ANTIVIRAL RESPONSE OF NATURAL KILLER CELLS IN EARLY STAGE OF COVID-19 PATIENTS

Backgroung: COVID-19 pandemic (SARS-CoV-2) has affected an increasing number of people worldwide, with death rates higher than previous viral epidemics. It is possible that NK cells, known to have great cytokine secreting potential are competent at the onset of the condition and that in some individuals, the viral load is able to exhaust them. Balance between tolerant (CD27- CD11b-), secretory (CD27+ CD11b-/ CD27+ CD11b+) and cytotoxic (CD27- CD11b+) NK cells involved in the inflammatory response and their anti-SARS-CoV-2 activity are still not well established. Strategies that can restore function of NK cells against the virus are worth investigating. Here, we aimed to characterize NK cells frequency, functional subtypes and maturation in early phase of COVID-19 patients, by Multiparametric Flow Cytometry (MFC). Methods: Peripheral blood from 15 COVID-19 patients in early stage of infection (day 1-14, confirmed by RT-PCR), categorized according comorbidities in: G1 (not oncologic;n = 6), G2 (oncologic;n = 3), G3 (hematologic neoplasms;n = 3) and G4 (without comorbidities;n = 3), and 10 healthy samples enrolled the study. Clinical and laboratorial data were collected from electronic medical records. Samples were stained with CD45, CD19, CD3, CD56, CD11b, CD27, acquired on a FACS Canto II (BD Biosciences) and data analyzed with FlowJo V10 software. Results: A lower frequency of lymphocytes was observed in the disease when compared to controls (P < 0.0001) and frequency of NK cells were similar in both groups (P = 0.6605). Although frequency of CD27- CD11b- NK cells was lower in the disease (P = 0.0109), there was a significantly higher frequency of CD27+ CD11b- NK cells in COVID-19 samples when compared to controls (P < 0.0001), featuring a mostly immature profile in the disease. On the other hand, no statistical significance was observed regarding the frequencies of CD27+ CD11b+ (P = 0.1370) and CD27- CD11b+ NK cells with a more mature profile (P = 0.3094). Amongst disease groups, no statistical significance was found regarding frequency of NK cells and G1 showed lower frequency of CD27- CD11b- NK cells (P = 0.0226), while G3 group had an increased frequency of CD27+ CD11b- NK cells (P = 0.0238) when compared to the other groups and controls. Finally, no statistical significance was found in the frequency of CD27+ CD11b+ (P = 0.6691) and CD27- CD11b+ (P = 0.6270) NK cells between disease groups and controls. Conclusion: Although the frequency of NK cells did not show a significant difference between COVID-19 patients and healthy controls, our findings showed a possible change in their maturation profile, which seems to be inversely proportional to normal, with the frequency of CD27+ CD11b- NK cells considerably higher in the disease. This phenotype is directly associated with secretory function of a more immature NK cell and is responsible for triggering inflammatory responses that could lead to severe respiratory failure, what seems to be consistent with COVID-19 profile. A high frequency of cytotoxic cells was observed, which seemed to be similar to what we found in normal heathy samples. Even though unregulated maturation might be associated to a dysfunctional mature NK cell, additional studies of cytotoxicity and activation of NK cells in COVID-19 are required to affirm whether there is functional exhaustion or hyperactivation of the cytotoxic subtypes of these cells.

Non-invasive ventilation in COVID-19 patients, the experience of a level 2 unit

Introduction: COVID-19 has a broad spectrum of severity and, although the majority of those infected are asymptomatic or have mild disease, many need hospitalization and organ support for respiratory failure. The approach to this dysfunction varied across the pandemic, influenced by retrospective data and centre experience. After initial unfavorable data, NIV resumed prominence during the 2nd wave, having been the modality of choice in our intermediate care unit (IU). We describe our NIV cohort and the results of our ventilatory strategy. Methods: Descriptive retrospective study. Data were collected from electronic medical records of 202 COVID-19 patients (PTS) under NIV at the IU between September/20 and March/21. Categorical data are presented as frequency (percentage) and were compared using χ2 -test. Continuous variables were compared using Mann-Whitney U test. Statistical significance was set at p < 0.05. Results: 202 of 469 PTS were submitted to NIV. Mean age was 66 years and 62.8% were male. Most common comorbidities were hypertension, dyslipidemia, obesity and diabetes. Mean admission SOFA score was 3.6. Most PTS underwent corticosteroid therapy, 86.7% in > 1 mg/ kg dosage equivalent. Remdesivir was used in 50%. In 88.6% NIV was the initial modality of ventilatory support, 11.4% after HFNC failure (23). The preferred mode was CPAP with mean maximum pressure of 13 (6-16), titrated to normalization of the work of breathing (WOB). Mean PaO2/FiO2 ratio at start of NIV was 122, < 100 in 43% of PTS. NIV failure occurred in 35.6%, intra-unit mortality was 25.6%. 35 PTS were submitted to invasive mechanical ventilation (IMV), 41% died. Advanced age, intolerance to awake prone and delirium were associated with higher mortality. Conclusions: NIV is a valid option for the management of respiratory failure secondary to COVID-19 ARDS, reducing the need for IMV. Elevated CPAP values, titrated to WOB control, complemented with prolonged periods of awake prone are essential for success.

Impact of remdesivir in COVID-19 patients under non-invasive ventilation in an intermediate care unit

Introduction: COVID-19 has generated enormous difficulties globally due to the high number of critically ill patients and uncertainty of the best therapeutic approach, even after 18 months of pandemic and multiple clinical trials. The antiviral remdesivir (RDV) has shown to reduce time to clinical recovery and, in a subgroup with low flow O2 at time of drug initiation, to reduce mortality by 70% (ACTT-1). Subsequent openlabel RCT, Solidarity and Discovery, didn't confirm these findings. In our unit, a strict protocol was used, including a 5-day cycle of 20 mg dexamethasone and start of HFNC/CPAP when increased work of breathing became noticeable, along with prolonged periods of awake prone position. The use of RDV was a point of significant variability, allowing us to compare outcomes. We describe our unit's experience and RDV impact on patients under non-invasive ventilation (NIV). Methods: Descriptive retrospective study. Data were collected from 202 COVID-19 patients under NIV at our intermediate care unit between September/ 2020 and March/2021, through medical records in the electronic clinical file. Categorical data are presented as frequency (percentage) and were compared using χ2 -test. Continuous variables were compared using Mann-Whitney U test. Statistical significance was set at p < 0.05. Results: Each group consisted of 101 patients, with the group not submitted to RDV being slightly older (mean age 70.5 vs 63 years), more frail (mean CFS 3.5 vs 2.8) and with higher mean SOFA at admission (4.0 vs 3.2). The RDV group had a lower mortality rate (20.8 vs 52.5%;p < 0.001), less NIV failure (20.8 vs 50.5%;p < 0.001), shorter duration of ventilation in survivors (7.0 vs 8.5 days;p = 0.036) and less need for intensive care admission (14.9 vs 23.8%), with favorable impact on mortality (26.6 vs 50%) in this subgroup. Conclusions: In our cohort of patients under NIV, RDV use was associated with lower mortality, less need for IMV and shorter duration of ventilation.

COVID-19 and HIV/AIDS in a cohort study in Sao Paulo, Brazil: outcomes and disparities by race and schooling.

Studies describing characteristics and outcomes of COVID-19 among people living with HIV are currently limited, lacking detailed evaluation of the interplay among demographics, HIV-related variables, and comorbidities on COVID-19 outcomes. This retrospective cohort study describes mortality rates overall and according to demographic characteristics and explores predictors of admission to intensive care unit and death among 255 persons living with HIV with severe acute respiratory syndrome and confirmed SARS-CoV-2 infection in the State of Sao Paulo, Brazil. We found that the overall mortality rate was 4.1/1,000 person-days, with a case-fatality of 34%. Higher rates occurred among older adults, Black/Mixed skin color/race patients, and those with lower schooling. In a multivariable analysis adjusted for age, sex, CD4 count, viral load and number of comorbidities, skin color/race, and schooling remained significantly associated with higher mortality. Although tenofovir use was more frequent among survivors in the univariable analysis, we failed to find a statistically significant association between tenofovir use and survival in the multivariable analysis. Our findings suggest that social vulnerabilities related to both HIV and COVID-19 significantly impact the risk of death, overtaking traditional risk factors such as age, sex, CD4 count, and comorbidities.

Neurologic Manifestations and Complications of SARS-CoV-2 Infection: A Narrative Review

The SARS-CoV-2 pandemic originated in China has caused a severe impact on worldwide health. Respiratory symptoms accompanied by unspecific systemic complaints are the most common presentation. However, neurological symptoms and complications could be found in a patient, and this might confer a poor prognosis. In this view, we aim to present a narrative review of neurological manifestations and complications of SARS-CoV-2 infection by performing literature research. We found nonspecific neurological symptoms such as headache, lethargy, anosmia, and dysgeusia reported in a few cohorts. Case reports of encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain-Barré syndrome have also been published. Finally, cerebrovascular complications resulting from a hypercoagulation state, reported in some cases of SARS-CoV-2 infected patients, confers higher morbidity, especially in younger patients. Future studies should address the implications of the nervous system manifestations and the possibility of virus permanence in nervous tissue. © Wolters Kluwer Health, Inc. All rights reserved.