Factors associated with functional decline in COVID-19 elderly survivors hospitalized in a tertiary care center.

BACKGROUND: The information on functional decline after hospitalization for COVID-19 is limited in older adults (OAs). OBJECTIVE: To determine the association of inflammation (ferritin) and coagulation markers (D-dimer) and clinical factors with the functional status of OAs who suffered from COVID-19 six months after hospital discharge in Mexico. MATERIAL AND METHODS: Ambispective cohort study of 158 patients older than 65 years hospitalized for moderate-severe COVID-19 with complete electronic records that would allow to collect information and to contact them six months after discharge. Functional impairment was defined as a decrease ≥ 10 points on the Barthel index. Using logistic regression analysis, the risk of association of biochemical and clinical factors with functional deterioration during follow-up was determined. RESULTS: 46.2% of participants exhibited functional decline. Associated factors included age ≥ 73 years (OR = 2.53), chronic kidney disease (OR = 4.57), an ABC-Goals score ≥ 8 (OR = 2.4), ferritin ≥ 605 ng/mL (OR = 3.94) and D-dimer ≥ 930 ng/mL (OR = 17.56). CONCLUSION: COVID-19 infection did not only represent a disease with a high risk of mortality during the acute phase, but is also associated with a high risk of functional impairment after hospital discharge.

ANTECEDENTES: La información acerca del deterioro funcional después de una hospitalización por COVID-19 es limitada en personas mayores (PM). OBJETIVO: Determinar la asociación entre marcadores de inflamación (ferritina), coagulación (dímero D), factores clínicos y el estado funcional de PM que padecieron COVID-19 a seis meses del alta hospitalaria en México. MATERIAL Y MÉTODOS: Estudio de cohorte ambispectiva de 158 pacientes mayores de 65 años hospitalizados por COVID-19 moderado-grave con expediente electrónico completo que permitiera recolectar información y contactarlos a los seis meses del alta. Se definió deterioro funcional como disminución ≥ 10 puntos del índice de Barthel. Mediante regresión logística se determinó el riesgo de asociación entre factores bioquímicos y clínicos y deterioro funcional en el tiempo de seguimiento. RESULTADOS: 46.2 % de los participantes presentó pérdida funcional. Los factores asociados fueron edad ≥ 73 años (RM = 2.53), enfermedad renal crónica (RM = 4.57), puntuación ABC-Goals ≥ 8 (RM = 2.4), ferritina ≥ 605 ng/mL (RM = 3.94) y dímero-D ≥ 930 ng/mL FEU (RM = 17.56). CONCLUSIÓN: La infección por COVID-19 no solo representa una enfermedad con alto riesgo de mortalidad durante la fase aguda, sino que también se asocia a un alto riesgo de deterioro funcional posterior al egreso hospitalario.

Puntaje APP como predictor de mortalidad en pacientes con síndrome de dificultad respiratoria agudo grave por COVID-19 en un hospital referencial del norte del Perú / APP score as a predictor of mortality in patients with severe acute respiratory distress syndrome due to COVID-19 in a reference hospital in northern of Peru

INTRODUCCIÓN: La mortalidad por pacientes por COVID-19 grave que desarrollaban neumonía grave y síndrome de dificultad respiratoria agudo (SDRA) grave ha sido significativa a pesar del tratamiento oportuno. Es importante determinar predictores tempranos de enfermedad que nos ayuden a estratificar aquellos pacientes con mayor riesgo de fallecer. Se pretende estudiar el comportamiento del puntaje APP (APPS) como predictor de ello, basados en algunos reportes de uso y utilidad en el SDRA. no COVID-19. OBJETIVO: Determinar si el APPS es útil como predictor de mortalidad en SDRA. por COVID-19 grave. PACIENTES Y MÉTODO: Se realizó un estudio tipo cohorte retrospectivo, incluyendo pacientes de la Unidad de Cuidados Intensivos (UCI), con SDRA. por COVID-19 grave, que ingresaron a la UCI del Hospital Regional Docente de Trujillo (HRDT) en el período abril 2020- abril 2021. Se evalúo la utilidad del APPS como predictor de mortalidad em dicha población. RESULTADOS: El APPS demostró ser un factor asociado a mortalidad en pacientes con SDRA. y COVID-19 grave (RPa 1,34; IC 95% 1,16 a 1,56; p < 0,001). Además, encontramos que, al realizar un modelo de predicción ajustado por edad, sexo, SOFA, APPS, shock, Indice de Charlson (ICh), se comportan como factores asociados a mortalidad el APPS, el sexo masculino (RPa: 1,48; IC 95% 1,09 a 2,049; p < 0,05) y el ICh (RPa: 1,11; IC 95% 1,02 a 1,21; p < 0,05). CONCLUSIÓN: El APPS, el sexo masculino y el ICh son predictores de mortalidad en SDRA. por COVID-19 grave.

BACKGROUND: Mortality in patients with severe COVID-19 who developed severe pneumonia and severe Acute Respiratory Distress Syndrome (ARDS) has been significant despite timely treatment. It is important to determine early predictors of disease that help us to stratify those patients with a higher risk of death. It is intended to study the behavior of the APPS score as a predictor of this, based on some reports of use and usefulness in non-COVID-19 ARDS. AIM: To determine if the APP score is useful as a predictor of mortality in ARDS due to severe COVID-19. METHOD: A retrospective cohort study was carried out, including patients from the Intensive Care Unit (ICU) with ARDS due to severe COVID-19 who were admitted to the ICU of the Trujillo Regional Teaching Hospital (HRDT) in the period March 2020 to March 2021. The usefulness of the APP score as a predictor of mortality in mentioned population was evaluated. RESULTS: The APP score proved to be a factor associated with mortality in patients with ARDS and severe COVID-19 (APR 1.34; 95% CI 1.16 to 1.56; p < 0.001). We also found that when performing a prediction model adjusted for age, sex, SOFA, APP score, shock and Charlson Index (ICh) we found that the APP score, male sex (APR: 1.48; 95% CI 1.09 to 2.049; p < 0.05) and the ICh behave as factors associated with mortality (RPa: 1.11; 95% CI 1.02 to 1.21; p < 0.05). CONCLUSION: The APP score, male sex, and ICh are predictors of mortality in ARDS due to severe COVID-19.

Receiver operating characteristic (ROC) to determine cut-off points of clinical and biomolecular markers to discriminate mortality in severe COVID-19 living at high altitude.

BACKGROUND: In 2020, Ecuador had one of the highest death rates because of COVID-19. The role of clinical and biomolecular markers in COVID disease prognosis, is still not well supported by available data. In order for these markers to have practical application in clinical decision-making regarding patient treatment and prognosis, it is necessary to know an optimal cut-off point, taking into consideration ethnic differences and geographic conditions. AIM: To determine the value of clinical and biomolecular markers, to predict mortality of patients with severe COVID-19 living at high altitude. METHODS: In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of ROC, sensitivity, specificity and likelihood ratios were calculated to determine levels of clinical and biomolecular markers that best differentiate survivors versus non-survivors in severe COVID subjects that live at a high altitude setting. RESULTS: Selected cut-off values for ferritin (≥ 1225 ng/dl, p = 0.026), IL-6 (≥ 11 pg/ml, p = 0.005) and NLR (≥ 22, p = 0.008) at 24 h, as well as PaFiO2 (≤ 164 mmHg, p = 0.015), NLR (≥ 16, p = p = 0.013) and SOFA (≥ 6, p = 0.031) at 72 h, appear to have good discriminating power to differentiate survivors versus non-survivors. Additionally, odds ratios for ferritin (OR = 3.38); IL-6 (OR = 17.07); PaFiO2 (OR = 4.61); NLR 24 h (OR = 4.95); NLR 72 h (OR = 4.46), and SOFA (OR = 3.77) indicate increased risk of mortality when cut-off points were taken into consideration. CONCLUSIONS: We proposed a straightforward and understandable method to identify dichotomized levels of clinical and biomolecular markers that can discriminate between survivors and non-survivors patients with severe COVID-19 living at high altitudes.

Mortality in patients with interstitial lung diseases hospitalized by severe or critical COVID-19.

BACKGROUND: Since the first case of severe COVID-19, its effect on patients with previous interstitial lung disease (ILD) has been uncertain. We aimed to describe baseline clinical characteristics in ILD patients hospitalized by critical COVID and compare mortality during hospitalization. METHODS: We studied patients with ILD with COVID-19 and a control group matched by age, 1:2 ratio with COVID-19 without previous lung disease. On admission, laboratory tests and sociodemographic variables were evaluated. We evaluated patients critically ill and compared baseline characteristics and mortality in each group. Additionally, we performed a sub-analysis of ILD patients who died versus survivors. RESULTS: Forty-one patients and 82 controls were analyzed. In the group of ILD with COVID-19 there was a predominance of women (65 versus 33%: p < 0.001); lower leukocytes (9 ± 6 versus 11 ± 7, p = 0.01) and neutrophils (8 ± 5 versus 10 ± 6, p = 0.02). The most common ILD was secondary to autoimmune diseases. Patients with ILD and critical COVID-19 showed a significantly higher mortality compared with those without previous ILD (63 versus 33%, p = 0.007). Patients who died in this group had higher BMI (28 ± 6 versus 25 ± 4 kg/m2, p = 0.05), less extended hospital stay (20 ± 17 versus 36 ± 27 days, p = 0.01), and fewer days of evolution (9 ± 7 versus 16 ± 16, p = 0.05). CONCLUSIONS: We found higher mortality in patients with ILD with critical COVID-19. Higher BMI and comorbidities were present in the non-survivors.

Factores asociados al deterioro funcional en adultos mayores sobrevivientes de COVID-19 hospitalizados en un centro de tercer nivel / Factors associated with functional decline in COVID-19 elderly survivors hospitalized in a tertiary care center

Resumen Antecedentes: La información acerca del deterioro funcional después de una hospitalización por COVID-19 es limitada en personas mayores (PM). Objetivo: Determinar la asociación entre marcadores de inflamación (ferritina), coagulación (dímero D), factores clínicos y el estado funcional de PM que padecieron COVID-19 a seis meses del alta hospitalaria en México. Material y métodos: Estudio de cohorte ambispectiva de 158 pacientes mayores de 65 años hospitalizados por COVID-19 moderado-grave con expediente electrónico completo que permitiera recolectar información y contactarlos a los seis meses del alta. Se definió deterioro funcional como disminución ≥ 10 puntos del índice de Barthel. Mediante regresión logística se determinó el riesgo de asociación entre factores bioquímicos y clínicos y deterioro funcional en el tiempo de seguimiento. Resultados: 46.2 % de los participantes presentó pérdida funcional. Los factores asociados fueron edad ≥ 73 años (RM = 2.53), enfermedad renal crónica (RM = 4.57), puntuación ABC-Goals ≥ 8 (RM = 2.4), ferritina ≥ 605 ng/mL (RM = 3.94) y dímero-D ≥ 930 ng/mL FEU (RM = 17.56). Conclusión: La infección por COVID-19 no solo representa una enfermedad con alto riesgo de mortalidad durante la fase aguda, sino que también se asocia a un alto riesgo de deterioro funcional posterior al egreso hospitalario.

Abstract Background: The information on functional decline after hospitalization for COVID-19 is limited in older adults (OAs). Objective: To determine the association of inflammation (ferritin) and coagulation markers (D-dimer) and clinical factors with the functional status of OAs who suffered from COVID-19 six months after hospital discharge in Mexico. Material and methods: Ambispective cohort study of 158 patients older than 65 years hospitalized for moderate-severe COVID-19 with complete electronic records that would allow to collect information and to contact them six months after discharge. Functional impairment was defined as a decrease ≥ 10 points on the Barthel index. Using logistic regression analysis, the risk of association of biochemical and clinical factors with functional deterioration during follow-up was determined. Results: 46.2 % of participants exhibited functional decline. Associated factors included age ≥ 73 years (OR = 2.53), chronic kidney disease (OR = 4.57), an ABC-Goals score ≥ 8 (OR = 2.4), ferritin ≥ 605 ng/mL (OR = 3.94) and D-dimer ≥ 930 ng/mL (OR = 17.56). Conclusion: COVID-19 infection did not only represent a disease with a high risk of mortality during the acute phase, but is also associated with a high risk of functional impairment after hospital discharge.

Aeroallergen immunotherapy associated with reduced risk of severe COVID-19 in 1095 allergic patients.

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

Post-COVID-19 syndrome and quality of life impairment in severe COVID-19 Mexican patients.

Introduction: Post-COVID-19 syndrome (PCS) usually occurs 3 months after the onset of COVID-19 with a symptom duration of at least 2 months without an alternative diagnosis. Objective: This study aimed to describe the prevalence, characteristics, and impact on the quality of life (QoL) of post-COVID-19 syndrome in patients with a history of hospitalization for COVID-19. Materials and methods: We conducted a cross-sectional study. Patients who required hospitalization due to COVID-19 between March 2020 and October 2021 were invited to answer a PCS questionnaire and the EQ-5D instrument. A total of 246 patients were included: 187 (76%) met the definition of PCS and 54% were men, with a median age of 50 years (IQR 41-63). Results: From 187 patients with PCS, the median time to symptom onset after hospital discharge was 1 day (IQR 1-20), and the median symptom duration was 150 days (IQR 90-225). A total of 27 different symptoms were reported; the most frequent were difficulty concentrating (81%), dyspnea (75%), arthralgia (71%), fatigue (68%), and hair loss (60%). Some symptoms, such as difficulty concentrating, arthralgia/myalgia, and hair loss, were more prevalent in women with PCS. Patients with PCS had a higher frequency of tobacco smoking (37 vs. 4%, p = 0.02) and increased severity of lung involvement in the initial chest tomography (75 vs. 58%, p = 0.01) than those without PCS. Patients with PCS were less likely to receive antivirals (15.5 vs. 27%, p = 0.04). No difference between ICU admission, mechanical ventilation, and length of hospital stay was found. Patients with PCS had a lower visual analog scale result for EQ-5D vs. those without (80 [IQR 70-90] vs. 89.5 [IQR 75-90], p = 0.05). All five QoL dimensions were affected in PCS patients, showing increased pain/discomfort (67 vs. 39%, p = < 0.001), difficulties in performing usual activities (39.2 vs. 20.3%, p = 0.03), and anxiety/depression (57.5 vs. 37%, p = 0.02). Conclusion: PCS occurred in 76% of hospitalized patients with prolonged duration and QoL impairment. Neurological symptoms such as difficulty concentrating were the most frequent symptoms. Timely diagnostic and therapeutic interventions are required.

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.

Leukocyte surface expression of the endoplasmic reticulum chaperone GRP78 is increased in severe COVID-19.

Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum-resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.

Asociación de marcadores inflamatorios en COVID-19 severo al ingreso con mortalidad y disfunción orgánica / Association of severe COVID-19 inflammatory markers at hospitalization with mortality and organic dysfunction / Associação de marcadores inflamatórios em COVID-19 grave na admissão com mortalidade e disfunção orgânica

Resumen: Introducción: se ha demostrado que los niveles iniciales de marcadores inflamatorios involucrados en COVID-19 (ej. ferritina, proteína C reactiva, procalcitonina, dímero D e interleucina-6) se relacionan con la mortalidad, sin encontrar resultados similares en pacientes con COVID-19 severo o quienes se encuentran bajo ventilación mecánica invasiva. Objetivo: determinar el nivel sérico con mayor sensibilidad y especificidad en los marcadores inflamatorios con relación a la mortalidad y gravedad de la disfunción orgánica en pacientes con COVID-19 severo usuarios de ventilación mecánica invasiva en las primeras 48 horas tras el ingreso hospitalario. Material y métodos: se realizó un estudio descriptivo de tipo cohorte retrospectiva y longitudinal en pacientes con diagnóstico de COVID-19 severo que fueran intubados antes de 48 horas tras el ingreso hospitalario por falla respiratoria aguda de enero de 2021 a agosto de 2021. Se determinó la relación entre los niveles de estos marcadores con las escalas pronósticas (SOFA, APACHE-II y SAPS-II), días de estancia hospitalaria, días en la Unidad de Terapia Intensiva Respiratoria, días de ventilación mecánica invasiva y las características de la mecánica ventilatoria inicial. Se agruparon los marcadores en niveles elevados y bajos para determinar su papel individual y en conjunto con los desenlaces. Resultados: se estudió una N = 218, con predominio de género masculino (77.5%) con media de edad de 60.3 ± 12.8 años. La hipertensión arterial sistémica y la diabetes mellitus tipo 2 fueron las comorbilidades más prevalentes (50.5% y 26.1%, respectivamente). La mediana de la relación PaO2/FiO2 fue de 128 mmHg (83.3-204.2), con una mortalidad total de 24.8%. Los niveles de biomarcadores con mayor sensibilidad para mortalidad y disfunción orgánica fueron: proteína C reactiva: ≥ 16 mg/dL, procalcitonina: ≥ 0.83 ng/mL, dímero D: ≥ 1,290 ng/mL, ferritina: ≥ 1,450 ng/mL e interleucina-6: ≥ 195 pg/mL. La procalcitonina y la interleucina-6 de manera aislada demostraron mayor riesgo de mortalidad y peor disfunción orgánica. Los marcadores inflamatorios se relacionaron a peor desenlace con respecto a las características del sistema respiratorio y el grado de alteración en gases arteriales. De forma conjunta (≥ 3 altos), los marcadores inflamatorios se relacionaron a mayor número de días de estancia hospitalaria, días en la Unidad de Terapia Intensiva Respiratoria y de días de ventilación mecánica invasiva. La proteína C reactiva, procalcitonina e interleucina-6 se asociaron a mayor riesgo de peor grado de disfunción orgánica por SOFA y peor pronóstico por APACHE-II y SAPS-II. Conclusión: la medición individual y conjunta de marcadores inflamatorios al ingreso hospitalario puede identificar a pacientes con mayor riesgo de estancia hospitalaria prolongada, así como ventilación mecánica invasiva, con mayor riesgo de mortalidad en el caso de procalcitonina e interleucina-6.

Abstract: Introduction: it has being demonstrated that the initial levels of inflammatory markers involved in COVID-19 (eg. C-reactive protein, procalcitonin, D-dimer, ferritin and interleukine-6) have an association with mortality, in different degree on severe COVID-19 patients or in those on invasive mechanical ventilation secondary to COVID-19 related acute respiratory distress syndrome. Objective: to determine the serum levels of these markers with the greatest sensibility and specificity for mortality and worst organ dysfunction in patients under invasive mechanical ventilation within the first 48 hours of hospitalization. Material and methods: in a retrospective and longitudinal cohort of severe COVID-19 patients on invasive mechanical ventilation within first 48 hours of hospitalization due to respiratory failure through January 2021 to August 2021, we determined the relation of inflammatory markers with prognostic scores (SOFA, APACHE-II and SAPS-II), hospital length-of-stay (LOS), intensive care LOS, invasive ventilation's days and initial ventilatory mechanics. We divided markers in high and low levels to identify the relation between each one and by groups with the outcomes. Results: we studied a N = 218, with male predominance (77.5%) and mean age of 60.3 ± 12.8 years. Arterial hypertension and diabetes mellitus type 2 were the most prevalent co-comorbidities (50.5% y 26.1%, respectively). The median initial PaO2/FiO2 was 128 mmHg (83.3-204.2), with a total mortality rate of 24.8%. Inflammatory markers levels with the highest sensibility for mortality were: C-reactive protein: ≥ 16 mg/dL, procalcitonin: ≥ 0.83 ng/mL, D-dimer: ≥ 1,290 ng/mL, ferritin: ≥ 1,450 ng/mL and interleukin-6: ≥ 195 pg/mL. Procalcitonin and interleukin-6 were associated to higher risk of mortality and worst organ dysfunction. The inflammatory markers were related with worst outcome in relation to respiratory mechanics and the amount of arterial-blood gases' alteration. Having ≥ 3 inflammatory markers within high levels was associated with prolonged LOS, more intensive care LOS and more days under invasive mechanical ventilation. The c-reactive protein, procalcitonin and interleukin-6 had higher organic dysfunction defined by SOFA and worst outcome defined by APACHE-II and SAPS-II. Conclusion: individual and joint measurement of inflammatory markers at hospitalization can identify patients with greater risk of longer hospital LOS, intensive care LOS and longer mechanical ventilation's days, with greater risk of mortality with higher procalcitonin and interleukine-6 serum levels.

Resumo: Introdução: demonstrou-se que os níveis iniciais de marcadores inflamatórios envolvidos no COVID-19 (por exemplo, ferritina, proteína C reativa, procalcitonina, D-dímero e interleucina-6) estão relacionados à mortalidade, sem encontrar resultados semelhantes em pacientes com COVID-19 grave ou que estejam sob ventilação mecânica invasiva. Objetivos: nosso objetivo foi determinar o nível sérico com maior sensibilidade e especificidade em marcadores inflamatórios em relação à mortalidade e gravidade da disfunção orgânica em pacientes com COVID-19 grave que usaram ventilação mecânica invasiva nas primeiras 48 horas após a admissão hospitalar. Material e métodos: realizou-se um estudo descritivo do tipo coorte retrospectivo e longitudinal em pacientes diagnosticados com COVID-19 grave que foram intubados nas primeiras 48 horas após a internação hospitalar por insuficiência respiratória aguda no período de janeiro de 2021 a agosto de 2021. A relação entre os níveis desses marcadores com as escalas de prognóstico (SOFA, APACHE-II e SAPS-II), dias de internação, dias na unidade de terapia intensiva respiratória, dias de ventilação mecânica invasiva e as características da ventilação mecânica inicial. Agrupou-se marcadores em níveis altos e baixos para determinar seu papel individualmente e em conjunto com os resultados. Resultados: estudou-se uma N = 218, com predominância do sexo masculino (77.5%) com idade média de 60.3 ± 12.8 anos. A hipertensão arterial sistêmica e a diabetes mellitus tipo 2 foram as comorbidades mais prevalentes (50.5% e 26.1%, respectivamente). A mediana da relação PaO2/FiO2 foi de 128 mmHg (83.3-204.2), com mortalidade total de 24.8%. Os níveis de biomarcadores com maior sensibilidade para mortalidade e disfunção orgânica foram: proteína C reativa: ≥ 16 mg/dL, procalcitonina: ≥ 0.83 ng/mL, dímero: ≥ 1.290 ng/mL, ferritina: ≥ 1.450 ng/mL, e interleucina-6: ≥ 195 pg/mL. A procalcitonina e a interleucina-6 sozinhas demonstraram maior risco de mortalidade e pior disfunção orgânica. Os marcadores inflamatórios foram relacionados a pior evolução quanto às características do sistema respiratório e ao grau de alteração dos gases arteriais. Juntos (≥ 3 altos), os marcadores inflamatórios foram relacionados a um maior número de dias de internação, dias na unidade de terapia intensiva respiratória e dias de ventilação mecânica invasiva. A proteína C-reativa, procalcitonina e interleucina-6 foram associadas a maior risco de pior grau de disfunção orgânica pelo SOFA e pior prognóstico pelo APACHE-II e SAPS-II. Conclusão: a medida individual e conjunta de marcadores inflamatórios na admissão hospitalar pode identificar pacientes com maior risco de internação prolongada e ventilação mecânica invasiva, com maior risco de mortalidade no caso da procalcitonina e interleucina-6.

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

In-hospital severe COVID-19 in a philanthropic tertiary hospital setting: is asthma a concern? A retrospective study

ABSTRACT BACKGROUND: The frequency of coronavirus disease 2019 (COVID-19) cases among asthmatics has been reported to be reduced. However, the findings regarding the association between asthma and the risk of severe COVID-19 have been divergent. OBJECTIVE: To investigate whether asthma is associated with a reduced risk of development of severe COVID-19. DESIGN AND SETTING: Retrospective analysis on COVID-19 surveillance databases at two tertiary-level hospitals in São Paulo, Brazil. METHODS: The medical records of patients hospitalized due to COVID-19 between March and August 2020 were reviewed in accordance with the clinical, laboratorial, radiological and epidemiological criteria for COVID-19, and for comorbidities. RESULTS: Among the adult patients included (> 18 years of age) there were 52 asthmatics and 1,318 non-asthmatics. Their median ages and interquartile ranges (IQR) were, respectively, 54 (41-69) and 60 (44-72) years. At least one comorbidity was seen in 73% of asthmatics and 56% of the non-asthmatics. Among the asthmatics, most presented mild asthma (92%) and the prevalence of chronic obstructive pulmonary disease (COPD) was high (27%). The asthmatics presented an unadjusted odds ratio (OR) for severe COVID-19 of 0.89 (95% confidence interval, CI 0.5-1.56); and OR 0.88 (95% CI 0.5 -1.68) after multivariable adjustment. Age > 60 years, male sex, hypertension, diabetes, cancer and homelessness were covariates associated with increased odds for severe COVID-19. Kaplan-Meier estimated survival over hospitalization of up to 30 days did not differ between the groups (log-rank P = 0.09). CONCLUSIONS: The association between asthma and decreased risk of severe COVID-19 or increased survival was statistically non-significant.

Correlating drug prescriptions with prognosis in severe COVID-19: first step towards resource management.

BACKGROUND: Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis. METHODS: The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient. RESULTS: We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups. CONCLUSIONS: In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.

IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19.

Interferons (IFNs) are a group of cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities. Type I IFNs amplify and propagate the antiviral response by interacting with their receptors, IFNAR1 and IFNAR2. In COVID-19, the IFNAR2 (interferon alpha and beta receptor subunit 2) gene has been associated with the severity of the disease, but the soluble receptor (sIFNAR2) levels have not been investigated. We aimed to evaluate the association of IFNAR2 variants (rs2236757, rs1051393, rs3153, rs2834158, and rs2229207) with COVID-19 mortality and to assess if there was a relation between the genetic variants and/or the clinical outcome, with the levels of sIFNAR2 in plasma samples from hospitalized individuals with severe COVID-19. We included 1,202 subjects with severe COVID-19. The genetic variants were determined by employing Taqman® assays. The levels of sIFNAR2 were determined with ELISA in plasma samples from a subgroup of 351 individuals. The rs2236757, rs3153, rs1051393, and rs2834158 variants were associated with mortality risk among patients with severe COVID-19. Higher levels of sIFNAR2 were observed in survivors of COVID-19 compared to the group of non-survivors, which was not related to the studied IFNAR2 genetic variants. IFNAR2, both gene, and soluble protein, are relevant in the clinical outcome of patients hospitalized with severe COVID-19.

Physiological Network Is Disrupted in Severe COVID-19.

The human body is a complex system maintained in homeostasis thanks to the interactions between multiple physiological regulation systems. When faced with physical or biological perturbations, this system must react by keeping a balance between adaptability and robustness. The SARS-COV-2 virus infection poses an immune system challenge that tests the organism's homeostatic response. Notably, the elderly and men are particularly vulnerable to severe disease, poor outcomes, and death. Mexico seems to have more infected young men than anywhere else. The goal of this study is to determine the differences in the relationships that link physiological variables that characterize the elderly and men, and those that characterize fatal outcomes in young men. To accomplish this, we examined a database of patients with moderate to severe COVID-19 (471 men and 277 women) registered at the "Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán" in March 2020. The sample was stratified by outcome, age, and sex. Physiological networks were built using 67 physiological variables (vital signs, anthropometric, hematic, biochemical, and tomographic variables) recorded upon hospital admission. Individual variables and system behavior were examined by descriptive statistics, differences between groups, principal component analysis, and network analysis. We show how topological network properties, particularly clustering coefficient, become disrupted in disease. Finally, anthropometric, metabolic, inflammatory, and pulmonary cluster interaction characterize the deceased young male group.

Plasma Total Antioxidant Capacity and Carbonylated Proteins Are Increased in Pregnant Women with Severe COVID-19.

Oxidative stress (OS) induced by SARS-CoV-2 infection may play an important role in COVID-19 complications. However, information on oxidative damage in pregnant women with COVID-19 is limited. Objective: We aimed to compare lipid and protein oxidative damage and total antioxidant capacity (TAC) between pregnant women with severe and non-severe COVID-19. Methods: We studied a consecutive prospective cohort of patients admitted to the obstetrics emergency department. All women positive for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction (RT-qPCR) were included. Clinical data were collected and blood samples were obtained at hospital admission. Plasma OS markers, malondialdehyde (MDA), carbonylated proteins (CP), and TAC; angiogenic markers, fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF); and renin-angiotensin system (RAS) markers, angiotensin-converting enzyme 2 (ACE-2) and angiotensin-II (ANG-II) were measured. Correlation between OS, angiogenic, and RAS was evaluated. Results: In total, 57 pregnant women with COVID-19 were included, 17 (28.9%) of which had severe COVID-19; there were 3 (5.30%) maternal deaths. Pregnant women with severe COVID-19 had higher levels of carbonylated proteins (5782 pmol vs. 6651 pmol; p = 0.024) and total antioxidant capacity (40.1 pmol vs. 56.1 pmol; p = 0.001) than women with non-severe COVID-19. TAC was negatively correlated with ANG-II (p < 0.0001) and MDA levels (p < 0.0001) and positively with the sFlt-1/PlGF ratio (p = 0.027). Conclusions: In pregnant women, severe COVID-19 is associated with an increase in protein oxidative damage and total antioxidant capacity as a possible counterregulatory mechanism.

Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity.

INTRODUCTION: Coronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined. METHODS: Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20 ng/ml (<50nmol/L) and deficient Vitamin D as a level ≤12 ng/ml (<30 nmol/L). RESULTS: Of the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p = 0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat. CONCLUSION: Vitamin D deficiency (≤12 ng/ml or <30 nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19.

Riesgo de progresión de COVID-19 severo mediante la escala call en un hospital público del norte de Perú / Risk of progression of severe COVID-19 through call scale in a public hospital in northern Peru

Establecer la validez diagnóstica de la escala CALL como predictor de mortalidad en pacientes con COVID-19 severo en Unidad de Cuidados Intensivos del Hospital Regional Docente de Trujillo desde abril del 2020 hasta julio del 2021. Material y métodos: Se llevó a cabo un estudio analítico, retrospectivo, en el cual se incluyeron a 177 pacientes con COVID-19 severo internados en Unidad de Cuidados Intensivos del Hospital Regional Docente de Trujillo, según criterios de selección, se calculó la escala CALL para cada uno y se asoció con la mortalidad encontrada; aplicándose la prueba estadística chi cuadrado; posteriormente se realizó un análisis de regresión multivariante para identificar los factores de riesgo asociados a la mortalidad. A su vez se utilizó el AUROC (área bajo la curva ROC) para establecer el rendimiento predictivo de la escala CALL. Resultados: De una muestra de 177 pacientes, al analizar la información mediante la curva ROC, se obtuvo un valor de corte 6 puntos para la escala CALL, con un área bajo la curva (AUC) de 0.612 (p=0,014); sensibilidad, especificidad, valor predictivo positivo y negativo de 86%, 29%, 60% y 62% respectivamente. No se encontraron diferencias significativas estadísticamente en cuanto a sexo, edad, shock séptico, SOFA, índice de comorbilidad de Charlson, necesidad de TRR ni compliance estática. En cambio, se evidenció asociación con la PaO2/FiO2(AU)

To establish the diagnostic validity of the CALL score as a predictor of mortality in patients with severe COVID-19 in the Intensive Care Unit of the Trujillo Regional Teaching Hospital from April 2020 to July 2021.Material and methods: An analytical, retrospective study was carried out, in which 177 patients with severe COVID-19 admitted to the Intensive Care Unit of the Regional Teaching Hospital of Trujillo were included, according to selection criteria, the CALL score was calculated for each one and was associated with the mortality found; applying the statistical chi 2 test; Subsequently, a multivariate regression analysis was performed to identify risk factors associated with mortality. In turn, the AUROC (area under the ROC curve) was used to establish the predictive performance of the CALL score. Results: From a sample of 177 patients, when analyzing the information using the ROC curve, a cut-off value of 6 points was obtained for the CALL score, with an area under the curve (AUC) of 0.612 (p=0.014); sensitivity, specificity, positive and negative predictive value of 86%, 29%, 60% and 62% respectively. No statistically significant differences were found in terms of sex, age, septic shock, SOFA, Charlson comorbidity index, need for renal replacement therapy (RRT) or static compliance. On the other hand, an association with PaO2 / FiO2 was evidenced(AU)

Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements.

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.