Pulmonary cytomegalovirus infection: A case report and systematic review

Table 1 Summary of systematically reviewed clinical cases of cytomegalovirus pneumonia

Ref.	Age	Sex	Clinical findings	Immune status	Radiographic findings	Serology	Immunohistochemistry & biopsy	Treatment	Out-come
Luís et al[22], 2021	42	M	Fever, headache, odynophagia, bilateral otalgia	Immunocompetent	CXR – B/L infiltrates; Thoracic CT – B/L GGO	Blood – CMV PCR positive; BAL fluid – CMV PCR positive		Ganciclovir and valganciclovir	Recovery
Balakrishnan et al[23], 2022	41	M	Fever, cough, weight loss	Immunocompromised; chronic glomerulo- nephritis, IgA nephropathy; on immunosuppressive drugs	CXR – B/L infiltrates; Thoracic CT – B/L GGO, patchy consolidation, nodular opacities	Blood – CMV PCR positive; BAL fluid – CMV PCR positive		Valganciclovir	Recovery
Basinger et al[24], 2022	70	M	Rapid decline in general condition, resp. distress	Immunocompromised; a history of allogenic hematopoietic stem cell transplant	Rapidly progressive bilateral pulmonary nodules	Not done	Post mortem cytopatholog. Change, consistent with CMV infection, confirmed by IHC	Not initiated	Died
Gonçalves et al[2], 2018	29	M	Fever, headache, malaise, cough, thoracic pleuritic pain	Immunocompetent	Thoracic CT showed bilateral infiltrates	Blood – positive for CMV IgG and IgM; BAL – CMV PCR was positive		Ganciclovir and valganciclovir	Recovery
Wong et al[25], 2022	37	M	Fever, cough, dyspnea	Immunocompromised; X-linked agammaglobulinemia is a hereditary immune disorder		CMV positive		Antiviral and immune globulin therapy	Recovery
Gangemi et al[26], 2021	72	M	Non-healing buccal ulcer, fever, acute hypoxic respiratory failure, worsening odynophagia, weight loss	Immunocomromised; oropharyngeal Ca in remission	Chest X-ray – patchy opacities of B/L lung fields; Thoracic CT – bilateral upper and lower lobe consolidations, B/L pleural effusions	Positive for both CMV IgG and IgM		Ganciclovir and valganciclovir	Recovery
Patil et al[27], 2020	23	F	Worsening dyspnea, high grade fever, dry cough	Immunocompetent	Chest X-ray – mild bilateral interstitial infiltrates with small bilateral pleural effusions; CT chest - worsening of bilateral interstitial infiltrates	BAL CMV PCR and blood CMV PCR positive		Ganciclovir and valganciclovir	Recovery
Alyssa et al[28], 2017	63	F	Fever, hypotension, dyspnoea on exertion, hypoxemia, weakness	Immunocompromised; diagnosis of dermatomyositis - history of prolonged use of glucocorticoids and treatment with rituximab	CT chest - bilateral GGOs in a mosaic distribution and consolidations of B/L lower lobes	CMV DNA PCR quantitation in whole blood was positive and shell-vial culture for CMV positive		Ganciclovir and valganciclovir	Recovery
Fragkiadakis et al[29], 2018	36	F	Fever, respiratory distress	Immunocompromised; undergone multiple transfusions, and splenectomy was done for homozygous β-thalassemia	CT chest demonstrated pneumonitis	Serology and molecular blood testing reports – CMV infection and viremia		Ganciclovir	Recovery
Waqas et al[30], 2019	36	M	Fever, cough, malaise	Immunocompetent	CXR – B/L infiltrates	Diagnosed with CMV infection		Ganciclovir	Recovery
Xie et al[31], 2021	22	M	Fever, progressive dyspnea, dry cough	Immunocompromised; newly diagnosed HIV infection	Chest CT – extensive GGOs of bilateral lungs with multiple cavity lesions in the left upper lung	CMV quantitative PCR positive		Ganciclovir	Recovery
Al-Eyadhy et al[32], 2017	12	M	Tachycardia, tachypnea, fever, severe ARDS with multi-organ failure	Immunocompetent; CMV infection associated morbidity and mortality among immune-competent children	CXR and chest CT – ARDS features	CMV PCR positive in blood	HPE of lung biopsy CMV positive	Ganciclovir	Recovery
Reesi et al[33], 2014	3	M	Fever, dyspnea	Immunocompromised; acute lymphoblastic leukaemia on chemotherapy	CXR - pulmonary infiltrates; CT chest - diffuse GGOs of B/L lung fields, few pleural-based nodules	BAL CMV PCR was positive; CMV IgG and IgM positive		Ganciclovir and valganciclovir	Recovery
Cunha et al[34], 2008	64	M	“Flu-like illness”, fever, myalgias, progressive dyspnoea, and required mechanical ventilation	Immunocompetent; slowly improved over 14 d and was eventually extubated	Chest X-ray showed B/L interstitial markings that rapidly progressed over 24 h	Initially IgG, IgM and CMV PCR negative; 10 d later, IgG, IgM, and CMV PCR were positive	BAL cytology was negative for viral inclusions	Did not receive CMV antiviral therapy	Recovery
Demirkol et al[35], 2018	2	M	Respiratory distress, fever, multiple organ dysfunction secondary to sepsis	Immunocompetent; developed necrotizing pneumonia	Thoracic CT – features of necrotising pneumonia	Serological tests indicated that the patient had CMV reactivation	Excised lung tissue, features of CMV infection	Ganciclovir	Recovery
Margery et al[36], 2009	43	F	Fever, dyspnoea	Immunocompetent	Thoracic CT – diffuse GGOs	Anti-CMV IgM and PCR detection of viral DNA in serum		Not treated	Recovery
Bansal et al[37], 2012	45	F	Nausea and vomiting. CMV infection can present with only atypical symptoms in liver transplant patients	Immunocompromised; liver transplant due to anti- tubercular drug induced acute liver failure	CXR showed B/L infiltrates	Testing of CMV viral load showed a viral load of 9640 copies/mL		Ganciclovir	Recovery
Sunnetcioglu et al[38], 2016	24	M	Cough, fever dyspnoea, haemoptysis, shortness of breath, and was intubated	Immunocompromised; on immunesuppressive therapy for polyarteritis nodosa	Chest X-ray showed right-sided opacity in the middle and lower lung zones Thoracic CT showed B/L alveolar opacity	Positive test for serum CMV IgM antibodies		NA	NA
Liatsos et al[39], 2017	40	F	Acutely ill with fever, dry cough, and mild shortness of breath	Immunocompromised; β-thalassemia major with splenectomy, regularly transfused with packed and leukocyte-depleted red blood cells	Thoracic CT - B/L interstitial lung infiltrates and small nodules marked toward the lower lobes, with a few ground-glass areas and bilateral pulmonary effusions	Positive RT-PCR for CMV in both blood and BAL		Ganciclovir and valganciclovir	Recovery
Wickramasinghe et al[40], 2022	32	M	Headache, fever, cough, and shortness of breath. The patient was in respiratory distress, shifted to ICU and electively intubated	Immunocompromised; Tuberculosis meningitis	Chest X-ray showed left-sided consolidation. CT chest revealed lower lobe (left more than right) consolidation and nodules	Positive CMV IgM and negative IgG, suggesting acute infection		Antitubercular drugs and ganciclovir	Recovery
Barclay et al[41], 2011	38	F	Fever and non-specific symptoms & increasingly hypoxaemic	Immunocompetent	Thoracic HRCT showed diffuse multilobular ground glass appearance with peripheral nodular opacities	CMV IgM antibody was positive and CMV PCR was positive		Valganciclovir	Recovery
Coussement et al[42], 2016	64	F	Fever, cough, dyspnea, hypoxemia	Immunocompromised; bilateral lung transplant for chronic obstructive pulmonary disease	Thoracic CT demonstrated bilateral infiltrates; abdominal CT showed peri-colic infiltration compatible with a recurrence of diverticulitis	CMV VL observed both in blood and BAL samples; a diagnosis of CMV pneumonitis using BAL sample; a macrophage characteristic of CMV viral infection	Resected colon revealed HPE CMV colitis, viral inclusions, and positive immunohistochemistry	Ganciclovir	Recovery
Kanhere et al[43], 2014	3 1/2	M	Fever, respiratory distress, hepatosplenomegaly	Immunocompromised; hemophagocytic lymphohistiocytosis		CMV IgM serology was reactive in both infant and mother		Ganciclovir	Recovery
Suresh et al[44], 2013	7/12	M	Cough, dyspnoea, respiratory distress, progressive increase in oxygen requirement	Immunocompetent	Chest XR -prominent bronchovascular markings	CMV IgM serology was positive and CMV PCR based on BAL was also positive		Ganciclovir and valganciclovir	Recovery
Suresh et al[44], 2013, Case 2	3/12	F	Cough, dyspnoea, respiratory distress, progressive increase in oxygen requirement	Immunocompetent	CXR normal	CMV IgM blood was raised; BAL positive for CMV PCR		Ganciclovir and valganciclovir	Recovery
Yu et al[45], 2017	64	M	Acute respiratory failure with renal failure	Immunocompromised; diabetic; severe CMV pneumonia with slow resolution or persistent viremia on treatment	Chest X-ray -predominately right lung infiltrates; chest CT showed multiple consolidative patches with air bronchograms	Positive CMV PCR in blood and BAL	Lung biopsy was done. Inclusion bodies, positive for CMV IHC	Ganciclovir and valganciclovir	Died
Tollitt et al[46], 2016	71	F	Hemoptysis	Immunocompromised; antineutrophil cytoplasmic antibody-associated vasculitis; on therapy with cyclophosphamide, steroids, and plasma exchange	Pulmonary CMV disease mimics pulmonary disease associated with vasculitis on CXR	BAL demonstrated positivity for CMV DNA and serum CMV PCR positive		Ganciclovir and valganciclovir	Recovery
Vetter et al[47], 2010	70	F	Fever, nausea, dyspnea	Immunocompromised; immunosuppressive therapy with methotrexate and prednisone for large-vessel vasculitis	Chest X-ray showed no interstitial pneumonitis; chest and abdominal CT showed no signs of inflammation	CMV IgG and IgM antibodies positive; CMV PCR positive in BAL fluid		Ganciclovir	Recovery
Snape et al[48], 2011	28	F	Fever, cough tender sinuses, frontal headache	Immunecompetent	CXR showed consolidation of the middle and right upper lobe; Pulmonary CT angiography revealed no pulmonary embolus and patchy consolidation of B/L lungs	Positivity for CMV IgM		Valganciclovir	Recovery
Karakelides et al[49], 2003	47	M	Cough, hemoptysis, weight loss	Immunocompetent	CXR and chest CECT showed a 3.5-cm cavitary mass, upper lobe of left lung and mild left mediastinal and hilar adenopathy	Transbronchial biopsy - CMV inclusions	Wedge excision of left upper lung mass; HPE -nuclear & cytoplasmic inclusions of CMV	NR	Recovery
Shimada et al[50], 2004	27	F	Fever	Immunocompromised; on immunosuppressive treatment for viral-associated hemophagocytic syndrome	CXR and chest HRCT – diffuse small pulmonary nodules	CMV DNA PCR was positive on bronchoalveolar lavage cells; immunoassay pp65 CMV antigen positive	Lung biopsy inclusion-bearing cells for CMV	Gancyclovir	Recovery
Simsir et al[51], 2001	43	M	Malaise, fever, pleuritic chest pain, epigastric pain, diarrhea, nausea, vomiting	Immunocompromised; underwent renal transplant secondary to diabetic nephropathy	CXR showed a nodule in the upper lobe of the right lung; chest CT revealed bilateral smaller pulmonary nodules	CMV antigen test was positive, with negative CMV IgG	CMV was established by fine-needle aspiration biopsy of the lung nodule	Gancyclovir	Recovery
Abbey et al[52], 2014	51	M	Fever, dry, cough, dyspnoea, general malaise	Immunocompromised; Crohn’s disease on azathioprine; also had mild pancreatic insufficiency and bile salt malabsorption	CXR showed bilateral infiltrates in middle and lower zones; chest CT showed B/L small pleural effusions and B/L basal lung consolidation	CMV IgM positive, acute CMV infection		Ganciclovir and valganciclovir	Recovery
Belin et al[53], 2003	47	F	Shortness of breath, fever, stomatitis, genital ulcerations, burning sensations	Immunocompromised; severe rheumatoid arthritis, on prednisolone, methotrexate, and cyclosporine	CXR showed interstitial infiltrates in both lung bases	BAL showed CMV mRNA		Ganciclovir	Recovery
Kaşifoğlu et al[54], 2006	21	F	Polyarthralgias, fatigue, fever, muscle weakness, non-productive cough, dyspnea	Immunocompromised; dermatomyo-sitis, treated with azathioprine, prednisolone, and cyclosporine	Chest XR showed bilateral interstitial infiltration; chest HRCT - bilaterally ill-defined multifocal GGOs	Positivity for anti-CMV, IgM, and anti-CMV IgG antibodies and presence of CMV DNA by PCR		Ganciclovir	Recovery
Chen et al[55], 2010	5	M	Fever, cough, dyspnea, hypoxemia, ARDS	Immunocompetent; the patient developed ventilator-associated pneumonia, and died of burkhoderia sepsis	Chest XR – multiple parenchymal consolidations; chest XR disclosed “white lung” during the second week	Positive PCR; bronchoalveolar and seroconversion of CMV IgM and IgG		NR	Died
Tambe et al[56], 2019	32	F	Fever, dyspnea, generalized rash, weakness	Immunocompromised; stage IV, classical Hodgkin’s lymphoma, treated with chemotherapy	Chest CT revealed bilateral pulmonary infiltrates and bilateral pleural effusion	CMV was detected on BAL culture; serum quantitative CMV PCR was positive		Ganciclovir and valganciclovir	Recovery
Boussouar et al[57], 2018	47	F	Dry cough, chest pain and fever	Immunocompromised; orthotopic heart transplant and immunosuppressive treatment was initiated with corticosteroids, cyclosporine, and mycophenolate	Chest XR - alveolar opacities with upper lobe predominance; chest CT revealed consolidation in the right upper lobe associated with septal thickening and multiple nodules	Blood CMV PCR, which has been undetectable	Lung biopsy showed nuclear inclusions suggestive of CMV infection; IHC showed nuclear positivity for CMV	Ganciclovir and valganciclovir	Recovery
Haddad et al[58], 1984	18	M	Fever, chills, non-productive cough, severe hypoxia requiring intubation	Immunocompromised; sickle cell thalassemia	Chest XR suggested early pulmonary edema and cardiomegaly	On postmortem culture of lung parenchyma, CMV grew in 5 d		NR	Died
Katagiri et al[59], 2008	35	F	Deterioration of lupus nephritis and received treatment with a high dose of steroid and cyclosporine	Immunocompromised; SLE with increased risk of opportunistic infection	Chest X-ray showed bilateral pleural effusion; chest CT revealed a cavitary lesion in the right middle lobe of the lung	Positive for CMV; antigenemia		Ganciclovir	Recovery
Ayyappan et al[60], 2006	72	M	Fever, productive cough, worsening breathlessness and tenderness in epigastrium	Immunocompromised; rheumatoid arthritis-related interstitial lung disease, on corticosteroids and cyclophosphamide	Chest XR showed bilateral consolidation; chest CT revealed cavitating masses in the right upper lobe & lingula and diffuse interstitial fibrosis	PCR assay of BAL fluid was positive for CMV	Gastric biopsy - intracytoplasmic viral inclusions consistent with CMV gastritis; transbronchial lung biopsy showed intracytoplasmic viral inclusion	Gancyclovir	Recovery
Manian et al[61], 1993	32	F	Fever, non-productive cough, worsening oxygenation	Immunocompetent	Chest X ray - bilateral interstitial infiltrates	Enzyme immune-assay showed that CMV IgG and CMV IgM were positive		Ganciclovir	Recovery
McCormack et al[62], 1998	31	M	Fever, abdominal pain, jaundice, cough, palpitations, shortness of breath with atrial fibrillation	Immunocompetent	Chest radiograph showed bilateral interstitial pulmonary infiltrates	EIA for antibodies to CMV showed a strong reaction to IgM and a weak reaction to IgG	A urine culture yielded CMV; a cytopathic effect was observed and con-firmed by immunofluorescence	Ganciclovir	Recovery
Najjar et al[63], 2004, Case 1	34	F	Fever	Immunocompromised; SLE with renal failure on haemodialysis	Chest XR - bilateral infiltrates; chest CT - bilateral peripheral parenchymal infiltrates and a cavitating mass in right lower lobe	A CMV antigenaemia assay was positive and CMV isolation in blood	Histological findings included numerous intranuclear and intracytoplasmic CMV inclusions confirmed by IHC	IV ganciclovir and IV IgG	Recovery
Najjar et al[63], 2004, Case 2	33	M	Fever, dyspnoea, worsening renal function	Immunocompromised; SLE, class IV lupus, nephritis treated with chronic steroid therapy, azathioprine, and cyclophosphamide	Chest CT revealed a right upper lobe thick-walled cavitary lesion	Serology revealed raised CMV IgM & IgG	HPE - evidence of focal interstitial fibrosis, accumulation of intraalveolar macrophages, and CMV with intracytoplasmic and nuclear inclusions in the lining alveolar cells	Gancyclovir	Recovery
Kanika et al	32	M	Fever, dyspneia, hypotension, jaundice	Immunocompetent	MRI showed hepatitis and pancreatitis; CT showed GGO	Serum PCR with a high viral load	Liver biopsy suggestive of drug induced liver injury and immunochemistry negative for CMV	Ganciclovir	Recorvery

B/L: Bilateral; GGOs: Ground glass opacities; CT: Computed tomography; ARDS: Acute respiratory distress syndrome; SLE: Systemic lupus erythematosus; IgG: Immunoglobulin G; IgM: Immunoglobulin M; HRCT: High resolution CT; IHC: Immunohistochemistry; BAL: Bronchoalveolar lavage; HPE: Histopathological examination; EIA: Enzyme immune assay; PCR: Polymerase chain reaction.

Table 2 Baseline features of 45 patients with cytomegalovirus pneumonia

Variable	Patients, n = 45 (100%)
Age group
0–15 yr	7 (15.6)
16–45 yr	25 (55.6)
46–75 yr	13 (28.8)
Sex
Male	26 (58)
Female	19 (42)
Symptoms
Fever	37 (82)
Cough	24 (53)
Dyspnoea	34 (76)
Resp. distress	26 (58)
Immune status
Immunocompetent	16 (36)
Immunocompromised	29 (64)
Radiograhic findings
Chest X-ray	32 (71)
Thoracic CT	31 (69)
Serology
Blood/serum	40 (89)
Bronchoalveolar fluid (BAL)	18 (45)
Specific tests
Immunohistochemistry	11 (24)
Biopsy - histopathology	12 (27)
Treatment	38 (84)
Recovery	40 (89)
Died	4 (9)

Table 3 Summary of data collected

	Immunocompetent	Immunocompromised
Total	16	29
Fever	13	24
Cough	11	13
Dyspnoea	12	22
Respiratory distress	10	16
Treatment	12	26
Recovered	15 (94%)	25 (86%)