key: cord-0704167-imincuo4
authors: Iqbal, Phool; Menik Arachchige, Suresh; Ali, Yousra; Qamar, Muhammad Sohaib; Jaouni, Hani Walid; Abdussalam, Ahmed Lutfe Mohamad
title: First case of concomitant cytomegalovirus (CMV) viremia in non‐immunocompromised COVID‐19 patient and ICU management strategy in Qatar with literature review
date: 2022-04-26
journal: Clin Case Rep
DOI: 10.1002/ccr3.5783
sha: b1fb74df033b903412957bd4a4ddbf9b4630920e
doc_id: 704167
cord_uid: imincuo4

COVID‐19 has created one of the world's worst pandemics and is associated with various life‐threatening complications and infections, possibly due to various internal and external host factors. Cytomegalovirus (CMV) coinfection is one of those infections. We present a challenging case of severe COVID‐19 infection managed in our ICU care facility with concomitant CMV infection. We aim to highlight the significance of early diagnosis and prompt management for a better outcome.

The World Health Organization has labeled the COVID-19 a global pandemic with over 150 million cases and more than 3.5 million recorded deaths worldwide as of May 2021. 1 Many countries have faced multiple outbreaks of this infection, with numerous reports of associated complications. The most common complications include cytokine storm leading to tissue damage, lung injury, venous/arterial thrombosis, stroke, and myocardial infarction. 2 Out of these complications, coinfection with life-threatening organisms such as tuberculosis, fungal infection, and other viruses such as Ebstein-Barr Virus (EBV) and cytomegalovirus (CMV), can also occur, which is usually associated with an immunocompromised state. 3, 4 Evidence on the management of these patients is lacking, and currently, there are no standard guidelines. We present such a case of concomitant CMV infection in COVID-19 patient who was critically ill and managed in ICU with a follow-up outcome.

A 50-year-old hypertensive Filipino gentleman presented to the emergency department (ED) with a 1-week dry cough and high-grade fever history. There was associated fatigue, arthralgias, and myalgias. On presentation to the ED, his vital signs showed tachypnea of 26 breaths/min with desaturating to 85% and requiring oxygen supplementation of 10-15L/min through a non-rebreather mask, sinus tachycardia at around110 beats/min, and blood pressure of around 150/100 mmHg-175/112 mmHg, In the light of ongoing COVID-19 pandemic, he was tested for COVID-19 PCR from nasopharyngeal swab and turned out to be positive. His chest XR revealed bilateral infiltrates predominantly in the lower zones, as shown in Figure 1 . Therefore, as there was tachycardia and tachypnea, a CT pulmonary angiogram (CTPA) was performed to rule out pulmonary embolism (PE). However, it was remarkable for bilateral ground-glass attenuation of the upper lobes and bilateral lower lobes segmental consolidation with bronchogram and no evidence of PE. His overall clinical picture suggested severe COVID-19 pneumonia leading to acute respiratory distress syndrome (ARDS). He was started on COVID-19 management protocol as per local guidelines. However, his clinical condition deteriorated on the 6th day of hospitalization. He had worsening tachypnea in the range of 40-45 breaths/min and had desaturation below 85% even after keeping on 100% Fio through continuous positive airway pressure (CPAP) ventilation. He did not improve and thus was intubated and put on mechanical ventilation. He had fever spikes above 39C, sepsis workup including blood, deep tracheal aspirate, fungal, and urine cultures was requested along with inflammatory markers such as C-reactive protein, procalcitonin, and interleukins to look for features of cytokine storm as well.

Meanwhile, he was covered empirically with broadspectrum antibiotics and antifungals, that is, meropenem, vancomycin, and anidulafungin. His sepsis workup was unremarkable and did not show any organism growth. His inflammatory markers were high, and he was continuously febrile with borderline mean arterial pressure of 60-65 mmhg, requiring inotropic support. He was clinically deteriorating, and his PaO 2 was not improving, despite proning him multiple times. His PF ratio remained below 100. CT scan of the thorax was done and did not show any PE or barotrauma but similar ground-glass opacities and infiltrates present in the initial CTPA as shown in Figure 2 . Therefore, he was placed on venovenous extracorporeal membrane oxygenation (V-V ECMO).

The patient had clinical improvement, and thus, it was decided to extubate the patient on the 25th day of his hospitalization. However, he had tachypnea, and difficulty breathing was re-intubated on the 31st day. Chest XR revealed new lung infiltrates in the left upper zone and raised suspicion of a new infection. Urgent bronchoscopy and subsequent bronchoalveolar lavage fluid cultures were sent, including CMV, EBV, adenovirus, fungal, and tuberculosis infection. Meanwhile, sepsis workup was repeated, including blood, urine, and other respiratory viruses PCR. Blood cultures grew Enterococcus faecalis, and tracheal aspirate showed Klebsiella pneumonia. He was given a course of antibiotics according to the sensitivities of the cultures. Still, on antibiotics, he was having mild-tomoderate fever.

Meanwhile, his BAL cultures came out to be positive for CMV along with blood cultures remarkable for CMV viremia and labeled as CMV pneumonitis. He was immediately commenced on IV Ganciclovir 375 mg BID and monitored CMV PCR as per Infectious disease (ID) specialist consultation. His overall clinical condition improved. The patient was tracheostomized and was de-cannulated off ECMO successfully. His GCS stabilized, and he could open his eyes and follow simple commands. According to the ID specialist's recommendation, the patient was followed with repeat CMV PCR to optimize the anti-viral therapy. The trend of CMV PCR viral load is shown in Figure 3 . On further follow-up, the patient remained stable for 2 months and continued physical rehabilitation therapy for critical care myopathy.

Since the beginning of the COVID-19 pandemic, the world has struggled to cope with the infection and its aftermath. There are many associated fatal complications, including myocardial infarction, stroke, pulmonary embolism, dysregulated immunity leading to serious life-threatening cytokine storm and risk of serious coinfections such as F I G U R E 1 Chest XR showing bilateral haziness and infiltrates, especially in the lower zones as marked with red arrows fungal infection of mucormycosis (aka black fungus), viral infections such as CMV, EBV, and tuberculosis as well that are associated with high mortality if not managed promptly. 5-7 CMV viremia is common in immunocompromised states, especially in solid organ transplant patients. 8 It is reported in the literature that an immunosuppressive state due to dysregulated immunity or certain immune modulators such as tocilizumab or steroids in COVID-19 patients can lead to CMV viremia, as seen in our case. [9] [10] [11] We have found few similar articles reported in the literature highlighting the significance of CMV infection management in COVID-19 patients with management approach and outcome as mentioned in Table 1 . 9, 10, [12] [13] [14] [15] [16] [17] [18] [19] [20] Our patient was not immunocompromised; however, one possibility that could have led to concomitant CMV infection would be dysregulated immunity due to underlying severe COVID-19 infection creating an immunocompromised state. 3, 6 Furthermore, immunosuppressive medications such as steroids and tocilizumab can also suppress immunity along with COVID-19-induced dysregulated immunity making a patient prone to lifethreatening infections. 3, 7, [9] [10] [11] Currently, there are no international standard management guidelines for such a challenging scenario of CMV infection in COVID-19 patients. However, in the literature, it is reported that early diagnosis of CMV viremia in highly suspected COVID-19 patients and management with anti-viral therapy, that is, ganciclovir, valganciclovir, and in some instances with Foscarnet, can be of proven benefit. The duration of the treatment is inconsistent among the studies. However, the patients have generally improved within 1-2 weeks of therapy. 12 Our patient was getting critically ill during the hospital stay and was managed at every point aggressively and promptly. Moreover, his management of CMV infection at the time of diagnosis optimized his further care, and he was stabilized.

COVID-19 patients are prone to life-threatening complications and infections, and CMV infection is one of the conditions that can lead to a fatal outcome. In our perspective, patient with severe COVID-19 disease that has partial or no response to supportive/local management or clinical deterioration needs to be investigated according to the hospital resources for superseded coinfections like CMV viremia as seen in our case with the initiation of empiric therapy to optimize the patient care for better outcome. 21 

We aim to highlight the significance of life-threatening coinfections like CMV viremia in COVID-19 patients. It depends on the patient clinical state, physician's assessment, and availability of hospital resources. Early 

COVID-19)

Late complications of COVID-19; a systematic review of current evidence

COVID-19 pneumonia, immunosuppression, and cytomegalovirus activation: a perspective

237 coinfection with COVID-19 and cytomegalovirus in kidney transplant recipients-a case series

The role of anticoagulation in post-COVID-19 concomitant stroke, myocardial infarction, and left ventricular thrombus: a case report

Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum

Coinfections in people with COVID-19: a systematic review and meta-analysis

Cytomegalovirus infections in solid organ transplantation: a review

Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19

Tocilizumab-induced cytomegalovirus colitis in a patient with COVID-19

Coinfection with coronavirus disease 2019, previously undiagnosed human immunodeficiency virus, Pneumocystis jirovecii pneumonia and cytomegalovirus pneumonitis, with possible immune reconstitution inflammatory syndrome

COVID-19 and cytomegalovirus co-infection: a challenging case of a critically Ill patient with gastrointestinal symptoms

A case of coinfection with SARS-COV-2 and cytomegalovirus in the Era of COVID-19

Cytomegalovirus enterocolitis secondary to experimental COVID-19 therapy

Epstein-Barr virus and cytomegalovirus reactivation in patients with COVID-19

Cytomegalovirus haemorrhagic colitis complicating COVID-19 in an immunocompetent critically ill patient: a case report

Cytomegalovirus proctitis as a complication of COVID-19 with immunosuppressive treatments

A misleading CMV myocarditis during the COVID-19 pandemic: case report

Convalescent plasma, cytomegalovirus infection, and persistent leukopenia in COVID-19 recovery phase: What is the link?

High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19

No time for pending confirmation of invasive fungal disease in critically ill COVID-19 patients-think empirical treatment

First case of concomitant cytomegalovirus (CMV) viremia in nonimmunocompromised COVID-19 patient and ICU management strategy in Qatar with literature review