Abstract
To investigate the characteristics and risk factors of cytomegalovirus (CMV) infection in patients with dermatomyositis (DM) and explore whether CMV infection plays a role in the prognosis of patients with DM. The retrospective reviewed patients with DM admitted to the hospital from October 2017 to June 2022 and the enrolled patients who were assessed for CMV infection. The clinical characteristics and prognosis of the patients with CMV infection were compared to those without CMV. Of the 181 patients with DM, 53 (29.2%) suffered from CMV infection. The prevalence of CMV infection in the anti-MDA5( +) DM group was higher than it was in the anti-MDA5(-) DM group (38.7% vs. 16.0%, P = 0.001). Multivariate analyses demonstrated that the ILD (OR 5.11, 95% CI 1.74–15.26, P = 0.003), other infections (OR 6.24, 95% CI 1.63–23.89, P = 0.007), the cumulative dose of glucocorticoids (OR 5.19, 95% CI 2.44–11.02, P < 0.001), usage of CTX (OR 8.49, 95% CI 2.28–31.54, P = 0.001), ALB ≦ 30 g/L (OR 3.19, 95% CI 1.03–9.85, P = 0.043) were independent risk factors for CMV infection in patients with DM. Patients in the CMV-infection group showed significantly higher incidences of other infections than those in the CMV-infection-negative group. Higher mortality was observed in the CMV infection group than in the without CMV infection group. CMV infection occurred in patients with DM frequently and was found to be relevant to death. The cumulative dose of glucocorticoids, ILD, useage of CTX, hypoproteinemia, and other infections were contributing factors in the development of CMV infection in patieents with DM.
Keywords: Dermatomyositis, Cytomegalovirus infection, Characteristics, Risk factors, Prognosis
Introduction
Cytomegalovirus (CMV) is a member of the herpes virus family found ubiquitously, infecting most humans [1, 2]. Primary CMV infection is usually asymptomatic or presents mild syndrome in immunocompetent healthy hosts. However, when CMV infection occurs in immunocompromised patients, the host immune system cannot control virus replication, leading to invasive CMV diseases, causing serve morbidity and mortality [3].
Because of immune system dysfunction and intensive immunosuppressive treatment, the risk of CMV infection may increase among patients with rheumatic diseases. It was reported that the incidence of CMV infection in patients with rheumatic diseases was 31–50%, which varies depending on the patient's setting, type of disease, treatment regimen, and detection methods for CMV [3–9]. In addition, CMV may be an environmental factor that triggers autoimmune reactions and plays a vital role in the pathogenesis of rheumatic diseases. Documented mechanisms by which CMV-induced autoimmunity include molecular mimicry and bystander activation [10]. The relationship between rheumatic disease and CMV infection needs more attention and exploration. However, little study is available on CMV infection in patients with DM. Therefore, this study aims to investigate the characteristics and risk factors of cytomegalovirus infection in patients with DM and explore whether CMV infection plays a role in the prognosis of patients with DM.
Material and Methods
Patients
With the approval of the bioethics committee of the hospital (NO.1021), this study retrospectively analyzed 181 Chinese patients with DM who were admitted to the hospital between October 2017 and June 2022. All patients met either the classification of DM proposed by Bohan and Peter or the 2018 European Neuro Muscular Centre International Workshop guidelines [11, 12]. Patients were excluded if they were younger than 18 years, had concomitant overlapping rheumatic diseases, conceived, or had human immunodeficiency virus infection. All patients completed CMV-DNA testing within 1 week of admission. The clinical data, including demographics, clinical manifestations, complications, laboratory findings, and treatment regimens within 30 days before admission, were retrospectively collected from all patients by reviewing their medical records. The outcomes for all patients were obtained through medical records or telephone follow-ups until February 2023.
Interstitial lung disease (ILD) was diagnosed based on clinical manifestations, physical examinations, and high-resolution CT scans. Some patients developed progressive dyspnea and progressive hypoxemia within 1 month after the onset of respiratory symptoms, and their chest radiography revealed new interstitial abnormalities [13]. This type of ILD is defined as rapidly progressive interstitial lung disease [14].
New-onset DM (NDM) patients were defined as those who first diagnosed with DM at the hospital and never received glucocorticoids and immunosuppressant therapy. Post-therapy DM (PDM) patients were defined as those who were diagnosed with DM and received treatment with glucocorticoids or immunosuppressants.
CMV Infection and CMV Diseases
CMV infection was defined as a blood CMV-DNA concentration greater than 400 copies/ml or positive nucleic acid detection in any body fluid or tissue specimen, including bronchoalveolar lavage (BAL), plasma, and others, as previous studies reported [15]. CMV-DNA was detected via a PCR fluorescence probe method using the Diagnostic Kit for Quantification of Human Cytomegalovirus DNA in the hospital (Sansure Biotech Inc, China). CMV pneumonia was defined by the presence of signs and/or symptoms of pulmonary disease combined with the detection of CMV in bronchoalveolar lavage fluid or lung tissue samples [15].
Statistical Analysis
Analyzes were performed with SPSS software (version 23) and GraphPad Prism software (version 8.01). Values that were normally distributed are expressed as mean ± standard deviation (SD), while data that were not normally distributed are presented as the median and interquartile range (IQR). Differences in quantitative data were compared using Mann–Whitney U-test or Student's t-test. Categorical variables were reported as frequencies or percentages and compared using the chi-square test or Fisher exact test. Additionally, multivariate analysis was performed with logistic regression to identify the independent risk factors for CMV infection in patients with DM. Results from multivariable analysis were described as an odds ratio (OR) with a 95% confidence interval (CI). Kaplan–Meier curved the survival probability. The two-tailed P-value was interpreted as significant when it was less than 0.05 for all comparisons.
Results
Incidence and Clinical Features of CMV Infection in Patients with DM
A total of 181 patients were enrolled in this study, and CMV infection was observed in 53 patients (29.2%). Among the 53 patients, the median age was 52 ± 9 years, and the ratio of female: male was 37:16. 8 NDM patients were found, and 45 PDM patients were observed. Among the PDM patients, the median duration from diagnosis of DM to the detection of CMV infection was 8 weeks, and the median cumulation of glucocorticoids was 1460 mg.
NDM Patients with CMV Infection and Without Infection
There were 77 new-onset DM (NDM) patients in the current study, and CMV infection was observed in 8(10.3%) patients. A comparison of clinical characteristics and immunological parameters between the NDM patients with the CMV infection group and without the CMV infection group was summarized in Table 1. NDM patients with CMV infection exhibited a high prevalence of dyspnea and a higher level of C reaction protein (CRP). The CMV infection group had a lower level of IgG compared to the without CMV infection group. This findings indicate CMV infection may exacerbate the illness of DM.
Table 1.
Comparison of clinical features of NDM patients with or without CMV infection
| Clinical features* | Newly onset DM | P value | |
|---|---|---|---|
| CMV infection(n = 8) | Without CMV infection(n = 69) | ||
| Age (years) | 57 (48–60) | 50 (41–58) | 0.151 |
| Gottron signs/Helitrop rash | 2 (25.0%) | 29 (42.0%) | 0.583 |
| Skin ulcers | 1 (12.5%) | 6 (8.7%) | 1.000 |
| Arthritis/Arthralgia | 1 (12.5%) | 33 (47.8%) | 0.126 |
| Myalgia | 1 (12.5%) | 22 (31.9%) | 0.468 |
| Muscle weakness | 0 (0) | 15 (21.7%) | 0.318 |
| Dyspnea | 6 (75.0%) | 21 (30.4%) | 0.035 |
| ILD | 6 (75.0%) | 37 (53.6%) | 0.437 |
| RP-ILD | 2 (25.0%) | 9 (13.0%) | 0.703 |
| Bacterial infection | 8 (100.0%) | 42 (60.9%) | 0.071 |
| Fungal infection | 2 (25.0%) | 12 (17.4%) | 0.965 |
| WBC (10^9/L) | 9.08 (5.16–16.00) | 6.47 (3.95–8.07) | 0.042 |
| Hb (g/L) | 116 ± 13 | 112 ± 16 | 0.377 |
| PLT (10^9/L) | 250 (216–273) | 228 (151–279) | 0.346 |
| Lymphocytes (10^9/L) | 0.70 (0.47–1.17) | 0.87 (0.62–1.27) | 0.289 |
| CD3 + T cells (/ul) | 498 (319–719) | 579 (381–798) | 0.404 |
| CD4 + T cells (/ul) | 277 (204–313) | 327 (224–552) | 0.263 |
| CD8 + T cells (/ul) | 181 (141–240) | 170 (113–284) | 0.796 |
| IgG (g/L) | 9.17 (7.51–9.72) | 14.1 (11.6–17.3) | < 0.001 |
| IgA (g/L) | 1.78 (1.40–3.27) | 2.48 (1.89–3.11) | 0.113 |
| IgM (g/L) | 1.40 (0.95–1.94) | 1.50 (1.06–1.99) | 0.553 |
| LDH (IU/L) | 381 (288–448) | 335 (294–438) | 0.764 |
| CK (IU/L) | 32 (23–62) | 111 (53–644) | 0.003 |
| CRP (mg/L) | 30.7 (15.7–42.9) | 7.6 (3.5–37.9) | 0.036 |
| ESR (mm/h) | 50.9 (49.4–56.0) | 50.9 (34.5–63.0) | 0.731 |
| ANA ≥ 1:320 | 0 (0) | 14 (20.3%) | 0.355 |
P-value less than 0.05 is significant
*Continuous variables are expressed as median and interquartile range. Categorical variables are n (%)
ILD, interstitial lung disease; RP-ILD, rapid progressive interstitial lung disease; IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M; LDH, Lactate dehydrogenase; CK, Creatine kinase; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; ANA, Antinuclear antibody
Association Between CMV Infection and Myositis Special Antibodies (MSAs) in Patients with DM
The anti-melanoma differentiation associated gene 5 (MDA5) antibodies were the most common MASs in the CMV infection group, which were detected in 44 (77.4%) patients. The prevalence of MDA5 antibodies in the CMV infection group was higher than those without the CMV infection group (77.4% vs. 50.8%, P = 0.001). 4 patients were found MSAs all negative. Anti-syntheses antibodies (ARS) were identified in 3 (5.7%) patients, and 3 (5.7%) patients carried anti-nuclear matrix protein 2 (NXP-2) antibodies, followed by anti-transcription intermediary factor 1γ (TIF1γ) antibodies and the anti-Mi-2 antibodies were detected in 1 (1.9%) patient respectively. A Comparison of clinical features between anti-MDA5( +) DM and anti-MDA5(-) DM showed that anti-MDA5( +) DM patients were more likely to suffer from CMV infection (38.7% vs. 16.0%, P = 0.001).
CMV Disease and Antiviral Therapy in the CMV Infection Group
Among 53 patients with CMV infection, 11 developed CMV pneumonia, all of which developed respiratory failure. Pancytopenia was observed in 10 patients. The median CMV-DNA load was 1920 copies/ml (415 ~ 39,700). 48 patients received antivirus treatment; ganciclovir was the most common drug. The median time for antiviral was 8 days. After treatment, the virus load of 8 cases turned negative, and 16 cases decreased (25 cases reexamined). The impact of antiviral therapy on prognosis cannot be able to explore due to the small sample size. A prolonged time of antiviral treatment in DM patients with CMV infection is needed.
Association Between CMV Infection and Other Infections
Other infections occurred in DM patients with CMV infection frequently. Of the microbiologically documented infections, the most common microorganisms infecting patients were bacteria (86.8%). Among the bacteria, Acinetobacter baumannii was the most common, followed by Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Additionally, a significant proportion (26.4%) of patients developed a fungal infection; 9 cases were infected with Candida, five were infected with Pneumocystis jirovecii pneumonia (PJP), and 2 were identified with Aspergillus. There were 12(22.6%) patients with other viral infections, 7 cases of EB virus, 3 cases of Herpes simplex virus (HSV), and 2 cases of Rhinovirus. There was a substantial difference in the incidence of bacterial (86.8% vs. 56.4%, P < 0.001) and fungal (26.4% vs. 13.3%, P = 0.033) infections despite comparable other viral infections (41.5% vs. 25.8%, P = 0.118) rates between CMV infection group and CMV infection negative group.
Risk Factors for CMV Infection in Patients with DM
All patients were divided into the CMV infection group and the without CMV infection group, as shown in Table 2. Based on demographic data, no significant differences were observed in the proportion of females, the median age, BMI, and the duration. In terms of clinical manifestations, the patients in the CMV infection group were more likely to present with skin ulcers and dyspnea. Other clinical features, such as Gottron signs or Helitrop rash, mechanic hands, dysphagia, and arthritis or arthralgia, were not significant differences. Regarding complications, patients in the CMV infection group were more likely to suffer from ILD and other infections. In the comparison of laboratory data, patients with CMV infection had lower baseline lymphocyte counts, CD3 + T cells, CD4 + T cells, IgG, IgA, and IgM, with higher baseline serum CRP and lactate dehydrogenase (LDH). The prevalence of lower albumin (≦ 30 g/L) was higher in the CMV infection group compared to the CMV infection-negative group. Comparisons of different myositis-special antibodies between the CMV infection and the without CMV infection group showed that the MDA5 antibodies were more common. No significant differences were found between the two groups with regards to the following antibodies: anti-transcription intermediary factor 1 γ antibodies, anti-nuclear matrix protein 2 antibodies, anti-Mi2 antibodies, and myositis special antibodies all negative. The treatment regimens were also significantly different: the cumulative dose of glucocorticoids and the rate of cyclophosphamide (CTX), calcineurin inhibitor (CNI), and tofacitinib (TOF). Multivariate logistic regression analysis revealed that cumulative dose of glucocorticoids (OR 5.19, 95% CI 2.44–11.02, P < 0.001), ILD(OR 5.11, 95% CI 1.74–15.26, P = 0.003), usage of CTX(OR 8.49, 95% CI 2.28–31.54, P = 0.001), ALB ≦ 30 g/L(OR 3.19, 95% CI 1.03–9.85 P = 0.043), with other infections(OR 6.24, 95% CI 1.63–23.89, P = 0.007) were independent risk factors for CMV infection, while serum level of IgG was an independent protective factor (OR 0.85, 95% CI 0.76–0.95, P = 0.004).
Table 2.
Comparison of clinical characteristics of DM patients with or without CMV infection
| Clinical features* | CMV infection (n = 53) | Without CMV infection (n = 128) | P value |
|---|---|---|---|
| Female | 37 (69.8%) | 92 (71.9%) | 0.780 |
| Onset age (years) | 52 ± 9 | 49 ± 13 | 0.137 |
| BMI (kg/m2) | 22.0 ± 2.5 | 22.6 ± 2.8 | 0.216 |
| Duration (months) | 4 (2–6) | 4 (1–8) | 0.406 |
| Gottron signs/Helitrop rash | 31 (58.5%) | 58 (45.3%) | 0.107 |
| Mechanic hands | 7 (13.2%) | 14 (10.9%) | 0.664 |
| Skin ulcer | 10 (18.9%) | 11 (8.6%) | 0.050 |
| Dysphagia | 7 (13.2%) | 15 (11.7%) | 0.780 |
| Arthritis/Arthralgia | 21 (39.6%) | 59 (46.1%) | 0.425 |
| Myalgia | 19 (35.8%) | 43 (33.6%) | 0.771 |
| Muscle weakness | 15 (28.3%) | 44 (34.3%) | 0.566 |
| Fever | 21 (39.6%) | 33 (25.8%) | 0.064 |
| Cough | 29 (54.7%) | 50 (39.1%) | 0.053 |
| Dyspnea | 32 (60.4%) | 46 (35.9%) | 0.003 |
| ILD | 39 (73.6%) | 71 (55.5%) | 0.023 |
| RP-ILD | 10 (18.9%) | 14 (10.9%) | 0.152 |
| Tumor | 0 (0) | 5 (3.9%) | 0.337 |
| Diabetes | 9 (17.0%) | 17 (13.3%) | 0.518 |
| Hypertension | 6(11.3%) | 11 (8.6%) | 0.567 |
| Other infections | 47 (88.7%) | 80 (62.5%) | < 0.001 |
| WBC (109/L) | 7.46 (5.34–10.13) | 6.47 (4.75–8.87) | 0.082 |
| Hb (g/L) | 115 ± 17 | 122 ± 17 | 0.031 |
| PLT (109/L) | 211 (150–254) | 202 (145–274) | 0.836 |
| Lymphocytes (109/L), | 0.70 (0.45–1.21) | 0.91 (0.61–1.29) | 0.041 |
| CD3+T cells (/ul) | 472 (216–641) | 585 (381–838) | 0.020 |
| CD4+T cells (/ul) | 180 (107–331) | 341 (222–555) | < 0.001 |
| CD8+T cells (/ul) | 202 (82–331) | 170 (116–291) | 0.582 |
| ALB (g/L) | 0.002 | ||
| ≤ 30 | 18 (34.0%) | 18 (14.1%) | |
| > 30 | 35 (66.0%) | 110 (85.9%) | |
| IgG (g/L) | 9.79 (7.79–12.80) | 13.45 (10.52–16.30) | < 0.001 |
| IgA (g/L) | 1.75 (1.33–2.51) | 2.30 (1.68–3.28) | 0.002 |
| IgM (g/L) | 1.14 (0.78–1.66) | 1.41 (0.98–1.97) | 0.015 |
| CRP (mg/L) | 22.30 (9.07–62.2) | 7.90 (3.71–27.37) | < 0.001 |
| ESR (mm/h) | 51.2 (45.0–54.5) | 50.9 (31.0–65.0) | 0.547 |
| CK (IU/L) | 31 (20–76) | 109 (46–529) | < 0.001 |
| LDH (IU/L) | 417 (293–495) | 330 (250–435) | 0.024 |
| AST (IU/L) | 42 (22–60) | 56 (27–105) | 0.010 |
| ALT (IU/L) | 37 (26–57) | 46 (23–79) | 0.240 |
| MDA-5 | 41 (77.4%) | 65 (50.8%) | < 0.001 |
| ARS | 6 (11.3%) | 28 (21.9%) | 0.098 |
| NXP2 | 3 (5.7%) | 11 (8.6%) | 0.714 |
| TIF1-γ | 1 (1.9%) | 11 (8.6%) | 0.186 |
| Mi-2 | 1 (1.9%) | 4 (3.1%) | 1.000 |
| MSA (-) | 4 (7.5%) | 7 (5.5%) | 0.849 |
| Glucocorticoid dose (g)a | 1.30 (0.58–1.52) | 0 (0–0.57) | < 0.001 |
| Methylprednisolone pulse | 1 (1.9%) | 5 (3.9%) | 0.815 |
| CTX | 20 (37.7%) | 5 (3.9%) | < 0.001 |
| CNI | 13 (24.5%) | 6 (4.7%) | < 0.001 |
| MMF | 1 (1.9%) | 6 (4.7%) | 0.641 |
| MTX | 1 (1.9%) | 6 (4.7%) | 0.641 |
| AZA | 1 (1.9%) | 3 (2.3%) | 1.000 |
| HCQ | 10 (18.9%) | 18 (14.1%) | 0.266 |
| Thalidomide | 5 (9.4%) | 3 (2.3%) | 0.086 |
| RTX | 2 (3.8%) | 0 (0) | 0.153 |
| TOF | 6 (11.3%) | 0 (0) | 0.001 |
P-value less than 0.05 is significant
*Continuous variables are expressed as median and interquartile range. Categorical variables are n (%)
BMI, body mass index; ILD, interstitial lung disease; RP-ILD, rapid progressive interstitial lung disease; IgG, immunoglobulin G; IgA, immunoglobulin A; IgM, immunoglobulin M; LDH, Lactate dehydrogenase; CK, Creatine kinase; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; MDA5, melanoma differentiation associated gene 5; ARS, aminoacyl tRNA synthetase; TIF1γ, transcription intermediary factor 1 γ; NXP2, nuclear matrix protein 2; MSA, myositis special antibody; a, 30 days before admission; CTX, Cyclophosphamide; CNI, Calcineurin inhibitor; MMF, Mycophenolate mofetil; HCQ, Hydroxychloroquine; AZA, Azathioprine; MTX, Methotrexate; RTX, Rituximab; TOF, Tofacitinib
Probability of Survival in DM Patients with and Without CMV Infection
Kaplan–Meier survival curves indicated the cumulative survival probability of DM patients with or without CMV infection. Survival analysis demonstrated that the CMV infection group's survival rate was lower than that of the without CMV infection group (Fig. 1). The survival of the DM cohort without CMV infection was 89.3% at 1 month, 88.4% at 3 months, and 87.5% at 6 months. However, after CMV infection, survival declined sharply to 64.2% at 1 month, 60.3% at 3 months, and 54.7% at 6 months. Through multivariate COX analysis, CMV infection was relevant to death (HR 2.31, 95% CI 1.15–4.62, P = 0.018). In addition, age (HR 1.03, 95% CI 1.00–1.05, P = 0.015),hypoproteinemia(HR = 3.82, 95% CI 2.01–7.24, P < 0.001), RP-ILD (HR 3.22, 95% CI 1.56–6.64, P = 0.001), higher serum levels of LDH (HR 1.004, 95% CI 1.003–1.005, P < 0.001), with anti-MDA5 antibody (HR 2.91, 95% CI 1.04–8.08, P = 0.040) were another five factors that independently predicted the mortality of patients with DM, while lymphocyte counts were an independent protective factor (HR 0.29, 95% CI 0.12–0.73, P = 0.009).
Fig. 1.
Survival curves for DM patients with and without CMV infection
Discussion
This study observed that CMV infection was relevant to death in patients with DM, and approximately 30% of patients with DM developed CMV infection. Sekiguchi et al. showed that 21 out of 52 patients with DM (40.4%) developed CMV reactivation, but there are few cases in the study [16]. A prospective study described the frequency of recent CMV infection in anti-MDA5( +) DM as high as 19.1% [17]. Consistent with the latter study, this study also observed that anti-MDA5( +) DM patients were more susceptible to cytomegalovirus infection, with a prevalence as high as 38.7%. The reason for the discrepancy of frequency between this study and other reports may be due to the differences in sample size, the definition and the detection of CMV infection.
Huang et al. [17] indicated that CMV infection might play an important role in the pathogenesis of MDA5( +) DM by disrupting immunity. Krasselt et al. [18] reported that the CMV IgG titers were positively associated with the disease activity indicators in systemic lupus erythematosus (SLE). Thus, they also presumed that CMV infection may promote the clinical flares of SLE. In addition, in vitro studies suggested increased IFN-γ/IL-2 levels after stimulation of SLE peripheral blood mononuclear cells with CMV antigen [19]. These observations identified a close relationship between CMV and rheumatic diseases. Similarly, The current study observed that new-onset patients with CMV infection showed server illnesses, including dyspnea, higher inflammation indicator, and lower level of serum IgG, which suggest that CMV infection may aggravate the condition of rheumatic diseases.
CMV can evolve multi mechanisms to exert immunosuppressive effects, which results in an increased rate of other infections, such as bacterial and fungal infections [20]. Ota et al. [4] found that CMV reactivation was relevant to other severe infections and infection-related deaths in patients with rheumatic diseases. Consistent with the previous study, This study observed that patients in the CMV infection group frequently suffered from other bacterial and fungal infections. Gram-negative bacteria were more common, which suggests that care should be taken to prevent bacterial and fungal infections in patients after CMV infection.
A better understanding of which patient subgroups are at risk for CMV infection could help improve their outcome. Consistent with previous studies [21–25], this study found factors such as the cumulation dose of glucocorticoid, usage of CTX, serum level of albumin and IgG, ILD, and other infections were associated with CMV infection, suggesting that both the patient's nutritional as well as immunological conditions are relevant. In subjects, CMV infection was controlled by cellular and humoral immunity [26]. Glucocorticoids and immunosuppressants such as CTX could induce CMV infection by suppressing the function of various immunocompetent cells such as B cells and T cells [27, 28]. CMV infection itself can promote susceptibility to other infections as mentioned above. On the other hand, this study revealed that other infections contribute to CMV infection. The possible explanation is that the high systemic inflammatory response to bacterial infection could trigger a CMV reaction [20]. But the association between CMV infection and inflammation is still unclear.
Whether CMV infection was associated with poor survival in DM patients was investigated in the present study. Patients with CMV infection had poorer outcomes in the current DM cohort than those without CMV infection. Previous studies reported subclinical CMV viremia is associated with increased nosocomial infections and prolonged hospitalization in patients with rheumatic disease [29]. Huang et al. [30] indicated that CMV infection was an unequivocal risk factor for the mortality of patients with SLE. The high mortality in DM patients with CMV infection warrants extensive attention.
This study had several limitations. Firstly, it was mainly a retrospective study in which a part of the patients did not test CMV-DNA. The exclusion of patients who were not evaluated for CMV-DNA would have caused selection bias and overstated the prevalence of CMV infection. Secondly, all patients were from a single center, and the number of patients with CMV infection was relatively small. Thirdly, this study did not evaluate the impact of antiviral therapy on the prognosis of patients with DM. In addition, some risk factors, such as invasive ventilation, were not further analyzed.
Conclusion
CMV infection occurred in patients with DM frequently and was found to be relevant to death. The cumulative dose of glucocorticoids, ILD, useage of CTX, hypoproteinemia, and other infections were contributing factors in the development of CMV infection in patieents with DM.
Acknowledgements
MZ: collecting and analyzing data, writing, BY: concept and proofreading, all authors contributed to the article and approved the submitted version.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declarations
Conflict of interest
The authors have no conflicts of interest to declare.
Ethical Approval
This study got permission from the Ethics Committee of West China Hospital, Sichuan University, and was based on the principles of the 1964 Declaration of Helsinki and its later amendment.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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