on behalf of the ImmunoCOVID Brazilian Research Consortium 3Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE 2 , thromboxane B 2 , 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B 4 . Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1b, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.

Objectives: to identify and analyze possibilities for recognizing health needs in the nurses’ work at Family Health Strategy. Methods: a qualitative study with interviews and observation of the nurses’ work in the countryside of São Paulo. The empirical material was subjected to thematic content analysis and interpreted in the light of the health work process. Results: two themes emerged: Possibilities utilized and Possibilities neglected to recognize health needs. Careful observation, welcoming, attention, listening, bonding and dialogue developed by nurses, in live work in action with users, touched on the possibilities, which, taken advantage of, were evidenced in care in spontaneous demand, scheduled consultation, examination gynecological and group activities. Final Considerations: nurses are able to recognize health needs, which can expand their clinical practice and interprofessionality in Family Health.

Objective: to understand the meanings attributed to the social support network of women breastfeeding and in situations of violence by an intimate partner. Method: a qualitative study, carried out with 21 women, through semi-structured interviews and data analyzed by the Method of Interpretation of the Senses in the light of the conceptual framework of Social Support Network. Results: all women suffered violence by the partner in the puerperium and only one of them maintained exclusive breastfeeding until 180 days postpartum. In the analysis, the category entitled “The action of the social support network in the face of breastfeeding in the context of intimate partner violence” emerged, with two subcategories: “Interpersonal support network” and “Institutional support network”. In the interpersonal network, the partner was little mentioned, on the other hand, there was a greater participation of other women. In the institutional network, non-resolution and actions centered on biological character were evident. Conclusions: the search for help in the interpersonal network stood out in comparison to the institutional network, both with regard to the issue of violence and breastfeeding and the actions related to it, mostly ineffective, characterized by counseling and referrals.

Objective: To identify the steps of the Nursing Process and integral care. Method: Document analysis study on medical and nursing consultations records during postpartum conducted in primary health units in inland São Paulo state. The analysis comprised the registered steps, the sequence of steps, and the approach of psychosocial questions. The data are presented by frequency, percentage, and the expressed content of care. Results: The analyzed records amounted to 341. Out of these, 100% presented History; 62.2%, Nursing Diagnosis; 5.3%, Planning; 99.1%, Implementation; and 50.1%, Evaluation. Regarding the sequence of steps, 47.5% of the medical records presented three steps. In the incorporation of the principle of integrality, a more frequent presence of the biological approach was observed. Conclusion: This study shows the change of practice of nurses, with efforts to register the Nursing Process, and that the integrality of care constitutes a challenge to surpass a model of care which is fragmented and decontextualized from the life conditions of people.

Objective: to map the recommendations of the coping strategies for violence against children, adolescents and women in the context of social isolation due to Covid-19. Method: a scoping review according to the Joanna Briggs Institute, through a research strategy carried out in the gray literature by the CAPES Portal and in the following databases: SCIELO, LILACS, PubMed, CINAHL, Web of Science, and Institutional Repository for Information Exchange of the Pan American Health Organization. The analysis of the identified material was carried out by three independent reviewers. The extracted data were analyzed and synthesized in narrative form. Results: of the 526 studies found, 59 were kept for review and their content was summarized in six categories: 1) prevention; 2) identification and intervention; 3) continued care; 4) care for the safety and mental health of the professionals; 5) intersectoriality/interdisciplinarity; and 6) special care for vulnerable populations. Conclusion: the services must guarantee continuous, intersectoral and safe care, especially in the context of mental health, as well as community awareness must be promoted. Health professionals must be sensitive and alert to signs of violence, intervening immediately and connected to the safety network.

Cytokine storms and hyperinflammation, potentially controlled by glucocorticoids, occur in COVID-19; the roles of lipid mediators and acetylcholine (ACh) and how glucocorticoid therapy affects their release in Covid-19 remain unclear. Blood and bronchoalveolar lavage (BAL) samples from SARS-CoV-2- and non-SARS-CoV-2-infected subjects were collected for metabolomic/lipidomic, cytokines, soluble CD14 (sCD14), and ACh, and CD14 and CD36-expressing monocyte/macrophage subpopulation analyses. Transcriptome reanalysis of pulmonary biopsies was performed by assessing coexpression, differential expression, and biological networks. Correlations of lipid mediators, sCD14, and ACh with glucocorticoid treatment were evaluated. This study enrolled 190 participants with Covid-19 at different disease stages, 13 hospitalized non-Covid-19 patients, and 39 healthy-participants. SARS-CoV-2 infection increased blood levels of arachidonic acid (AA), 5-HETE, 11-HETE, sCD14, and ACh but decreased monocyte CD14 and CD36 expression. 5-HETE, 11-HETE, cytokines, ACh, and neutrophils were higher in BAL than in circulation (fold-change for 5-HETE 389.0; 11-HETE 13.6; ACh 18.7, neutrophil 177.5, respectively). Only AA was higher in circulation than in BAL samples (fold-change 7.7). Results were considered significant at P<0.05, 95%CI. Transcriptome data revealed a unique gene expression profile associated with AA, 5-HETE, 11-HETE, ACh, and their receptors in Covid-19. Glucocorticoid treatment in severe/critical cases lowered ACh without impacting disease outcome. We first report that pulmonary inflammation and the worst outcomes in Covid-19 are associated with high levels of ACh and lipid mediators. Glucocorticoid therapy only reduced ACh, and we suggest that treatment may be started early, in combination with AA metabolism inhibitors, to better benefit severe/critical patients.