Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality.

PURPOSE: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. RESULTS: CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010-1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993-0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223-5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852-8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757-1721, p = 0.528). CONCLUSION: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

Impact of the COVID-19 Pandemic on the Diagnosis of Congenital Cytomegalovirus Infection in Spain.

We conducted an observational study performed within the Spanish Registry of Children with congenital cytomegalovirus (cCMV) to evaluate the impact of the COVID-19 pandemic on the diagnosis of new cases of cCMV. Our study suggest a significant decrease in the monthly rate of new cCMV diagnoses during the COVID-19 pandemic.

CMV seropositivity is a potential novel risk factor for severe COVID-19 in non-geriatric patients.

BACKGROUND: COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19. Herpes simplex virus (HSV) serostatus was investigated as control. METHODS: National German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models. RESULTS: Non-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities. CONCLUSIONS: We identified 'CMV-seropositivity' as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Cytomegalovirus coinfection in patients with severe acute respiratory syndrome coronavirus 2 infection: a systematic review of reported cases.

BACKGROUND: Dysfunction of both the innate and the adaptive immune systems is observed in severe coronavirus disease 2019 which, together with administration of immunosuppressive drugs, could lead to cytomegalovirus coinfection or reactivation associated with a poorer outcome. The current study aimed to systematically review the pattern, presentations, clinical course and outcome of patients with severe acute respiratory syndrome coronavirus 2 and cytomegalovirus coinfection. METHODS: Three online databases, PubMed, Scopus and Web of Science, were searched, and after excluding duplicates and irrelevant reports, eligible articles were identified. Information about patients' age and gender, comorbidities, presentations of coronavirus disease 2019 and cytomegalovirus, treatment courses and outcomes were extracted. RESULTS: A total of 34 reports with 59 patients with coinfection were considered to be eligible for data extraction. A majority of patients were middle-aged or elderly (84.5%). More than three-fourths (79.2%) had at least one comorbidity. Cytomegalovirus viremia was documented in 43 patients. The most common end organ involved was the gastrointestinal tract in 13 patients (48.1% of 27 patients with end organ involvement), mostly as cytomegalovirus colitis, followed by the respiratory tract in 12 patients. There was a significant association between intubation and fatal outcome (p = .011). CONCLUSION: We comprehensively reviewed published cases with coronavirus disease 2019 and cytomegalovirus reactivation. The findings may assist in appraising signs and symptoms for early suspicion, detection and treatment in patients with unusual clinical courses or with severe, prolonged or unexplained deterioration of end organ function.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

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

Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID-19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID-19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID-19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV-deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti-CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection-related mortality. The cumulative incidences of CMV infection and anti-CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%-39.0%) and 12.3% (95% CI, 4.8%-23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13-16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV-DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID-19 should be limited.

Lower prevalence of congenital cytomegalovirus infection in Portugal: possible impact of COVID-19 lockdown?

Cytomegalovirus (CMV) is the most frequent cause of congenital infection all over the world. Its prevalence ranges from 0.2 to 2.2%. Transmission from children to their pregnant mothers is a well-known risk factor, particularly if they attend a childcare centre. This study aims to compare the prevalence of CMV congenital infection (CMV_CI) in Portugal (Lisbon) between two studies, performed respectively in 2019 and 2020. In the 2019 study, performed in two hospitals, we found a 0.67% CMV_CI prevalence, using a pool strategy previously tested with saliva samples. In the 2020 study, using the same pool approach in four hospitals (the previous and two additional), and based on 1277 samples, the prevalence was 0.078%.Conclusion: The close temporal coincidence with COVID-19 lockdown suggests that these measures may have had a significant impact on this reduction, although other explanations cannot be ruled-out. What is Known: • Cytomegalovirus is the leading cause of congenital infection. • Behavioural measures decrease cytomegalovirus seroconversion in pregnant women. What is New: • From 2019 to 2020 there was a significant reduction in the prevalence of congenital CMV infection.

Viral Infections in Burns.

Background: Viral infections after burns are less common than bacterial infections but usually occur in the more severely burned patients and have been associated with poor outcomes. Methods: Retrospective reviews and case series were examined to provide an overview of the management of viral infections in the burn patient. Results: The most common viral pathogens in these patients are the herpesviruses, which include herpes simplex, varicella zoster, cytomegalovirus, and human herpesvirus 6. Established viral infections that may complicate patient management include human immunodeficiency virus, hepatitis B and C, and, more recently, the novel coronavirus SARS-CoV-2. Herpesvirus infections can occur as primary or nosocomial pathogens but clinical manifestations most commonly are re-activation of latent viral infection. Because of the paucity of data in the burn population, much of the evidence for specific treatments is extrapolated from patients with severe immunosuppression or critical illness. Antiviral therapy is employed for the burn patient with herpesvirus infections. This is an area of active study, and further research is needed to better understand the risks, clinical manifestations, and attributable morbidity and mortality of viral infections. Conclusions: Major burn injury results in immunosuppression and viral infection in a small number of patients. Recognition and antiviral therapy are employed, but additional studies are necessary to improve outcomes in these patients.

Infection as a Stroke Risk Factor and Determinant of Outcome After Stroke.

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.

Iranian kidney transplant recipients with COVID-19 infection: Clinical outcomes and cytomegalovirus coinfection.

BACKGROUND: There is a high risk of COVID-19 in kidney transplant recipients (KTRs) because of chronic immunosuppression and severe cytomegalovirus (CMV) pneumonitis. CASE PRESENTATION: A case series of 10 KTRs with COVID-19 in Iran was developed. Participants consisted of two female and eight male patients, aged 46-68 years old. The data related to clinical laboratory tests, outcomes, diagnosis, and drug treatments were collected. The RT-PCR confirmed the COVID-19 infection in KTRs. The assessment of serum biochemical and blood hematological factors showed that there was a strong correlation between COVID-19 intensity and high serum Cr, BUN, and ALT levels, high CRP concentration, and lower lymphocyte and platelet counts in male KTRs. Ground-glass opacity (GGO) was the main radiologic pattern visible on both chest radiographs of computed tomography scans. The COVID-19 and CMV coinfection in KTRs resulted in large-size kidneys with severe parenchymal echogenicity and hydronephrosis. The combined use of effective antibiotic and antiviral drugs was suitable to prevent COVID-19 progression in KTRs. CONCLUSIONS: The coincidence of COVID-19 and CMV in KTRs may potentially increase the mortality risk of patients. The levels of Cr, BUN, ALT, and CRP as well as lymphocytes count in these patients should be continuously controlled.

Why the elderly appear to be more severely affected by COVID-19: The potential role of immunosenescence and CMV.

The significantly higher mortality rates seen in the elderly compared with young children during the coronavirus disease 2019 (Covid-19) pandemic is likely to be driven in part by an impaired immune response in older individuals. Cytomegalovirus (CMV) seroprevalence approaches 80% in the elderly. CMV has been shown to accelerate immune ageing by affecting peripheral blood T cell phenotypes and increasing inflammatory mediated cytokines such as IL-6. The elderly with pre-existing but clinically silent CMV infection may therefore be particularly susceptible to severe Covid-19 disease and succumb to a cytokine storm which may have been promoted by CMV. Here, we evaluate the potential role of CMV in those with severe Covid-19 disease and consider how this relationship can be investigated in current research studies.