Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

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Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry.

INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry.

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.

Nosocomial outbreak of SARS-CoV-2 infection in a haematological unit - High mortality rate in infected patients with haematologic malignancies.

BACKGROUND: Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2. METHODS: The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2. RESULTS: Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8 %. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p < 0.05). Additionally, the probability of death was much higher in patients older than 40 years of age (p = 0.032). CONCLUSION: This study showed significantly higher mortality rate in COVID-19 patients with haematologic diseases compared to the non-infected patient group. Haematologic patients with COVID-19 have 50 % less chance of survival.

Intensive formation of coccoid forms as a feature strongly associated with highly pathogenic Helicobacter pylori strains.

The variability of Helicobacter pylori morphology and the heterogeneity of virulence factors expressed by these bacteria play a key role as a driving force for adaptation to the hostile stomach environment. The aim of the study was to determine the relationship between the presence of certain genes encoding virulence factors and H. pylori morphology. One reference and 13 clinical H. pylori strains with a known virulence profile (vacA, cagA, babA2, dupA, and iceA) were used in this study. Bacteria were cultured for 1 h and 24 h in stressogenic culture conditions, i.e., serum-free BHI broths at suboptimal conditions (room temperature and atmosphere, without shaking). H. pylori cell morphology was observed by light and scanning electron microscopy. The vacA polymorphism and the cagA and babA2 presence were positively correlated with the reduction in cell size. Exposure to short-time stressogenic conditions caused more intense transformation to coccoid forms in highly pathogenic H. pylori type I strains (35.83% and 47.5% for type I s1m2 and I s1m1, respectively) than in intermediate-pathogenic type III (8.17%) and low pathogenic type II (9.92%) strains. The inverse relationship was observed for the number of rods, which were more common in type III (46.83%) and II (48.42%) strains than in type I s1m2 (19.25%) or I s1m1 (6.58%) strains. Our results suggest that there is a close relationship between the presence of virulence genes of H. pylori strains and their adaptive morphological features.

Frequency of infection with Helicobacter pylori isolates of different antimicrobial profiles in children and adolescents: A preliminary study.

BACKGROUND: Helicobacter pylori (H. pylori) infection can occur as a mixed infection caused by several strains of H. pylori. OBJECTIVES: The aim of the study was to determine the frequency of colonization of the gastric mucosa by strains of H. pylori with different susceptibility to antimicrobial agents. MATERIAL AND METHODS: The study was carried out on gastric biopsies taken from 54 previously untreated Polish children and adolescents. Of the 15 positive cultures, from each primary medium, 6 single H. pylori colonies were isolated, making a total of 90 isolates, and the susceptibility to metronidazole (MZ), amoxicillin (AC) and clarithromycin (CH) was determined by E-test method. The presence of the cagA gene and vacA alleles (s1, s2, m1, m2) was determined by PCR. RESULTS: Positive culture for H. pylori was noted in 15/54 (27.7%) of patients. All H. pylori isolates were susceptible to AC, 27.8% were resistant to MZ and 38.9% to CH. The results showed 7/15 (46.7%) of children were infected with H. pylori strains with antibiotic heteroresistance, resistant to CH (5/15, 33.3%) and to MZ (2/15, 13.3%). The cagA + vacA s1/m2 combination was predominant genotype among detected H. pylori strains. The isolates possessing different antimicrobial susceptibility profiles in the same patient were identified. CONCLUSIONS: Microbiological analyses confirmed the presence of isolates possessing different antimicrobial susceptibility profiles in 47% of examined children with H. pylori infection. Different antimicrobial susceptibility profiles of H. pylori isolates detected in the same patient may influence the success of eradication therapy.

The Prevalence of Helicobacter pylori Infection in Symptomatic Children: A 13-Year Observational Study in the Lower Silesian Region.

BACKGROUND: Helicobacter pylori (H. pylori) infection is very common worldwide, with varying frequency. According to data from epidemiological reports, a third of the population of children in Poland are infected with H. pylori before the age of 18. In recent years, a decrease in the incidence of H. pylori infection in both children and adults has been observed in many countries. OBJECTIVES: The aim of the study was to assess the prevalence H. pylori and non-helicobacter pylori helicobacter (NHPH) infection in symptomatic children from 2000 to 2013, and to analyze the resistance of H. pylori strains to antibiotics over the 13-year study period. MATERIAL AND METHODS: The retrospective analysis was based on the results of cultures for H. pylori in 8661 untreated children undergoing their first upper gastroduodenal endoscopy because of clinical symptoms such as chronic abdominal pain/distress, epigastric pain, nausea or vomiting. Drug sensitivity to three antibiotics - amoxicillin (AM), clarithromycin (CH) and metronidazole (MZ) - was determined by the gradient diffusion method (E-test). RESULTS: Overall, among 8661 cultures analyzed, 16.05% were positive for H. pylori. The highest prevalence of infection was found in the year 2000 (23.06%) and the lowest in the year 2010 (8.90%). The prevalence of NHPH infection was low (0.2%). A three-fold increase in the number of strains resistant to both CH and MZ was noted, from 7.9% to about 22.7%. All strains were susceptible to AM. CONCLUSIONS: There has been a decline in the prevalence of H. pylori infection in symptomatic children, but this infection is still a common cause of upper gastrointestinal tract symptoms in children treated at the authors' center. Primary antibiotic resistance of H. pylori increased over the period analyzed, but primary resistance to metronidazole declined.

Mycotic Infections of the Eye.

Fungal infections of the eye are an important cause of significant visual loss and blindness in some regions of the world, especially developing countries. Ocular mycoses remain a diagnostic and therapeutic challenge to the ophthalmologist. Corneal infection is the most frequent presentation, but the orbit, eyelids, lacrimal apparatus, conjunctiva, sclera and internal structures of the eye can also be affected. Candida spp., Fusarium spp. and Aspergillus spp. are the most frequently isolated organisms in fungal keratitis and in endophthalmitis. The difficulties posed by ocular mycoses are mainly related to establishing the clinical diagnosis, isolation of the fungal pathogen and effective local treatment, particularly in infections of the cornea. The critical issue in diagnosing fungal infection of the eye is microbiological identification of the etiologic agent in clinical samples. Early diagnosis and prompt treatment allow serious complications, including blindness, to be avoided. Local, systemic and even surgical treatment is applied in the therapy.