around 86-88\%. He was tested positive for COVID-19 PCR from a
nasopharyngeal swab. His chest XR revealed bilateral infiltrates
predominantly in the lower zones (Figure 1). CT pulmonary angiogram
(CTPA) ruled out PE but showed bilateral ground-glass attenuation of the
upper lobes, and bilateral lower lobes segmental consolidations with
bronchogram. His overall clinical picture was suggestive of severe
COVID-19 pneumonia leading to acute respiratory distress syndrome
(ARDS). He was being treated based on local guidelines however his
condition deteriorated on the 6\textsuperscript{th} day of hospital
stay, with an increase in respiratory distress. He was having tachypnea
at around 40/min and was kept on non-invasive ventilation with
continuous positive airway pressure (CPAP) ventilation. He was shifted
to an ICU facility. He did not improve and was intubated and
mechanically ventilated on the 8\textsuperscript{th} day of his
admission. He was spiking fever and there was a rise in his inflammatory
markers concerning for a cytokine storm. Septic workup did not reveal
any microorganism growth or any source of infection. However he was
started on broad-spectrum anti-microbial drugs to cover any superseded
infection in severe COVID 19 patient .i.e. Meropenem, Vancomycin and
anidulafungin as per the recommendations of the infectious disease (ID)
specialists. His Pao2 was not improving, even after proning him multiple
times and giving him inhaled nitric oxide. Therefore, the decision to
commence the patient on veno-venous extracorporeal membrane oxygenation
(V-V ECMO) was made on the 16\textsuperscript{th} day of his admission.
CT thorax did not reveal any pulmonary embolism or barotrauma. However,
it redemonstrated the bilateral ground-glass opacities (Figure 2). The
patient's hospital course improved initially, and he was extubated on
the 25\textsuperscript{th} day of his admission and antibiotics were
ultimately stopped after the completion of their course.

On the 31\textsuperscript{st} day of admission, he was re-intubated due
to tachypnea and abnormal paradoxical breathing pattern. Initial chest
XR showed new lung infiltrates in the left upper zone. Bronchoscopy and
subsequent bronchoalveolar lavage fluid cultures were negative. Blood
cultures grew Enterococcus faecalis and sputum cultures grew Klebsiella
pneumonia. He was given a course of antibiotics according to the
sensitivities of the cultures. On the 39\textsuperscript{th} day of
admission, the patient was tracheostomized due to a prolonged course on
mechanical ventilation. The patient had fluctuations in his GCS,
drowsiness, intermittent fever spikes, rise in inflammatory markers and
was difficult to wean off from high oxygen settings. Septic workup was
repeated including blood cultures, urine culture, TB work up, tracheal
aspirate cultures, BAL fluid cultures and respiratory viruses including
CMV, EBV and adenovirus PCR. His urine and BAL cultures grew Candida
Albicans sensitive to Fluconazole. Furthermore, the BAL cultures and
blood cultures were positive for CMV. He was started on Ganciclovir with
weekly CMV PCR. His condition improved and was de-cannulated off ECMO.
His GCS stabilized and he was able to open his eyes and follow simple
commands. The patient was then followed with repeat CMV PCR viral counts
to optimize the anti-viral therapies according to the ID specialists.
The trend of CMV PCR viral load is shown in figure 3. On follow up, the
patient in under physical and occupational therapists to help with
critical care myopathy.

\textbf{Discussion:}

Since the beginning of the COVID 19 pandemic, the world is struggling to
cope up with the infection and its aftermath. There are many associated
complications and co-infections. Some of these include myocardial
infarction, stroke, pulmonary embolism, various viruses, and fungi
co-infection like CMV, EBV and currently mucormycosis (also known as
black fungus) is also seen in many cases with high mortality rates
{[}5,6,7{]}. CMV viremia is common in the immunocompromised state
especially in solid organ transplant patients {[}8{]}. However, an
immunosuppressive state due to dysregulated immunity or certain immune
modulators like Tocilizumab or steroids, in COVID 19 patients, can lead
to CMV viremia as seen in our case and in the literature as well
{[}9,10,11{]}. We performed a literature review of articles on Google
Scholar using advance search option with following keywords in title
``allintitle: COVID 19 and cytomegalovirus and Pubmed search strategy
with following keywords respectively ((((cytomegalovirus{[}Title{]}) OR
(CMV{[}Title{]}))) AND ((((COVID 19{[}Title{]}) OR (SARS COV
2{[}Title{]})) OR (coronavirus disease{[}Title{]})))). We managed to
find approximately 40 articles on CMV viremia in COVID 19 patients. Upon
screening, a total of 11 articles of severe COVID 19 infection that did
not have any underlying immunosuppressive state or malignancy were
selected (Table 1) {[}12,13,14,15,16,17,18,19,20,21,22{]}, in order to
correlate with the management strategy in our patient.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\textbf{DOI} & \textbf{Type of Study} & \textbf{Age (yrs)} &
\textbf{Comorbid conditions} & \textbf{COVID 19 severity} &
\textbf{COVID 19 treatment} & \textbf{CMV treatment} &
\textbf{Outcome}\tabularnewline
\midrule
\endhead
10.12890/2020\_001911 & Case Report & 62 & None & Severe ARDS &
Vasoactive drugs, corticosteroids, proning and ECMO & Ganciclovir &
Complete recovery and discharge\tabularnewline
10.1136/ bmjgast-2020-000556 & Case Report & 45-65 & None & Severe ARDS
& Remdesivir, Convalescent plasma, systemic hydrocortisone, tocilizumab
and ECMO & Ganciclovir, Foscarnet for persistent symptoms after
excluding drug resistance. & Improved and discharged to inpatient
skilled nursing facility on TPN and supplemental enteral
nutrition.\tabularnewline
10.12890/2020\_001652 & Case Report & 92 & Diabetes Mellitus and
Hypertension & Severe ARDS & Lopinavir/ritonavir and hydroxychloroquine
& None & Patient passed away from severe respiratory
failure\tabularnewline
10.1016/j.idcr.2020.e00962 & Case Report & 68 & Hypertension and
Glaucoma & Severe ARDS & Hydroxychloroquine, ECMO, tocilizumab and
Remdesivir & Intravenous ganciclovir & Not mentioned\tabularnewline
10.21203/rs.3.rs-52829/v1 & Observational Study & 60s & None & Severe
ARDS & Steroids and ECMO & NA & Not mentioned\tabularnewline
10.11604/pamj.2020.36.167.23922 & Case Report & 37 & NA & NA & NA & None
& Patient back to his baseline at 2 weeks follow up.\tabularnewline
10.4103/jpgm.JPGM\_1168\_20 & Case Report & 75 & Hypertension & Severe
ARS & Methylprednisolone, hydroxychloroquine, azithromycin, Remdesivir
and convalescent plasma. & Intravenous ganciclovir & Clinical
improvement\tabularnewline
10.1016/j.idnow.2021.01.005 & Retrospective Study & Median age 56 &
Hypertension (47\%), Diabetes Mellitus (32\%), Diffuse lung disease
(38\%) & Moderate to Severe & Lopinavir--Ritonavir, Interferon,
Remdesivir, Hydroxychloroquine, Tocilizumab and Corticosteroid &
Ganciclovir in 2 cases, Valganciclovir in 1 case & Pts with CMV viremia
were treated successfully with clinical improvement.\tabularnewline
10.1002/ccr3.3487 & Case Report & 42 & None & Severe ARDS & Tocilizumab,
hydroxychloroquine, antibiotics, antifungals, and methylprednisolone &
Ganciclovir & Had left hemicolectomy, was discharged to rehab
center.\tabularnewline
10.1002/ccr3.3600 & Case Report & 71 & Post Tuberculosis aspergilloma &
Severe covid pneumonia & Hydrocortisone & Ganciclovir & Was discharged
from the ICU\tabularnewline
10.1016/j.idcr.2021.e01111 & Case Report & 75 & Diabetes Mellitus and
Overweight (BMI 26.2) & Severe COVID 19 infection & dexamethasone,
ceftriaxone, spiramycin, oral lopinavir/ritonavir and anakinra & oral
valganciclovir & Underwent recto sigmoidoscopy\tabularnewline
\bottomrule
\end{longtable}

The table not only highlights the risks of getting severe CMV viremia
but also shows the management strategy and their outcomes. Our patient
was not immunocompromised, however due to severe COVID 19 infection
leading to dysregulated immunity and further management with steroids
and Tocilizumab leading to immunosuppressive state might have
contributed to CMV viremia. This concern needs a standard and effective
management strategy. Currently, there are no recommended guidelines for
initiating empiric anti-fungal therapy in CMV viremia in COVID 19
patients. From the literature, CMV viremia in covid-19 patients have
being treated with predominantly IV ganciclovir, in some cases
valganciclovir and in one case with foscarnet. However, the duration of
the treatment is not clear. Patients have improved with days to weeks
{[}12{]}. In our perspective, patient with severe COVID 19 disease that
have delayed recovery, partial or no response to supportive/local
management, must be investigated for superseded co-infections and
reactivations of infections like CMV viremia with initiation of empiric
therapy {[}23{]}.

\textbf{Conclusion:}

Through our case, we aim to highlight the significance of a life
threatening co-infections like CMV viremia in COVID 19 patients. The
management strategy depends on the clinical state of the patient and
availability of resources. However, prompt investigation in critically
ill COVID 19 patients that do not respond to treatment, must be done to
avoid fatal complications and death.

\textbf{Authors' Contribution:}

Drs. Suresh Menik Arachchige, Phool Iqbal and Yousra Ali were equally
involved with the litreture search, writing, and editing the paper.

Drs. Ahmed Abdussalam, Hani Jaouni and Muhammad Qamar were involved with
editing the paper and proving guidance.

\textbf{Ethical Disclosure:}

This manuscript has not been published and is not under consideration
for publication elsewhere. We have no conflicts of interest to disclose.
All authors have reviewed and agreed to the content present in this
Article.

\textbf{Consent:}

Written informed consent was obtained from the patient for publication
of this case report. A copy of the written consent is available for
review by the Editor-in-Chief of

this journal upon request.

\textbf{Acknowledgements:}

Funded by Qatar National Library.

\emph{References:}

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