Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID‐19

Yamamoto, Yuji; Shiroyama, Takayuki; Hirata, Haruhiko; Kuge, Tomoki; Matsumoto, Kinnosuke; Yoneda, Midori; Yamamoto, Makoto; Uchiyama, Akinori; Takeda, Yoshito; Kumanogoh, Atsushi

doi:10.1002/jmv.27421

Cited by 18 publications

(23 citation statements)

References 39 publications

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“…CMV infection was associated with lymphopenia on ICU admission, prolonged mechanical ventilation, and increased mortality. Similar results have been reported in other clinical series (Yamamoto et al, 2021). CMV infection was not reported in any of the 24 autopsy series we reviewed.…”

Section: Discussionsupporting

confidence: 91%

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies

et al. 2022

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The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9–108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.

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Section: Discussionsupporting

confidence: 91%

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies

et al. 2022

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“…Prolonged corticosteroid therapy is also an important risk factor for COVID-19. 19,20 In the present study, steroid use was also a risk factor for CMV reactivation, contrary to a previous study.…”

Section: Discussioncontrasting

confidence: 99%

Active Surveillance of Cytomegalovirus Infection, Pneumocystis Pneumonia, and Pulmonary Aspergillosis in Critically Ill Patients with COVID-19

Kim,

Lee,

Lee

et al. 2024

Preprint

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Diagnosing opportunistic infections is important in critically ill patients with coronavirus disease 2019 (COVID-19); however, incidence and risk determination are challenging because biopsy is difficult. Therefore, this study comprehensively analyzed the risk factors using active surveillance data. Active surveillance included weekly serum cytomegalovirus, sputum Pneumocystis jirovecii, and galactomannan test testing. The incidence and risk of Pneumocystis pneumonia (PCP) and COVID-19-associated pulmonary aspergillosis (CAPA) were determined from clinical features. Among 210 patients who underwent active surveillance, serum cytomegalovirus, sputum pneumocystis, and galactomannan antigens were detected at least once in 29.0%, 7.6%, and 59.0% of patients, respectively, with first detection at medians of weeks 3 (interquartile range [IQR] 1–4), 0 (0–0.25), and 0 (0–1), respectively. PCP and CAPA occurred in 1.4% and 14.3% of patients, respectively, with diagnoses at medians of weeks 0 (0–0.5), and 2 (1–3) weeks. Treatment for CMV was started at a median of 4 (3–5) weeks. High-dose steroids were risk factors for cytomegalovirus viremia and CAPA. Cytomegalovirus viremia tended to develop and be diagnosed later than CAPA. Compared to CAPA, the incidence of Pneumocystis jiroveci pneumonia (PJP) was low in critically ill patients with COVID-19.

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“…The detailed screening process is available in Figure 1. Finally, 32 articles were included in our systematic review 15,18–48 . The characteristics of included studies are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Reactivation of herpesviruses during COVID‐19: A systematic review and meta‐analysis

Shafiee

Athar

Amini

et al. 2023

Reviews in Medical Virology

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To provide a comprehensive systematic review and meta‐analysis regarding the cumulative incidence (incidence proportion) of human herpesvirus (HHV) reactivation among patients with coronavirus disease 2019 (COVID‐19), we searched PubMed/MEDLINE, Web of Science, and EMBASE up to 25 September 2022, with no language restrictions. All interventional and observational studies enrolling patients with confirmed COVID‐19 and providing data regarding HHV reactivation were included. The random‐effects model was used in the meta‐analyses. We included information from 32 studies. HHV reactivation was considered a positive polymerase chain reaction result taken at the time of COVID‐19 infection. Most of the included patients were severe COVID‐19 cases. The pooled cumulative incidence estimate was 38% (95% Confidence Intervals [CI], 28%–50%, I2 = 86%) for herpes simplex virus (HSV), 19% (95% CI, 13%–28%, I2 = 87%) for cytomegalovirus (CMV), 45% (95% CI, 28%–63%, I2 = 96%) for Epstein‐Barr virus (EBV), 18% (95% CI, 8%–35%) for human herpesvirus 6 (HHV‐6), 44% (95% CI, 32%–56%) for human herpesvirus 7 (HHV‐7), and 19% (95% CI, 14%–26%) for human herpesvirus 8 (HHV‐8). There was no evidence of funnel plot asymmetry based on visual inspection and Egger's regression test for the results of HSV (p = 0.84), CMV (p = 0.82), and EBV (p = 0.27) reactivation. In conclusion, the identification of HHV reactivation in severe COVID‐19 patients is helpful in the management of patients as well as the prevention of complications. Further research is required to elucidate the interaction between HHVs and COVID‐19. Systematic review registration: PROSPERO CRD42022321973.

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Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID‐19

Cited by 18 publications

References 39 publications

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies

Active Surveillance of Cytomegalovirus Infection, Pneumocystis Pneumonia, and Pulmonary Aspergillosis in Critically Ill Patients with COVID-19

Reactivation of herpesviruses during COVID‐19: A systematic review and meta‐analysis

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