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  Table of Contents    
Year : 2023  |  Volume : 66  |  Issue : 3  |  Page : 671-672
COVID-19 reactivating CMV or CMV complicating COVID-19: A need to conquer

1 Department of Lab Medicine, Sahara Hospital, Viraj Khand, Gomti Nagar, Lucknow, Uttar Pradesh, India
2 Department of Gastromedicine, Sahara Hospital, Viraj Khand, Gomti Nagar, Lucknow, Uttar Pradesh, India

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Date of Submission02-Mar-2022
Date of Decision02-May-2022
Date of Acceptance16-May-2022
Date of Web Publication03-Feb-2023

How to cite this article:
Siddiqui AH, Shukla A, Yadav D. COVID-19 reactivating CMV or CMV complicating COVID-19: A need to conquer. Indian J Pathol Microbiol 2023;66:671-2

How to cite this URL:
Siddiqui AH, Shukla A, Yadav D. COVID-19 reactivating CMV or CMV complicating COVID-19: A need to conquer. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Sep 27];66:671-2. Available from:

Dear Editor,

Cytomegalovirus (CMV) is present in an undetected form in 80% of the population. CMV disease is associated with inflammatory bowel disease (IBD), hematological malignancies, organ transplantation, and acquired immunodeficiency syndrome (AIDS).[1] It affects the eyes, lungs, liver, esophagus, stomach, and intestines. The most common clinical presentation of GI CMV disease is colitis, mimicking IBD.[2] Severe inflammation and vasculitis may lead to perforation and peritonitis of the bowel.[3] We describe a COVID-19 pneumonia case complicated by CMV.

A 68-year-old male presented with cough, cold, fever, and breathlessness for 10 days. The patient tested positive for COVID-19. After 15 days of admission, he became negative. He developed post-COVID pneumonia and was shifted to the non-COVID-19 ward for management. He developed bleed per rectum. Sigmoidoscopy revealed large ulcers with edematous friable mucosa associated with interspersed pale areas in the colon as shown in [Figure 1]a and [Figure 1]b). Sigmoid ulcer biopsy revealed inflammation, reactive changes, and inclusion of bodies typical of CMV [Figure 2]a and [Figure 2]b. Confirmation of CMV was done by reverse transcription-polymerase chain reaction (RT-PCR) for CMV DNA. A repeat COVID-19 RT PCR after a week of admission came positive. The patient was put on ganciclovir and shifted to the COVID-1919 ward again. He responded well and was discharged.
Figure 1: (a) Edematous friable mucosa with interspersed pale areas. (b) scattered hemorrhagic erosions and linear ulcerations

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Figure 2: (a) Cytomegalic stromal cells [hematoxylin and eosin (H and E) 20 ×]. (b) characteristic basophilic inclusion body [hematoxylin and eosin (H and E), 20 ×]

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The human immune system mounts a vigorous immune-defense targeting multiple immune-evasion genes encoded by this double-stranded DNA (dsDNA) β-herpes virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impairs cellular immunity by decreasing the activated T-cell markers (e.g. CD69), enhancing the expression of late activation markers such as CD25 and PD-1 in both CD4+ and CD8+ T-cells, reducing the lymphocyte number (lymphopenia), and rising proinflammatory cytokines and even cytokine storm.[4],[5]

Several publications have indicated that a dysfunctional immune response is associated with the severity of COVID-1919 and CMV disease or reactivation. There can be two scenarios associated with the present case. It could be a previous CMV infection leading to SARS-CoV-2 infection requiring hospitalization or SARS-CoV-2 infection leading to reactivation of CMV.

Repeated exposure to CMV antigen leads to depletion of naïve T-cell pool. This leads to a decreased immune response to other antigens including SARS-CoV-2. Chronic CMV infection and an impaired immune response predispose to COVID-19.[6]

SARS-CoV-2 infection causes strong activation of the innate immune system and inflammation of organs like the bowel and lungs. COVID-19 leads to severe lymphocytopenia and impaired cellular immunity. Depletion and exhaustion of functional T-cells and CD8+ T-cells lead to the reactivation of CMV. Studies have demonstrated a 27% CMV infection and a 31% reactivation rate in immunocompetent critically ill patients. Both are thought to suppress T-cells and NK cells, activate macrophages, and neutrophils which has detrimental effects.[6]

SARS-CoV-2 attaches to angiotensin-converting enzyme-2 (ACE-2) receptor present in the GI tract. Once the virus attaches itself to gut mucosa and epithelium, it leads to intestinal paralytic ileus, ischemia, and necrosis of the small intestine and colon. The CMV virus trapped in the GI tract can then be activated and may lead to hemorrhagic colitis.

The question which needs to be answered is whether CMV present in the latent phase led to the depletion of protective immunologic cells hence COVID-19 disease or COVID-19 infection led to the depletion of cells leading to infection or reactivation of CMV disease.

Our study also emphasizes the need of finding the prevalence of CMV infection among critically ill patients admitted to intensive care units (ICUs). CMV co-infection has been related to an increase in mortality. Timely detection and treatment of CMV treatment can help in reducing mortality and morbidity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Kumar M, Nizam MB, Mugunthan M. Seroprevalence of cytomegalovirus infection in antenatal women in a Tertiary Care Center in Western India. J Mar Med Soc 2017;19:51-4.  Back to cited text no. 1
  [Full text]  
Zhang LJ, Hanff P, Rutherford C, Churchill WH, Crumpacker CS. Detection of human cytomegalovirus DNA, RNA, and antibody in normal donor blood. J Infect Dis 1995;171:1002-6.  Back to cited text no. 2
La Rosa C, Diamond DJ. The immune response to human CMV. Future Virol 2012;7:279-93.  Back to cited text no. 3
Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: Addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther 2020;5:84.  Back to cited text no. 4
Van Duin D, Miranda C, Husni E. Cytomegalovirus viremia, pneumonitis, and tocilizumab therapy. Emerg Infect Dis 2011;17:754-6.  Back to cited text no. 5
Söderberg-Nauclér C. Does reactivation of cytomegalovirus contribute to severe COVID-19 disease? Immun Ageing 2021;18:12.  Back to cited text no. 6

Correspondence Address:
Areena Hoda Siddiqui
Department of Lab Medicine, Sahara Hospital, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_211_22

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