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The Coronavirus Disease 2019 (COVID-19) pandemic posed various challenges to the healthcare system and disease management. This study aimed to describe changes in the clinical characteristics and outcomes of hospitalized patients during the first year of the COVID-19 pandemic in a city in southern Brazil. This prospective study was carried out in two tertiary care private hospitals in Curitiba. A total of 1151 patients hospitalized between March 2020 and March 2021 were included. We identified three epidemiological critical periods of the pandemic and compared patients’ characteristics and the frequencies of oral intubation, intensive care unit (ICU) admission and mortality. Continuous variables were analyzed by variance analysis model (ANOVA) or the Kruskal–Wallis nonparametric test and categorical variables by the chi-square or Fisher’s exact test. Models for univariate and multivariate logistic regression analysis were adjusted to identify the factors associated with mortality. All p-values were two-tailed and p<0.05 was considered statistically significant. The average age of the patients was 58 years and 60.9% (n = 701) were males. The most prevalent comorbidities were systemic arterial hypertension, diabetes and obesity. There were no significant variations in the demographic characteristics and previous comorbidities of the patients for the different periods of analysis. Mortality was positively associated with the age ≥65 years and the presence of one or more cardiometabolic comorbidities (p<0.001). March 2021 was the most important critical period of the pandemic since there were higher frequencies of patients admitted later in the course of the disease, with desaturation and more symptoms at hospital admission (p<0.001). There was also an increase in the duration of hospital stay (p<0.001) and the frequencies of all critical outcomes for this period: oral intubation (p<0.001), ICU admission (p = 0.606) and mortality (p = 0.001). Our key findings revealed that, although there were no statistically significant differences between the subgroups of hospitalized patients over time in terms of demographic characteristics and comorbidities, the course of COVID-19 was significantly more severe for patients admitted to the hospital at the end of the first year of the pandemic in Brazil.

With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1] The study evaluated [LG2] the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

Background This study aimed to determine the association between glycemic variability (GV) and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods We prospectively analyzed data from inpatients (> 18 years old) with RT-PCR confirmed COVID-19 admitted between March 2020 and July 2021. All patients were hospitalized for more than 48 h and had at least six point-of-care capillary glucose tests obtained three times daily in the pre-prandial period during hospitalization. GV was measured using the glucose standard deviation (SD) and coefficient of variation (CV). ROC curve was adjusted to determine the SD and CV cutoff values associated with mortality (44.7 mg/dL and 27.5%, respectively); values above these were considered indicative of high GV. Logistic regression models were fitted to explore the association between GV and mortality in patients with and without diabetes. Results A total of 628 patients were stratified into SD < 44.7 mg/dL (n = 357) versus ≥ 44.7 mg/dL (n = 271) and CV < 27.5% (n = 318) versus ≥ 27.5% (n = 310) groups. After controlling for age, sex, presence of diabetes mellitus (DM) and cardiovascular disease, we found a significant association between high GV and mortality (odds ratio 2.99 [1.88–4.77] for SD and 2.43 [1.54–3.85] for CV; p values < 0.001). The mortality rate was higher with SD ≥ 44.7 mg/dL and CV ≥ 27.5% compared to that with SD < 44.7 mg/dL and CV < 27.5%, regardless of DM (p < 0.001 for all). Conclusion High glycemic variability was independently associated with mortality in patients with and without DM, who were hospitalized with COVID-19.

COVID-19 is a viral disease associated with an intense inflammatory response. Macrophage Activation Syndrome (MAS), the complication present in secondary hemophagocytic lymphohistiocytosis (sHLH), shares many clinical aspects observed in COVID-19 patients, and investigating the cytolytic function of the responsible cells for the first line of the immune response is important. Formalin-fixed paraffin-embedded lung tissue samples obtained by post mortem necropsy were accessed for three groups (COVID-19, H1N1, and CONTROL). Polymorphisms in MAS cytolytic pathway (PRF1; STX11; STXBP2; UNC13D and GZMB) were selected and genotyping by TaqMan® assays (Thermo Fisher Scientific, MA, USA) using Real-Time PCR (Applied Biosystems, MA USA). Moreover, immunohistochemistry staining was performed with a monoclonal antibody against perforin, CD8+ and CD57+ proteins. Histopathological analysis showed high perforin tissue expression in the COVID-19 group; CD8+ was high in the H1N1 group and CD57+ in the CONTROL group. An association could be observed in two genes related to the cytolytic pathway (PRF1 rs885822 G/A and STXBP2 rs2303115 G/A). Furthermore, PRF1 rs350947132 was associated with increased immune tissue expression for perforin in the COVID-19 group. The genotype approach could help identify patients that are more susceptible, and for this reason, our results showed that perforin and SNPs in the PRF1 gene can be involved in this critical pathway in the context of COVID-19.

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.

The COVID-19 pandemic, promoted by the SARS-CoV-2 respiratory virus, has resulted in widespread global morbidity and mortality. The immune response against this pathogen has shown a thin line between protective effects and pathological reactions resulting from the massive release of cytokines and poor viral clearance. The latter is possibly caused by exhaustion, senescence, or both of TCD8+ cells and reduced activity of natural killer (NK) cells. The imbalance between innate and adaptive responses during the early stages of infection caused by SARS-CoV-2 contributes to the ineffective control of viral spread. The present study evaluated the tissue immunoexpression of the tissue biomarkers (Arginase-1, CCR4, CD3, CD4, CD8, CD20, CD57, CD68, CD138, IL-4, INF-α, INF-γ, iNOS, PD-1, Perforin and Sphingosine-1) to understand the cellular immune response triggered in patients who died of COVID-19. We evaluated twenty-four paraffin-embedded lung tissue samples from patients who died of COVID-19 (COVID-19 group) and compared them with ten lung tissue samples from patients who died of H1N1pdm09 (H1N1 group) with the immunohistochemical markers mentioned above. In addition, polymorphisms in the Perforin gene were genotyped through Real-Time PCR. Significantly increased tissue immunoexpression of Arginase, CD4, CD68, CD138, Perforin, Sphingosine-1, and IL-4 markers were observed in the COVID-19 group. A significantly lower immunoexpression of CD8 and CD57 was also found in this group. It is suggested that patients who died from COVID-19 had a poor cellular response concerning viral clearance and adaptive response going through tissue repair.