Corrigendum to "Pneumocystis pneumonia in COVID-19 patients: A comprehensive review" [Heliyon 9(2) (February 2023) e13618].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13618.].

A single-center experience of early administration of tocilizumab and corticosteroids in patients with COVID-19 pneumonia.

BACKGROUND: We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after. RESULTS: The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died. CONCLUSIONS: Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

Proper death certification in the time of the COVID-19 pandemic: Forensic perspective.

It is well known that the quality of death certificates determines the accuracy of public health mortality data. In the light of a pandemic, forensic pathologists must understand the true definition of a COVID-19 death and the requirements for filling out the death certificate, as these are critical for maintaining accurate and trustworthy mortality data. To determine the scope and evolution of the COVID-19 epidemic, accurate death certification is critical. We believe that COVID-19 should be enlisted under part II or section "note" (if it exists in DC form in a particular country) of the DC in all suicide instances and putrefied bodies with positive autopsy swabs for SARS-CoV-2. In addition to our suggestions for the completion of the DC in some COVID-19 instances, we feel that forensic pathologists should follow the WHO criteria for proper DC completion in COVID-19 cases. Better physician education at this stage of the pandemic would increase adherence to existing (WHO and CDC) standards. As a result, forensic pathologists with competence in death certification could help by teaching treating physicians in this area.

Antibiotic (Mis)Use in COVID-19 Patients before and after Admission to a Tertiary Hospital in Serbia.

Antimicrobial resistance (AMR) is a global concern, and antibiotic use has risen throughout the COVID-19 pandemic. Up to 75% of COVID-19 patients are treated with antibiotics despite little evidence for their use. A retrospective study from 6 March 2020 (the start of the pandemic in Serbia) to 31 December 2021 was conducted at the Clinic for Infectious and Tropical Diseases, University Clinical Centre of Serbia. In total, 523 patients with a microbiological diagnosis of COVID-19 were included. Patient data were analysed, including antibiotic use before and after admission. Pre-admission use of antibiotics for COVID-19 treatment was documented in more than half of patients (58.1%), of which a third (34.1%) used more than one antibiotic. Macrolides, cephalosporins, and fluoroquinolones were mainly used, most frequently among patients aged between 31-45 years (75.2%). Prior antibiotic use was associated with a longer duration of illness at admission (8.8 vs. 5.7, p < 0.001), oxygen therapy upon admission (27.6% vs. 16.0%, p = 0.002), and a lower vaccination rate (60.7% vs. 50.7%, p = 0.04). When hospitalised, 72.1% of patients received antibiotics, primarily cephalosporins (71.9%). Significant efforts are needed to reduce antibiotic use in the community and improve prescribing rates by healthcare professionals.

Role and perception of clinical microbiology and infectious diseases trainees during the COVID-19 crisis.

Aim: To evaluate the role and perceptions of trainees during the COVID-19 pandemic. Method: An online survey was designed to provide an insight into the significance of the COVID-19 pandemic on working conditions of infectious diseases and clinical microbiology trainees. Results: The main roles of trainees included management of patients hospitalized for COVID-19 (55%), research (53%) and diagnostic procedures (43%). The majority (82%) of trainees felt useful in managing the crisis. However, more than two-thirds felt more stressed and more tired compared with other rotations. Only 39% of the participants had access to psychological support. Conclusion: Due to the significant impact of the pandemic on infectious diseases and clinical microbiology trainees, further research should focus on their health and welfare in the post-pandemic period.

Emerging Clinical Features of COVID-19 Related Pancreatitis: Case Reports and Review of the Literature.

INTRODUCTION: SARS-CoV-2 is fundamentally a respiratory pathogen with a wide spectrum of symptoms. The COVID-19 related pancreatitis is less considered than other clinical features. The purpose is to describe two cases of pancreatitis associated with COVID-19. METHODOLOGY: Patients' demographics, clinical features, laboratory, and instrumental findings were collected. RESULTS: Two patients admitted to the hospital were diagnosed with COVID-19 and severe acute pancreatitis, according to the Atlanta criteria. Other causes of acute pancreatitis were excluded. Treatment included broad-spectrum antibiotics, proton pump inhibitors, and low molecular weight heparin. Steroids, oxygen, antifungal treatment, and pain killers were administered when appropriate. Both patients were asymptomatic, with normal vital parameters and blood exams, and were discharged in a good condition. CONCLUSION: It is recommendable to include lipase and amylase on laboratory routine tests in order to evaluate the need for the abdominal CT-scan and specific therapy before hospital admission of the patients with COVID-19 related life-threatening acute pancreatitis.

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

SCOPE: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. SCOPE: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.

Aims and challenges of building national trainee networks in clinical microbiology and infectious disease disciplines.

Trainees represent the medical practice of tomorrow. Interactions and collaborations at the early stage in career will strengthen the future of our specialties, clinical microbiology and infectious diseases. Trainee networks at the national level help access the best education and career opportunities. The aim of this collaborative white paper between the Trainee Association of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and four national trainee networks is to discuss the motivation for building such networks and offer guidance for their creation and sustainability even during a health crisis.

COVID-19-Associated Pulmonary Aspergillosis in Patients with Acute Leukemia: A Single-Center Study.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high.

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Future developments in training.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the value of highly skilled and extensively trained specialists in clinical microbiology (CM) and infectious diseases (ID). Training curricula in CM and ID must constantly evolve to prepare trainees for future pandemics and to allow trainees to reach their full clinical and academic potential. OBJECTIVES: In this narrative review, we aim to outline necessary future adaptations in CM and ID training curricula and identify current structural barriers in training with the aim of discussing possibilities to address these shortcomings. SOURCES: We reviewed literature from PubMed and included selected books and online publications as appropriate. There was no time constraint on the included publications. CONTENT: Drawing from the lessons learnt during the pandemic, we summarize novel digital technologies relevant to CM and ID trainees and highlight interdisciplinary teamwork and networking skills as important competencies. We centre CM and ID training within the One Health framework and discuss gender inequalities and structural racism as barriers in both CM and ID training and patient care. IMPLICATIONS: CM and ID trainees should receive training and support developing skills in novel digital technologies, leadership, interdisciplinary teamwork and networking. Equally important is the need for equity of opportunity, with firm commitments to end gender inequality and structural racism in CM and ID. Policy-makers and CM and ID societies should ensure that trainees are better equipped to achieve their professional goals and are better prepared for the challenges awaiting in their fields.

Case Report: Post-mortem Histopathological and Molecular Analyses of the Very First Documented COVID-19-Related Death in Europe.

In Europe, the first case of coronavirus disease (COVID-19) and the first COVID-19-related death were reported in France on January 24th and February 15th, 2020, respectively. Officially, the first case of COVID-19 infection in the Republic of Serbia was registered on March 6th. Herein, we presented the first case of retrospective detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the post-mortem-obtained vitreous humor (VH), which took place on February 5th, 2020. This is the first death in Europe proven to be caused by COVID-19 by means of post-mortem histopathological and molecular analyses. Based on this finding, it appears that SARS-CoV-2 has been spreading faster and started spreading much earlier than it had been considered and that COVID-19 was probably the cause of the much-reported pneumonia of unknown origin in January and February 2020.

Short epidemiological overview of the current situation on COVID-19 pandemic in Southeast European (SEE) countries.

We are living in times where a viral disease has brought normal life in much of the world to a halt. The novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China initially and in a short time crossed the European borders. After mitigating the epidemic in China, Italy became one of the most COVID-19 affected countries worldwide. International travelers are important sources of infectious diseases and a possible source of epidemic. Due to its political, geographic, and cultural similarities, Italy is one of the main economic partners of Southeast European (SEE) countries. Our data show that infection in index cases in all 11 SEE countries was travel-related with Italy being a source country for 8/11 countries. After the first case identifications on February 25, the number of cases in SEE countries is continually rising reaching the total number of 15,612 with 565 fatal cases and overall case fatality ratio (CFR) of 3.6 (median 3.8, range 0.8-5.5) by April 10, 2020. At a time when the COVID-19 pandemic is approaching its peak, apart from the problems with treatment of the disease and care for critically ill patients, there are other equally important problems, such as organization of outbreak response, provision of health care, lack of hospital personnel, disruption of personal protective equipment supply chains and health care workers (HCWs) protection. But what is more important is the heroic behavior of the HCWs who are showing their humanity by disregarding their lives.