Infectious Units Research Articles

Unpacking the Complexity of COVID-19 Fatalities: Adverse Events as Contributing Factors-A Single-Center, Retrospective Analysis of the First Two Years of the Pandemic.

In a retrospective analysis of 477 fatal COVID-19 cases hospitalised at a single medical centre during the period from 6 March 2020 to 30 June 2022, several factors defining those patients at admission were assessed, as well as the course of the hospitalisation and factors contributing to death. There was a predominance of men (59.3% (283)) burdened by comorbidities, with increased inflammation at admission. Patients aged ≥ 81 years were significantly more likely to be admitted to and die in infectious diseases units (IDU) due to respiratory failure, their hospital stays were shorter, and they were most likely not to receive specialist treatment. The most common COVID-19 complications included acute kidney injury in 31.2% (149) patients and thromboembolic complications in 23.5% (112). The course of hospitalisation was complicated by healthcare-associated infections (HAI) in 33.3% (159) of cases, more often in those treated with baricitinib (p < 0.001). The initial use of an antibiotic, although common (94.8% (452)), was unwarranted in almost half of the cases (47.6% (215)). Complications of hospitalisation (46.1% (220)) and adverse events involving staff (49.7% (237)) were found in almost half of the patients. In 88.7% (423) of the cases, death was due to respiratory failure in the course of SARS-CoV-2 infection. Adverse events during hospitalisation should be considered as an additional factor that, in addition to the infection itself, may have influenced the death of patients.

P14 Surgical source control and colistin therapy for the management of osteomyelitis due to Pseudomonas aeruginosa with difficult-to-treat resistance

Abstract Patient A 45-year-old man from Lagos, Nigeria, now living in the UK, presented to his local hospital with purulent discharge from his knee. During a road traffic accident in 2019, he had sustained open fractures of his femur and tibia. These required surgical fixation and he underwent four surgeries over a 10-month period in Nigeria. He was reportedly on antibiotics throughout this period. In early 2022, he noticed discharge from the knee and was referred to the Bone Infection Unit in Oxford. On examination, left leg shortening and a sinus on the anterior proximal tibia were noted. Knee flexion was reduced to 30 degrees. He was otherwise systemically well. PET-CT revealed two areas of avidity, supporting the clinical diagnosis of fracture-related infection adjacent to a retained tibial plate. Treatment The patient underwent removal of the tibial plate, excision of infected bone, insertion of local antibiotic carrier (Cerament G with vancomycin added) and a medial gastrocnemius flap with split skin grafting. Five out of five intra-operative samples were culture positive for Pseudomonas aeruginosa, with NDM metallo-β-lactamase detected. This was resistant to ceftazidime, meropenem, piperacillin/tazobactam, gentamicin, tobramycin, amikacin, ciprofloxacin, ceftazidime/avibactam, imipenem/cilastatin/relebactam, ceftolozane/tazobactam and cefiderocol. The organism had an aztreonam MIC of 16 mg/mL and a colistin MIC of 2 mg/mL. The patient also had MRSA isolated from all intra-operative samples. Following multidisciplinary team discussion, he was started on aztreonam 2 g QDS and colistin loading with 9 million IU followed by 4.5 million IU BD for the P. aeruginosa and doxycycline 100 mg BD for the MRSA. After 8 days of therapy, he developed a symmetrical body rash, which was felt to be a delayed hypersensitivity reaction to aztreonam and resolved when aztreonam was stopped. He was subsequently treated with colistin monotherapy for 6 weeks via OPAT. Whilst on this treatment, his renal function was monitored regularly with appropriate dose reductions because of renal impairment. Follow-up at 9 months demonstrates good recovery with no pain or symptom recurrence. Conclusions This case illustrates the challenges of managing fracture-related infections with extensively drug-resistant organisms and the importance of multi-disciplinary input. Drug-resistant infections requiring prolonged courses of antibiotics can be successfully managed using an OPAT service. Finally, this case emphasizes the importance of understanding global patterns of antimicrobial resistance and stewardship to identify cases that are at risk of being infected with drug-resistant bacteria especially where there may be long intervals between establishment of the infection and presentation to healthcare services.

An end-point multiplex PCR/reverse transcription-PCR for detection of five agents of bovine neonatal diarrhea

Neonatal calf diarrhea (NCD) is frequently associated with single or mixed viral, bacterial and/or protozoal infections. Consequently, laboratory diagnostic of NCD usually requires specific tests for each potential agent; a time-consuming, laborious and expensive process. Herein, we describe an end-point multiplex PCR/reverse transcription-PCR (RT-PCR) for detection of five major NCD agents: bovine rotavirus (BRV), bovine coronavirus (BCoV), Escherichia coli K99 (E. coli K99), Salmonella enterica (S. enterica) and Cryptosporidium parvum (C. parvum). Initially, we selected and/or designed high-coverage primers. Subsequently, we optimized multiplex PCR/RT-PCR conditions. Next, we evaluated the analytical sensitivity of the assay and assessed the performance of the reaction by testing 95 samples of diarrheic calf feces. The analytical specificity was evaluated against bovine viral diarrhea virus (BVDV), E. coli heat-stable enterotoxin (STa) and Eimeria spp. The detection limit of our assay was about 10 infectious units of BRV, 10−2 dilution of a BCoV positive sample pool, about 5 × 10−4 CFU for S. enterica, 5 × 10−6 CFU for E. coli K99 and 50 oocysts for C. parvum. No non-specific amplification of other bovine diarrhea agents was detected. Out of 95 samples analyzed, 50 were positive for at least one target, being 35 single and 15 mixed infections. BRV was the most frequent agent detected in single infections (16/35), followed by Cryptosporidium spp. (11/35), which was the most frequent in mixed infections (11/15). Positive and negative multiplex results were confirmed in individual reactions. In conclusion, we described an end-point multiplex PCR/RT-PCR for faster and easier NCD diagnosis, which may be useful for routine diagnosis and surveillance studies.

Imagining the next pandemic: Finnish preparedness for chronic transboundary crises before and during COVID‐19

AbstractBefore the COVID‐19 pandemic, infectious disease experts had postulated that the next pandemic is only a matter of time, and Finland, among other nations, had prepared for it. Yet the COVID‐19 pandemic crossed the customary political, functional, and temporal boundaries of crisis management to a surprising degree. This study analyses pandemic preparedness among Finnish infectious disease experts at the central government level before and during the COVID‐19 pandemic (2017–2021). The study is based on interview material, participant observation in the Finnish Institute for Health and Welfare's infectious disease unit in 2017, and health security‐related document analysis. By analyzing expert perceptions of preparedness in two points of time, the study provides insights on the challenges that increasingly transboundary crises have posed for preparedness efforts. The experts perceived that pandemic preparedness would benefit from a more generic approach to planning and from more comprehensive risk assessments and policy advice. The analysis shows that Finnish crisis management had overlooked the extent of transboundedness of present‐day crises and is lacking consideration of how crises turn into chronic conditions that deplete capacities over time. The crisis man.agement regime needs to develop structures to better analyze systemic risks and to extend its timeframe to cover long‐term crises.

Development of a CRISPR-Cas12a rapid diagnostic for human cytomegalovirus

Despite decades of research, human cytomegalovirus (CMV) continues to contribute to significant morbidity and mortality in transplant settings and remains the leading cause of viral congenital infections. Clinical diagnosis of CMV infection and/or reactivation under these settings is completed using real time quantitative polymerase chain reaction (RT-qPCR). This assay performs well but is hampered by poor sensitivity and a lack of standardization among testing facilities. A point-of-care rapid diagnostic to determine CMV viremia could address these issues and improve patient care. In this manuscript, we introduce clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a technology to design and validate a rapid diagnostic for CMV. This system was tested using CMV spiked human saliva and urine samples. Sensitivity of the assay was ∼10 infectious units (IU)/mL. Specificity of the assay was robust and failed to detect other herpesviruses. Collectively, we have designed and validated a rapid diagnostic for CMV that overcomes limitations of the current standard diagnostic. This assay has the potential to be used as a point-of-care screening tool in transplant and neonatal settings.

Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab.

A growing number of evidences suggest that the combination of hyperinflammation, dysregulated T and B cell response and cytokine storm play a major role in the immunopathogenesis of severe COVID-19. IL-6 is one of the main pro-inflammatory cytokines and its levels are increased during SARS-CoV-2 infection. Several observational and randomized studies demonstrated that tocilizumab, an IL-6R blocker, improves survival in critically ill patients both in infectious disease and intensive care units. However, despite transforming the treatment options for COVID-19, IL-6R inhibition is still ineffective in a fraction of patients. In the present study, we investigated the impact of two doses of tocilizumab in patients with severe COVID-19 who responded or not to the treatment by analyzing a panel of cytokines, chemokines and other soluble factors, along with the composition of peripheral immune cells, paying a particular attention to T and B lymphocytes. We observed that, in comparison with non-responders, those who responded to tocilizumab had different levels of several cytokines and different T and B cells proportions before starting therapy. Moreover, in these patients, tocilizumab was further able to modify the landscape of the aforementioned soluble molecules and cellular markers. We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.

The Isolation System for Treatment and Agile Response for High-Risk Infections (ISTARI) Unit, a Carecubes Design: Moving PPE Around the Patient, An Assessment of Provider Safety and Infection Control with Emergency Medicine Residents During Simulation

Introduction:The ISTARI unit is designed to be assembled in buildings or field hospitals to provide negative-pressure rooms in low-resource areas and decrease PPE use in the setting of highly-infectious diseases. Each unit is designed to perform ~20 air exchanges/hour with HEPA filters with multiple access points for providers to perform patient care without entering the unit while decreasing overall PPE usage. The goals of the design include patient safety, ease of use for, decreased infectious spread, and unit affordability.Method:A survey was obtained following a medical simulation within the ISTARI unit with Emergency Medicine resident physicians. The case involved an Ebola patient with Ventricular Tachycardia which progressed to cardiac arrest. Teams were given written and video instructions for the ISTARI unit and Ebola-level PPE. They were limited to one set of high-level PPE for the case. The survey scoring was a 0-5 scale, five being the highest.Results:Medical history-taking provider safety (PS)- 2.87, infection control (IC)-3.09, physical examination PS-3.52, IC-3.78, ultrasound usage PS-3.35, IC-3.43, intubation PS-2.35, IC-2.57, CPR PS-3.43, IC-3.65, cardioversion PS-3.35, IC-3.78, and overall average PS-3.145, IC-3.383.Limitations were noted compared with traditional care, but 100% of teams met critical actions for patient management, including intubation, cardioversion, and CPR. GloGerm showed no contamination to those providing care outside the unit, but a small amount of contamination after doffing for those who entered the unit.Conclusion:The ISTARI unit is a cost-effective isolation unit maximizing provider safety in management of patients with highly-infectious diseases, particularly in low-resource settings. It allows for easy mobilization of units and decreased medical supplies waste. The preliminary study shows satisfactory data about provider safety and infection control when using ISTARI for a highly-infectious patient, especially in providers unfamiliar with typical high-level PPE. Providers were able to provide all necessary critical actions for highly-infectious, critically-ill patients.

Recombinant Virus Quantification Using Single-Cell Droplet Digital PCR: A Method for Infectious Titer Quantification.

The quantification of viruses is necessary for both research and clinical applications. The methods available for RNA virus quantification possess several drawbacks, including sensitivity to inhibitors and the necessity of a standard curve generation. The main purpose of this study was to develop and validate a method for the quantification of recombinant, replication-deficient Semliki Forest virus (SFV) vectors using droplet digital PCR (ddPCR). This technique demonstrated stability and reproducibility using various sets of primers that targeted inserted transgenes, as well as the nsP1 and nsP4 genes of the SFV genome. Furthermore, the genome titers in the mixture of two types of replication-deficient recombinant virus particles were successfully measured after optimizing the annealing/extension temperature and virus:virus ratios. To measure the infectious units, we developed a single-cell ddPCR, adding the whole infected cells to the droplet PCR mixture. Cell distribution in the droplets was investigated, and β-actin primers were used to normalize the quantification. As a result, the number of infected cells and the virus infectious units were quantified. Potentially, the proposed single-cell ddPCR approach could be used to quantify infected cells for clinical applications.

Visits to Sexually Transmitted Infection Clinics in Italy from January 2016 to November 2021: A Multicenter, Retrospective Study.

There is no evidence of seasonal variation in visits to clinics dedicated to sexually transmitted infections (STIs) in Italy, nor of changes after the advent of the COVID-19 pandemic. An observational, retrospective, multicentric study was conducted to record and analyze all the visits to the STI clinics of the Dermatology Units of the University Hospitals of Ferrara and Bologna and of the Infectious Disease Unit of Ferrara, Italy, between January 2016 and November 2021. Overall, 11.733 visits were registered over a 70-month study period (63.7% males, mean age 34.5 ± 12.8 yrs). The mean number of monthly visits significantly decreased from the advent of the pandemic (136) compared to before (177). In the pre-pandemic period, visits to STI clinics increased in the autumn/winter months when compared to spring/summer, while the trend was the opposite in the pandemic period. Thus, during the pandemic, both an overall significant reduction in visits to STI clinics and a reversal in their seasonality were observed. These trends affected males and females equally. The marked decrease, mostly found in the pandemic winter months, can be linked to the "lockdown"/self-isolation ordinances and social distancing measures during the colder months, coinciding with the spread of the COVID-19 infection, which limited the opportunities for meeting and socializing.

Hepatitis E-associated neuralgic amyotrophy: a rare respiratory presentation.

Hepatitis E-associated neuralgic amyotrophy: a rare respiratory presentation.

Duration of antibiotic treatment and timing of oral switching for bloodstream infections: a survey on the practices of infectious diseases and intensive care physicians

This study was designed to understand current practice in duration of antibiotic treatment and timing of intravenous (iv) to oral switch for common bacteraemic conditions amongst infectious diseases (ID) and intensive care unit (ICU) physicians. An online survey consisting of 18 questions comprising five common clinical bacteremia scenarios (adapted from the original survey designed by University of Toronto (Toronto, Ontario, Canada)) was conducted amongst Turkish ID and ICU physicians between November 2020 and November 2021. A total of 236 physicians (76.5 % ID and 17.5 % ICU) responded. The most commonly recommended duration for bacteremia was 14 days (42%), followed by 10 (27%) and 7 (18%) days. The median (IQR) recommended durations were 10 (10-14) days for central venous catheter associated bloodstream infection, 10 (7-14) days for bacteraemic pneumonia, 14 (10-14) days for bacteraemic urinary tract and intraabdominal infections, and 14 days (7-14) for bacteraemic skin and soft tissue infection. Carbapenem resistance but not pathogen type influenced the recommendations. There was not a significant difference in responses for most scenarios between ID and ICU physicians. A switch to oral antibiotics after a median duration of 7 (IQR 5-7) days of iv treatment was considered by 80% of respondents. Prolonged treatment was recommended for most clinical scenarios. Extended iv durations were recommended before oral switch. A presumption that resistant bacterial infections require longer therapy may be responsible for prolonged treatment durations.

Mycoplasma genitalium antibiotic resistance-associated mutations in genital and extragenital samples from men-who-have-sex-with-men attending a STI clinic in Verona, Italy.

Mycoplasma genitalium (MG) is one of the most warning emerging sexually transmitted pathogens also due to its ability in developing resistance to antibiotics. MG causes different conditions ranging from asymptomatic infections to acute mucous inflammation. Resistance-guided therapy has demonstrated the best cure rates and macrolide resistance testing is recommended in many international guidelines. However, diagnostic and resistance testing can only be based on molecular methods, and the gap between genotypic resistance and microbiological clearance has not been fully evaluated yet. This study aims at finding mutations associated with MG antibiotic resistance and investigating the relationship with microbiological clearance amongst MSM. From 2017 to 2021, genital (urine) and extragenital (pharyngeal and anorectal swabs) biological specimens were provided by men-who-have-sex-with-men (MSM) attending the STI clinic of the Infectious Disease Unit at the Verona University Hospital, Verona, Italy. A total of 1040 MSM were evaluated and 107 samples from 96 subjects resulted positive for MG. Among the MG-positive samples, all those available for further analysis (n=47) were considered for detection of mutations known to be associated with macrolide and quinolone resistance. 23S rRNA, gyrA and parC genes were analyzed by Sanger sequencing and Allplex™ MG and AziR Assay (Seegene). A total of 96/1040 (9.2%) subjects tested positive for MG in at least one anatomical site. MG was detected in 107 specimens: 33 urine samples, 72 rectal swabs and 2 pharyngeal swabs. Among them, 47 samples from 42 MSM were available for investigating the presence of mutations associated with macrolide and quinolone resistance: 30/47 (63.8%) showed mutations in 23S rRNA while 10/47 (21.3%) in parC or gyrA genes. All patients with positive Test of Cure (ToC) after first-line treatment with azithromycin (n=15) were infected with 23S rRNA-mutated MG strains. All patients undergoing second-line moxifloxacin treatment (n=13) resulted negative at ToC, even those carrying MG strains with mutations in parC gene (n=6). Our observations confirm that mutations in 23S rRNA gene are associated with azithromycin treatment failure and that mutations in parC gene alone are not always associated with phenotypic resistance to moxifloxacin. This reinforces the importance of macrolide resistance testing to guide the treatment and reduce antibiotic pressure on MG strains.

An exploratory prospective study of the factors associated with adverse health outcomes in older adults living with HIV.

This study examines the clinical and sociodemographic factors associated with adverse health outcomes (falls, emergency room visits, hospital admissions and death) in a cohort of patients older than 55 years with HIV infection. It is an exploratory prospective study with four years follow-up. People with HIV infection followed in the infectious diseases consultation unit of two hospitals in Madrid were included. Sociodemographic data and clinical variables were collected. The functional, mental, and social situations of the participants were assessed. Patient clinical histories were reviewed to gather data on the number of falls, visits to emergency departments and hospital admissions during the period studied. One hundred seventeen patients with a mean age of 61,4 (SD 6,6) years and a median follow-up of 47 months(35 to 50) were included. Of these subjects, 25% had depressive symptoms, and 10% had some degree of cognitive impairment at the baseline visit. The recorded frequencies were: falls 7,7%, visits to the emergency room 53%, hospital admission 33,3% and deaths 2,6%. Depressive symptoms were associated with falls and emergency room visits in the univariate analysis. The factors associated with hospital admission were having acquired the infection through intravenous drug use, frailty and being under 65 years of age. Multivariate analysis was conducted for the hospital admissions outcome, with the variables showing p < 0,07 in the univariate analysis, none of which reached statistical significance. Depression screening and cognitive evaluation should be done systematically in this population group. More studies with more patients and longer follow-up times are necessary.

Canine Coronavirus Infection Modulates the Biogenesis and Composition of Cell-Derived Extracellular Vesicles.

Coronavirus (CoV) has persistently become a global health concern causing various diseases in a wide variety of hosts, including humans, birds, and companion animals. However, the virus-mediated responses in animal hosts have not been studied extensively due to pathogenesis complexity and disease developments. Extracellular vesicles (EVs) are widely explored in viral infections for their intercellular communication, nanocarrier, and immunomodulatory properties. We proposed that coronavirus hijacks the host exosomal pathway and modulates the EV biogenesis, composition, and protein trafficking in the host. In the present study, Crandell-Rees feline kidney (CRFK) cells were infected with canine coronavirus (CCoV) in an exosome-free medium at the multiplicity of infection (MOI) of 400 infectious units (IFU) at various time points. The cell viability was significantly decreased over time, as determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Post-infection EVs were isolated, and transmission electron microscopy (TEM) showed the presence of small EVs (sEVs) after infection. NanoSight particle tracking analysis (NTA) revealed that EV sizes averaged between 100 and 200 nm at both incubation times; however, the mean size of infection-derived EVs was significantly decreased at 48 h when compared to uninfected control EVs. Quantitative analysis of protein levels performed by dot blot scanning showed that the expression levels of ACE-2, annexin-V, flotillin-1, TLR-7, LAMP, TNF-α, caspase-1, caspase-8, and others were altered in EVs after infection. Our findings suggested that coronavirus infection impacts cell viability, modulates EV biogenesis, and alters cargo composition and protein trafficking in the host, which could impact viral progression and disease development. Future experiments with different animal CoVs will provide a detailed understanding of host EV biology in infection pathogenesis and progression. Hence, EVs could offer a diagnostic and therapeutic tool to study virus-mediated host responses that could be extended to study the interspecies jump of animal CoVs to cause infection in humans.

Upper gastrointestinal bleeding in adults treated with veno-arterial extracorporeal membrane oxygenation: a cohort study.

Upper gastrointestinal bleeding is a common complication in adults treated with veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) for refractory cardiogenic shock or cardiac arrest. We aimed to determine risk factors, prevalence and outcomes associated VA-ECMO-associated upper gastrointestinal bleeding (UGIB) in adult patients. We conducted a retrospective cohort study (2014-2022) on consecutive VA-ECMO patients in the Medical and Infectious Disease intensive care unit of university hospital Bichat-Claude Bernard in Paris, France. UGIB was defined as 1) an overt bleeding (hematemesis, melena, hematochezia), or 2) acute anemia associated with a lesion diagnosed on upper gastrointestinal endoscopy. VA-ECMO-associated UGIB was defined as an UGIB occurring during VA-ECMO, or up to ten days after decannulation in patients weaned-off ECMO. Cause-specific models were used to identify factors associated with UGIB and death, respectively. Among the 455 patients included, 48 (10%) were diagnosed with UGIB after a median of 12 [7; 23] days following ECMO cannulation. Mortality occurred in 36 (75%) patients with UGIB and 243 (60%) patients without. UGIB patients had longer ICU stays (32 [19; 60] vs 18 [7; 37] days; p<.01), longer ECMO (14 [9; 18] vs 7 [4; 11] days; p <.01) and mechanical ventilation durations (21 [16; 36] vs. 10 [5; 20] days; p <.01), as compared to non-UGIB patients. Ninety upper gastrointestinal endoscopies (UGE) were performed, and the most frequent lesions detected were gastro-duodenal ulcers (n = 23, 26%), leading to 11/90 therapeutic procedures. By multivariable analysis, a history of peptic ulcer (Cause-specific hazard ratio (CSHR) 2.93, 95%CI 1.01; 8.51), a dual antiplatelet therapy (CSHR 2.0, 95%CI 1.07; 3.72]) and extracorporeal cardiopulmonary resuscitation (ECPR) (CSHR 2.78, 95%CI 1.42; 5.45) were independently associated with an increased risk of UGIB. In adult patients under VA-ECMO, a history of gastric ulcer, dual antiplatelet therapy and ECPR were independently associated with an increased risk of UGIB. This study highlights the potential role of acute ischemia reperfusion injury in the pathophysiology of VA-ECMO-associated UGIB.

All-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone: a prospective cohort study

ObjectivesTo study the mortality of patients with COVID-19 in Sierra Leone, to explore the factors associated with mortality during the COVID-19 pandemic and to highlight the complexities of treating patients...

Logistical challenges with an emphasis on organizing specialized triage in the conditions of a newly emerging, epidemiologically significant infectious pathogen for humans – SARS-CoV2

Background: UMHATEM „N.I. Pirogov“ Sofia, is one of the largest and busiest hospitals for emergency medical care in Bulgaria. It is the legal successor of the former Institute of Emergency Medicine „N.I. Pirogov“, and it can be said that at the moment it is the only diagnostic- therapeutic, prophylactic and scientific-educational structure of this type within the Bulgarian healthcare system. The concept of adequate functioning and development of this type of hospital does not consider structuring an Infectious Diseases diagnostic-treatment unit. This reality makes necessary the formation of a radically different organization for the admission and treatment of patients in the hospital, both for those with symptoms of Covid 19 and for all other emergency patients. The organization created in this way must absolutely guarantee safety for both streams of patients. In the conditions of a pandemic, in case of a real threat to public health, the main task of triage in the Emergency Department is to establish indications for urgent hospitalization, or to refuse it in the absence of indications. The characteristic course of the disease, the prolonged treatment, the manifestations within the so-called „post-Covid syndrome“, require serious planning not only of the diagnostic-treatment and rehabilitation period, but also adequate monitoring in the first months after the patient‘s discharge. Within the national reorganization measures, during the determined periods, the main changes concerning the MED (Multi-profile emergency department) of Pirogov are implemented, with an emphasis on the formation of a specialized triage for the diagnosis and clinical evaluation of patients with a coronavirus infection. The main goal is the adequate diagnosis, treatment and follow-up of patients with coronavirus infection who have passed through the organized Covid-triage in a period of extreme pressure on the emergency structures and on the hospital system in the country as a whole. Objective: For a MED, which at the time of declaring an epidemic situation does not have a concept for the diagnosis and treatment of infectious diseases, to systematize the main urgently implemented organizational and structural changes, which turned out to be absolutely necessary to meet a newly emerging epidemiologically significant infectious disease. Aims: To systematize the organizational changes imposed by the situation and urgently implemented in the MED (multi-profile emergency department). To systematize the structural changes imposed by the situation and urgently implemented in the work of the MED. To analyze the organizational and structural changes carried out in this way and to differentiate the main difficulties caused by the regulations existing at the time of the announcement of the epidemic situation.

NEW APPROACHES TO ECOSYSTEMIC STUDY OF ANIMALS (BIRDS) POPULATION HEALTH UNDER CONDITIONS OF THE NORTH-WESTERN REGION OF THE RUSSIAN FEDERATION

The purpose of our research was to study the formation, functioning and structure of the nosological profile of infectious and invasive pathology of animals (birds) under conditions of the NorthWestern Region of the Russian Federation, to identify the main nosological units that form the epizootic and epidemic risk in the region and based on this to justify and determine the priority of measures for optimisation the anti-epizootic support of poultry farming in the region. In modern veterinary and biological sciences, there had been formed a concept about systemic understanding of ecologization in epizootology and epidemiology. A holistic scientific concept about the infectious parasitic system and self-regulation of the epizootic process of infectious and invasive parasitic systems had been formed (V. D. Belyakov et al., 1987). The notions "infection" and "infectious disease" are full-fledged components of parasitism (I. A. Bakulov, 1997; V. V. Sochnev, 1997; V. P. Urban, 1997; V. V. Makarov, 2022). In global epizootology the global epizootological category had been formulated – epizootological parameters of animals population, including population health, population reproduction, its economic utility and epidemic danger (V. V. Makarov, V. V. Sochnev, O. V. Kozyrenko, 2022; V. V. Sochnev, Yu. V. Pashkina, 2019). Animals health level largely depends on comfortness of the environment for their organisms, on epizootic safety of the territories, on the sustainability of ecological niche of parasitic systems pathogens and their epizootological geography. In the paper the animals infectious pathology nosological profile is studied under conditions of the North-Western Region of the Russian Federation, under conditions of a metropolis and its suburbs. The ecological niche of disease pathogens, its dependence on density axis and on host populations diversity were measured in quantities. It was discovered that the territorial boundaries for epizootic manifestation of the animals (birds) infectious pathology nosological units in the region tend to be formed under multifactorial influence, one of the main factors being the formation of the ecological niche of pathogens. In the North-Western Region the animals (birds) infectious pathology was formed from bacterioses in 11.49 %, from virosis in 12.4 %, from mycoses in 2.46 % and from invasive units in 73.6 %. The parasitic diseases of the ecosystem and their monoand polyhost epizootic manifestation were studied; the involvement of productive and unproductive animals populations co-members in the parasitic systems functioning was analysed; animals (birds) infectious pathologies dominating in the region were identified and the visualization of dominance semiotics of the specific nosological units was achieved by constructing Pareto diagrams.

Addition of Baricitinib to Usual Therapeutic Regimen in Hospitalized Patients with Severe Covid-19: A Prospective Cohort Study

Background-Purpose: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected our everyday lives for the last three years, leading to in numerous patient hospitalizations all over the world and a plethora of therapeutic interventions being implemented in an effort to combat the disease. Baricitinib is an oral selective Janus kinase (JAK) inhibitor approved for the treatment of rheumatic disease that was hypothesized to bear positive effect on the more severe forms of the novel coronavirus disease 2019 (COVID-19) based on its antiviral and anti-cytokine properties. The purpose of the current prospective cohort study was to study the effect of adding baricitinib to the usual drug regimen of patients hospitalized with severe COVID-19 in the infectious disease unit of a third-level hospital. Patients-Methods: The current prospective cohort study was conducted at the Infectious Disease Unit of the 401 General Military Hospital of Athens, recruiting a total of 74 patients who were hospitalized with severe COVID-19 based on the COVID-19 severity index. Relevant demographic data, personal and family medical history and turnout of the cases was documented. Laboratory examinations as well as arterial blood gases (ABGs) were recorded and analysed both upon admission and discharge of the patients. An oral dose of 4 mg baricitinib daily (or an adjusted dose of 2 mg daily in cases of renal disease) was added to the usual therapeutic regimen of the patients. Results: For the purpose of the current study, we recruited 74 patients (male sex 81.1%, mean age 52,8±17,2 years old). Six patients (8.1%) were fully vaccinated and 32 patients (43.2%) presented at least one comorbidity (chronic cardiovascular disease, chronic liver disease, chronic kidney disease, immunosuppression, diabetes mellitus or obesity). Mean hospitalization time reached 10.9 ± 5.8 days while mean time of baricitinib administration was 9.2 ± 2.9 days. Regarding outcomes of hospitalizations, 12 patients (16.2%) needed to be transferred to the intensive care unit (ICU), with 6 of them finally succumbing to the disease. Administration of the drug led to a statistically significant drop of inflammatory markers as well as a statistically significant improvement of respiratory function as evaluated by ABGs. No serious adverse events were recorded. Conclusion: The addition of oral baricitinib to the standard drug regimen of hospitalized patients with severe COVID-19 proved safe and efficacious in managing symptoms of the disease, leading to swift clinical complaint and laboratory profile improvements.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy

BackgroundThere is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. ObjectiveThis study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. MethodsAn observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. ResultsMale patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. ConclusionsStatistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.