Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study.

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital "P. Giaccone" Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox's regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student's t test for continuous variables and the Mantel-Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox's regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43-48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59-4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65-3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study).

Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.

Use of Sotrovimab in a cohort of pregnant women with a high risk of COVID 19 progression: a single-center experience.

Neutralizing monoclonal antibodies (mAbs) have been shown to reduce disease progression in patients with underlying predisposing conditions. Unfortunately, there is no evidence on the use of Sotrovimab in pregnant women. Herein we present a case series of pregnant women who received mAbs with Sotrovimab following the Italian Drug Agency (AIFA) indications. Since February 1, 2022 all pregnant women - regardless of gestational age - admitted to Obstetrics & Gynaecology of Policlinico University of Bari, with positive nasopharyngeal NAAT for SARS-CoV-2 were screened according to the AIFA indications for Sotrovimab and, if eligible, were proposed for treatment. Data on COVID-19, pregnancy, delivery, newborn outcomes, and adverse events were collected. From February 1 to May 15, 2022, 58 pregnant women were screened. Fifty (86%) patients were eligible, 19 of them (32.7%) denied their consent, in 18 cases (31%), the drug was temporarily unavailable, and the remaining 13 (22%) were treated with Sotrovimab. Out of these 13 patients, 6 (46%) were in the 3rd and 7 (54%) in the 2nd trimester of pregnancy. None of the 13 patients experienced adverse reactions due to Sotrovimab and all had a good clinical outcome. Furthermore, evaluating pre- and post-infusion clinical status and hematochemical profile, a reduction in D-dimers and an increase in SARS-CoV-2 antibodies (p < 0.01) during the 72 h following the infusion were observed. Our data, the first on the use of Sotrovimab in pregnant women, showed the safety and efficacy drug profile and its potential crucial role in preventing COVID-19 disease progression.

Anakinra in hospitalized COVID-19 patients guided by baseline soluble urokinase plasminogen receptor plasma levels: A real world, retrospective cohort study.

BACKGROUND: In patients with COVID-19 and baseline soluble urokinase plasminogen receptor plasma (suPAR) levels ≥ 6ng/mL, early administration of anakinra, a recombinant interleukin-1 receptor antagonist, may prevent disease progression and death. In case of suPAR testing unavailability, the Severe COvid Prediction Estimate (SCOPE) score may be used as an alternative in guiding treatment decisions. METHODS: We conducted a monocenter, retrospective cohort study, including patients with SARS-CoV2 infection and respiratory failure. Patients treated with anakinra (anakinra group, AG) were compared to two control groups of patients who did not receive anakinra, respectively with ≥ 6 ng/mL (CG1) and < 6 ng/mL (CG2) baseline suPAR levels. Controls were manually paired by age, sex, date of admission and vaccination status and, for patients with high baseline suPAR, propensity score weighting for receiving anakinra was applied. Primary endpoint of the study was disease progression at day 14 from admission, as defined by patient distribution on a simplified version of the 11-point World Health Organization Clinical Progression Scale (WHO-CPS). RESULTS: Between July, 2021 and January, 2022, 153 patients were included, among which 56 were treated with off-label anakinra, 49 retrospectively fulfilled prescriptive criteria for anakinra and were assigned to CG1, and 48 presented with suPAR levels < 6ng/mL and were assigned to CG2. At day 14, when comparing to CG1, patients who received anakinra had significantly reduced odds of progressing towards worse clinical outcome both in ordinal regression analysis (OR 0.25, 95% CI 0.11-0.54, p<0.001) and in propensity-adjusted multiple logistic regression analysis (OR 0.32, 95% CI 0.12-0.82, p = 0.021) thus controlling for a wide number of covariates. Sensitivities of baseline suPAR and SCOPE score in predicting progression towards severe disease or death at day 14 were similar (83% vs 100%, p = 0.59). CONCLUSION: This real-word, retrospective cohort study confirmed the safety and the efficacy of suPAR-guided, early use of anakinra in hospitalized COVID-19 patients with respiratory failure.

Incidence of bloodstream infections due to multidrug-resistant pathogens in ordinary wards and intensive care units before and during the COVID-19 pandemic: a real-life, retrospective observational study.

PURPOSE: SARS-COV-2 pandemic led to antibiotic overprescription and unprecedented stress on healthcare systems worldwide. Knowing the comparative incident risk of bloodstream infection due to multidrug-resistant pathogens in COVID ordinary wards and intensive care-units may give insights into the impact of COVID-19 on antimicrobial resistance. METHODS: Single-center observational data extracted from a computerized dataset were used to identify all patients who underwent blood cultures from January 1, 2018 to May 15, 2021. Pathogen-specific incidence rates were compared according to the time of admission, patient's COVID status and ward type. RESULTS: Among 14,884 patients for whom at least one blood culture was obtained, a total of 2534 were diagnosed with HA-BSI. Compared to both pre-pandemic and COVID-negative wards, HA-BSI due to S. aureus and Acinetobacter spp. (respectively 0.3 [95% CI 0.21-0.32] and 0.11 [0.08-0.16] new infections per 100 patient-days) showed significantly higher incidence rates, peaking in the COVID-ICU setting. Conversely, E. coli incident risk was 48% lower in COVID-positive vs COVID-negative settings (IRR 0.53 [0.34-0.77]). Among COVID + patients, 48% (n = 38/79) of S. aureus isolates were resistant to methicillin and 40% (n = 10/25) of K. pneumoniae isolates were resistant to carbapenems. CONCLUSIONS: The data presented here indicate that the spectrum of pathogens causing BSI in ordinary wards and intensive care units varied during the pandemic, with the greatest shift experienced by COVID-ICUs. Antimicrobial resistance of selected high-priority bacteria was high in COVID positive settings.

Malaria, HIV and Malnutrition among Internally Displaced People in Mozambique During COVID-19 Pandemic: Results from a Community-Based Intervention.

Background: The spread of COVID-19 poses an unprecedented challenge to care delivery in post-disaster and conflict situations. In Mozambique, the 2019 cyclone Idai and the violence by Non-State-Armed-Groups devastated the province of Sofala and Cabo Delgado respectively and led to the displacement of thousands of people living in poor and overcrowded conditions. The pandemic has further aggravated the situation. Doctors with Africa CUAMM (University college for aspiring missionary doctors) implemented surveillance activities in these regions between October 2020 and September 2021. The aim of this study is to give an overview of the prevalence of malaria, malnutrition, COVID-19 related symptoms and access to HIV testing. Methods: Data were collected in targeted internally displaced people (IDP) sites in Sofala and Cabo Delgado province between 31st January and 25th September 2021. The tool used enabled to assess COVID-19 symptoms, risk of HIV infection, malaria cases and malnutrition in children under five. Results: The project reached 93 503 people. During the study period, 13.6% people reported at least one symptom suggestive of COVID-19 infection. Malaria Rapid Diagnostic Tests (RDT) were administered to 86% of the recruited people (n = ?), with a positive diagnosis in the 4.5% of them (n = ?). Among the recruited Internally Displaced Persons (IDP), 23.1% were considered eligible for HIV screening, but only 1.4% were referred for testing. Acute malnutrition was found in 6.3% of children screened and, among these, a higher prevalence of concurrent COVID-19 symptoms was reported. Discussion: Our study highlights the importance of mass clinical screening for COVID-19 infection in this target population to enact prevention behavior, although this may not be enough, due to the pivotal role played by asymptomatic transmissions. Considering the overlap of the symptoms of COVID-19 and malaria, a combined diagnostic algorithm is urgently needed to avoid underdiagnosing malaria. Moreover, the high prevalence of respiratory symptoms in malnourished children confirmed the known correlation between malnutrition and respiratory infection. Finally, access to HIV screening needs to be implemented, given the high prevalence of people with HIV risk factors to avoid diagnostic delay. Conclusions: Population-specific needs make necessary to develop new screening methods that respond to the specific characteristics of the target population.

Human Monkeypox: A Comprehensive Narrative Review and Analysis of the Public Health Implications.

Recently, numerous cases of monkeypox were reported from several non-endemic countries in Europe, North America, and Oceania, suggesting an unusual and alarming public health issue, particularly considering that the disease is not directly related to human or animal travels. Attention is currently being drawn to this phenomenon since more than 70% of the global population is no longer vaccinated against smallpox. Indeed, the smallpox vaccination also confers some indirect degree of protection against other poxviruses, including monkeypox. We performed a narrative review to describe the existing literature with regard to monkeypox using the MEDLINE, EMBASE, and Scopus databases. This review aims to provide updated evidence of findings on the epidemiology, clinical features, diagnosis, management, and prevention of monkeypox, also considering the concurrent zoonotic pandemic caused by the COVID-19 coronavirus, SARS-CoV-2.

Impact of antimalarial resistance and COVID-19 pandemic on malaria care among pregnant women in Northern Uganda (ERASE): protocol of a prospective observational study.

BACKGROUND: Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. METHODS: In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. DISCUSSION: The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. CLINICALTRIALS: gov Identifier: NCT05348746.

Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Cefiderocol for Severe Carbapenem-Resistant A. baumannii Pneumonia: Towards the Comprehension of Its Place in Therapy.

Cefiderocol use in A. baumannii pneumonia still represents an important matter of debate. The aim of this study is to describe 13 cases of carbapenem-resistant A. baumannii (CRAB) pneumonia treated with cefiderocol in real-life practice. We retrospectively included patients with CRAB pneumonia hospitalized at Fondazione Policlinico Universitario Agostino Gemelli Hospital treated with cefiderocol either in the general ward or the intensive care unit. A total of 11 patients out of 13 had ventilator-associated pneumonia caused by CRAB, and 12/13 patients had polymicrobial infection. We found a 30-day success rate of 54%. Cefiderocol may have a role when facing severe XDR A. baumannii pneumonia. Future studies are warranted to better define its place in therapy in CRAB infections.

Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review.

Antimicrobial resistance is an urgent threat to public health and global development; in this scenario, the SARS-CoV2 pandemic has caused a major disruption of healthcare systems and practices. A narrative review was conducted on articles focusing on the impact of COVID-19 on multidrug-resistant gram-negative, gram-positive bacteria, and fungi. We found that, worldwide, multiple studies reported an unexpected high incidence of infections due to methicillin-resistant S. aureus, carbapenem-resistant A. baumannii, carbapenem-resistant Enterobacteriaceae, and C. auris among COVID-19 patients admitted to the intensive care unit. In this setting, inappropriate antimicrobial exposure, environmental contamination, and discontinuation of infection control measures may have driven selection and diffusion of drug-resistant pathogens.

Adjunctive corticosteroid treatment for organizing pneumonia in COVID-19 patients with persistent respiratory failure.

Since the beginning of COVID-19 pandemic, clinical, radiological and histopathological features consistent with viral-induced organizing pneumonia (OP) have been reported as hallmark characteristics of the disease. Here, we describe the case of ten patients with severe COVID-19 pneumonia treated with methylprednisolone 1mg/kg for showing clinical and radiological features suggestive of OP at least 20 days after symptom onset and despite standard treatment for COVID-19.

Attitudes towards Anti-SARS-CoV2 Vaccination among Healthcare Workers: Results from a National Survey in Italy.

Coronavirus disease 2019 (COVID-19) has afflicted tens of millions of people, fostering and unprecedent effort in vaccine development and distribution. Healthcare workers (HCW) play a key role in vaccine promotion and patient guidance, and it is likely that hesitancy among this population will have a major impact on the adoption of a successful immunization policy. To investigate HCW attitudes towards anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination, we developed an anonymous online cross-sectional survey. 1723 Italian HCW responded. Overall, 1155 (67%) intended to be vaccinated, while 443 (26%) were not sure and 125 (7%) declared refusal. In multivariate analysis, factors associated with hesitancy were using Facebook as the main information source and being a non-physician HCW, while predictors of acceptance included younger age, being in close contact with high-risk groups and having received flu vaccination during the 2019-2020 season. Reasons for hesitancy included lack of trust in vaccine safety (85%) and receiving little (78%) or conflicting (69%) information about vaccines. According to our results, adequate investment in vaccine education for healthcare personnel appears to be urgently needed, prioritizing non-physicians and information quality spread through social media. We hope that our data could help governments and policy-makers to target communication in the ongoing COVID-19 vaccination campaign.

Social media as a tool for scientific updating at the time of COVID pandemic: Results from a national survey in Italy.

In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources that are parallel to academic journals. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. Target of the survey were all medical figures potentially involved in the management of COVID-19 cases. 369 questionnaires were returned. 19.5% (n = 72) of respondents were younger than 30 years-old; 49,3% (n = 182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n = 42) in Intensive Care Unit and 7.4% (n = 27) were general practitioner. 70% (n = 261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update during the present pandemic, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.