Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

Sex differences and disparities in cardiovascular outcomes of COVID-19.

AIMS: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. METHODS AND RESULTS: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04). CONCLUSIONS: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients-An Open-Label Phase II Clinical Trial.

Background: COVID-19 convalescent plasma (CCP) is an important antiviral option for selected patients with COVID-19. Materials and Methods: In this open-label, phase 2, clinical trial conducted from 30 April 2020 till 10 May 2021 in the Republic of North Macedonia, we evaluated the efficacy and safety of CCP in hospitalized patients. Treatment was with a single unit of CCP having an anti-RBD IgG concentration higher than 5 AU/mL. Results: There were 189 patients that completed the study, of which 65 (34.4%) had WHO 8-point clinical progression scale score of 3 (requiring hospital care but not oxygen support), 65 (34.4%) had a score of 4 (hospitalized and requiring supplemental oxygen by mask or nasal prongs), and 59 (31.2%) had a score of 5 (hospitalized and requiring supplemental oxygen by non-invasive ventilation or high-flow oxygen). Mean age was 57 years (range 22−94), 78.5% were males, 80.4% had elevated body mass index, and 70.9% had comorbidity. Following CCP transfusion, we observed clinical improvement with increase rates in oxygenation-free days of 32.3% and 58.5% at 24 h and seven days after CCP transfusion, a decline in WHO scores, and reduced progression to severe disease (only one patient was admitted to ICU after CCP transfusion). Mortality in the entire cohort was 11.6% (22/189). We recorded 0% mortality in WHO score 3 (0/65) and in patients that received CCP transfusion in the first seven days of disease, 4.6% mortality in WHO score 4 (3/65), and 30.5% mortality in WHO score 5 (18/59). Mortality correlated with WHO score (Chi-square 19.3, p < 0.001) and with stay in the ICU (Chi-square 55.526, p ≤ 0.001). No severe adverse events were reported. Conclusions: This study showed that early administration of CCP to patients with moderate disease was a safe and potentially effective treatment for hospitalized COVID-19 patients. The trial was registered at clinicaltrials.gov (NCT04397523).

Evaluation of oxidative stress markers in hospitalized patients with moderate and severe COVID-19.

Background. Clinical evidence suggests increased oxidative stress in COVID-19 patients and this worsened redox status could potentially contribute to the progression of the disease. Objectives. To investigate the oxidative stress we have measured oxidative stress parameters, namely, PAT (total antioxidant power, iron reducing) and d-ROMs (plasma peroxides). Additionally we have investigated their correlation with the most frequently used clinical parameters CRP, LDH, and NLR in serum from moderate and severe COVID-19 patients hospitalized in a tertiary hospital. Methods. PAT and d-ROMs were determined by analytical photometric metric method in serum from 50 hospitalized patients. For each of them, two samples were collected and analyzed immediately after collection seven days apart. Results. All patients at admission had a much higher value for plasma peroxides and a significant correlation between oxidative stress parameters and CRP, LDH, and NLR. (p<0.05), except for OS index (OSI) vs CRP in the severe group. At discharge, plasma peroxides were reduced and OSI was improved in the moderate group. Conclusion. We consider that using OSI at the beginning of COVID-19 disease presents a valuable starting point for the general assessment of oxidative stress and hence enabling a better triage of the patients in terms of disease severity.

Insight in the Current Progress in the Largest Clinical Trials for Covid-19 Drug Management (As of January 2021).

The outbreak of the COVID-19 pandemic has generated the largest global health crisis of the 21st century, evolving into accelerating socioeconomic disruption. In spite of all rapidly and widely emerging scientific data on epidemiology, diagnosis, prevention and treatment of the COVID-19 disease, severe acute respiratory coronavirus 2 (SARS-CoV-2) is continuing to propagate in lack of definitive and specific therapeutic agents. Current therapeutic strategies are mainly focused on viral inhibition by antiviral drugs and hampering the exuberant immune response of the host by immunomodulatory drugs. In this review, we have studied the reports of the largest clinical trials intended to COVID-19 treatment published during the first year of the pandemics. In general, these results concentrate on seven therapeutic options: remdesivir, chloroguine/hydroxychloroquine, lopinavir-ritonavir combination, corticosteroids, tocilizumab, convalescent plasma and monoclonal antibodies. In line with the reviewed data, as of January 2021, most of the evidence support the use of remdesivir in hospitalized patients with moderate and severe forms of the disease and provide reliable data on the substantial beneficial effect of corticosteroids in patients requiring supplemental oxygen. Moreover, preliminary RECOVERY trial results have demonstrated the efficacy of tociluzumab in the treatment of critically ill patients. The reports presenting the outcomes of the other immune-based therapies under investigation are enthusiastically awaited.

The Impact of Pneumonia on the Course and Outcome in Patients with Seasonal Influzenza.

INTRODUCTION: Seasonal influenza, although often presented as a mild, self-limiting disease, is frequently accompanied by complications that lead to the development of a severe clinical presentation and a fatal outcome. The most common are respiratory complications, with secondary bacterial pneumonia being the leading cause. AIM: The aim of this study is to determine the impact of pneumonia on the severity of the clinical presentation and outcome in patients with seasonal influenza. MATERIALS AND METHODS: This research is comparatively group-based and has been conducted at the University Clinic for Infectious Diseases and Febrile Conditions during a three-year period. The analysis consists of 122 adult patients with clinically and laboratory-confirmed influenza. Based on the severity of the clinical picture, the patients are divided into two groups, severe (n=87) and mild (n=35) forms of the disease. The study included demographic, general data, clinical symptoms, and signs as well as complications. RESULTS: Of 122 patients with seasonal influenza, complications were registered among 108(88.52%), with a significantly more frequent emergence among the group with severe influenza 93.1% vs 77.14% (p=0.012). Pneumonia was the most common 98(80.33%) and had a significant effect on disease severity (p=0.002). Complications from the types of ABI 8(6.56%), ARDS 7(5.74%), sepsis 5(4.1%), DIC 4 (3.28%) and otitis 2(1.64%) were reported only in the group with severe influenza. Acute meningoencephalitis was registered among 5(4.1%), gastroenterocolitis among 3(2.46%), and hepatic damage among 14(11.47%) of patients. CONCLUSION: Pneumonia as the most common complication among patients with seasonal influenza significantly impacts the clinical course and outcome of the illness.

Prevalence of Rotaviruses in the Etiology of Acute Diarrhea in Young Children, Clinical forms, Extraintestinal Manifestations and Complications.

Rotavirus is highly contagious factor with dominant feces-oral transmission. Because it is stable in external environment, transmission clusters are possible by close contact, ingestion of contaminated water or food or contact with contaminated surfaces. It survives within hours and days on hands and contaminated surfaces. This makes it the most common enteric and nosocomial pathogen in the world, especially in early childhood. In addition to the rapid dehydration with pronounced electrolyte disturbances, numerous extraintestinal possibilities have been recorded in the clinical picture, which emphasizes the need for prevention of this disease.In the period from 1.02.2018 to 31.01.2020 at the Clinic for Infectious diseases were treated 1060 patients with diarrheal disease, of which 502 children (47.36%). Rotavirus etiology was confirmed in 23.30% of the children. According to the protocols, laboratory and biochemical investigations were done to all 117 children, with tracking parameters and their dynamics of admission and discharge from the hospital. Most of the children, 84 (82.0 6%) are from urban areas, with a more confirmed epidemiological survey of 59 (42.00%). The average age of the children was 8 months, with a small percentage of children on maternal food (breastfed 25, i.e. 21.37%), with high febrile admission in 99% of children with an average temperature of 38.5oC and an average febrile duration of 4 days, with an average of 7 (+ 2.49) of stools and 5 (+ 2.12) of vomiting. There was a significant difference in hematocrit, leukocyte, electrolyte, glycaemia, and CRP values on admission and discharge. There was predominant isonatremic dehydration, and the compensatory mechanisms followed by the values of the electrolytes ABS, Ph, BE showed a tendency to maintain within the physiological limits. The clinical picture of extraintestinal manifestations included bronchitis, mesenteric lymphadenitis, upper respiratory infections and rash.Rotavirus infection is a serious health and economic problem in our country, so it needs continuous prevention and monitoring in order to reduce the incidence, and thus the need for hospitalization and cure of rotavirus disease.

Association of Systemic Inflammatory Response Syndrome with Bacteremia in Patients with Sepsis.

The aim of this study was to evaluate the usability of systemic inflammatory response syndrome (SIRS) and commonly used biochemical parameters as predictors for positive blood culture in patients with sepsis. The study included 313 patients aged ≥18 years with severe sepsis and septic shock consecutively admitted in the Intensive Care Unit (ICU) of the University Clinic for Infectious Diseases in Skopje, Republic of North Macedonia. The study took place from January 1, 2011 to December 31, 2017. We recorded demographic variables, common laboratory tests, SIRS parameters, site of infection, comorbidities and Sequential Organ Failure Assessment (SOFA) score. Blood cultures were positive in 65 (20.8%) patients with sepsis. Gram-positive bacteria were isolated from 35 (53.8%) patients. From the evaluated variables in this study, only the presence of four SIRS parameters was associated with bacteremia, finding that will help to predict bacteremia and initiate early appropriate therapy in septic patients.

Factors Associated with Lethal Outcome in Patients with Severe Form of Influenza.

INTRODUCTION: Clinical manifestations of influenza range from relatively mild and self-limiting respiratory infections to severe clinical manifestations with significant morbidity and mortality. The awareness of predictive indicators for the lethal outcome of influenza is of particular significance in making timely and exact decision for adequate treatment. The aim of this study was to identify the factors in patients with a severe form of influenza, resulting in lethal outcome. MATERIALS AND METHODS: The investigation was a prospective group comparison conducted at the University Clinic for Infectious Diseases in Skopje, R. Macedonia in the period from January 01, 2012 to January 01, 2015. The study included adult patients with a severe form of influenza who were further categorized into a group of either survived patients or a group of deceased patients. Demographic, clinical and biochemical data were noted in all patients included in the study on admission. The variables of the univariate analysis that showed a significant difference in terms of the outcome were used for creating multivariate logistic and regression analysis of the outcome as dependent factors. The independent predictors for lethal outcome in severe cases of influenza were identified by using logistic regression. RESULTS: The study included 87 patients with a severe form of clinical and laboratory confirmed influenza. The patients were divided in two groups: survived (n = 75) and deceased (n = 75). The overall mortality was 13.79%. Multivariate analysis conducted on admission to hospital identified cardiovascular comorbid diseases (p = 0.014), urea values higher than 8.3 U/L (p = 0.045) and SAPS score (p = 0.048) as independent predictors of the outcome in patients with severe form of influenza. Influenza patients with cardiovascular diseases had 2.024 times greater risk of death from influenza in comparison to the patients having influenza without history of such a disease (OR = 2.024 95% CI 1.842-17.337). Patients with serum urea values higher than 8.3 U/L had 1.89 times higher chance of death compared to patients with normal values (OR = 1.89 95% CI 1.091-11.432). The increase of the SAPS score in one point increased the chance of death in patients with influenza by 1.2% (OR = 1.12 95% CI 1.01-2.976). The ROC analysis indicated that cardiovascular diseases, increased urea values and SAPS score in combination act as a good prognostic model for the fatal outcome. The global authenticity of this predictive model to foresee lethal outcome amounts to 80%, sensitivity being 82%, and specificity 70%. CONCLUSION: Cardiovascular diseases, increased values of urea over 8.3 mmol/l and SAPS score are independent predictive indicators for lethal outcome in severe influenza. Early identification of the outcome predictors in patients with severe influenza will allow implementation of adequate medical treatment and will contribute to decreasing of mortality in patients with severe form of influenza.

Prediction of outcome from community-acquired severe sepsis and septic shock in tertiary-care university hospital in a developing country.

Our aim was to determine the risk factors on mortality in adult patients with community-acquired severe sepsis and septic shock. The main outcome measure was hospital mortality. This prospective single centre study was conducted from January 1, 2008 to December 31, 2010, and included 184 patients, of whom 135 (73.4%) were with severe sepsis and 49 (26.6%) had septic shock. Overall, ninety-five (51.6%) patients have died, 60 (44.4%) in severe sepsis and 35 (71.4%) patients with septic shock. The lung was the most common site of infection 121 (65.8%), and chronic heart failure was the most frequent comorbidity 65 (35.3%). Logistic multivariate analysis identified three independent risk factors for mortality in patients with severe sepsis: positive blood culture (odds ratio, 2.39; 95% confidence interval, 1.13-5.06; P = 0.02), three or more organ dysfunctions (odds ratio, 3.93; 95% confidence interval, 1.62-9.53; P = 0.002), and Simplified Acute Physiology Score (SAPS) II (odds ratio, 1.02; 95% confidence interval, 1.00-1.04; P = 0.01). In addition to SAPS II, positive blood culture, and three or more organ dysfunctions are important independent risk factors for mortality in patients with severe sepsis and septic shock.