Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.

PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

Clinical Presentation and Outcome of COVID-19 in a Latin American Versus Spanish Population: Matched Case-Control Study.

INTRODUCTION: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. RESULTS: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). CONCLUSION: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19.

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.

Impact of remdesivir according to the pre-admission symptom duration in patients with COVID-19.

BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Gustatory and olfactory dysfunctions in hospitalised patients with COVID-19 pneumonia: a prospective study.

IMPORTANCE: Identifying undetected clinical signs is imperative in the prevention of SARS-CoV-2. OBJECTIVE: To establish the prevalence of clinical gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. Clinical outcomes and recovery rates associated with gustatory and olfactory dysfunctions were also assessed. DESIGN: A prospective study was performed in 80 patients admitted to Hospital Clínic of Barcelona (Spain) for COVID-19 pneumonia. Patients were re-evaluated in the ward daily until discharge. Gustatory and olfactory dysfunction symptoms were retrospectively collected from emergency room (ER) charts after first assessments. Follow-up was performed in telemedicine consultation. SETTING: The single-centre study was performed in a hospitalisation ward at a university hospital. PARTICIPANTS: Consecutive patients meeting hospitalisation criteria for COVID-19 pneumonia were eligible. Study exclusion criteria were patients who could not speak, had previous gustatory and olfactory dysfunctions or whose PCR tests for SARS-CoV-19 were negative. INTERVENTIONS: Systematic assessment of gustatory and olfactory symptoms with standardised questions. OUTCOMES: Prevalence of gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. RESULTS: Of the 80 study subjects, 62.5% were male and the median age was 57 years. Half of the cohort (n=40) presented with comorbidities. The prevalence of chemosensitive disorder was 73.8% (n=59) (95% CI: 63.8 to 83.8), although self-reported symptoms were recorded in only 26.3% (n=21) of patients in the ER. Gustatory and olfactory dysfunctions were observed in 58.8% (n=47) and 55% (n=44) of cases, respectively. They were also the first symptoms in 25% (n=20) of patients. Anosmia was associated with ageusia, OR: 7, 95% CI: 2.3 to 21.8, p=0.001). No differences in clinical outcomes were observed when patients with and without gustatory and olfactory dysfunctions were compared. Recovery rates were 20% (n=10) and 85% (n=42) at days 7 and 45, respectively. CONCLUSION: The prevalence of gustatory and olfactory dysfunctions in COVID-19 pneumonia was much higher than in self-report. Presence of gustatory and olfactory dysfunctions was not a predictor of clinical outcomes.

Impact of Inflammatory Response Modifiers on the Incidence of Hospital-Acquired Infections in Patients with COVID-19.

INTRODUCTION: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19). METHODS: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case. RESULTS: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001). CONCLUSIONS: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk.

Long-Term Use of Tedizolid in Osteoarticular Infections: Benefits among Oxazolidinone Drugs.

BACKGROUND: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. METHODS: Multicentric retrospective study (January 2017-March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. RESULTS: Cases (n = 51; 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%); where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47; S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%); median treatment duration was 29 days (interquartile range -IQR- 15-44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079; and 240 × 109/L to 239 × 109/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%; among failures (n = 8), 63% were device-related infections. CONCLUSIONS: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections.

Ribotype 027 Clostridioides difficile infection presented as a traveller's diarrhoea / Infección por Clostridioides difficile Ribotipo 027 presentada como diarrea del viajero

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Fracción gamma del proteinograma y agudizaciones de la enfermedad pulmonar obstructiva crónica / Gamma globulin fraction of the proteinogram and chronic obstructive pulmonary disease exacerbations

Objetivos: Se pretende evaluar los niveles de la fracción de gammaglobulinas en suero como un marcador biológico para valorar la gravedad y predecir la mortalidad y nuevas agudizaciones en los pacientes ingresados por una agudización de la EPOC. Pacientes y métodos: El estudio VIRAE es una cohorte de pacientes ingresados por una agudización de probable causa infecciosa de la EPOC en un período de 2 años. Se analizaron los niveles de la fracción de gammaglobulinas del proteinograma en 120 pacientes. Se evaluaron los principales indicadores clínicos de gravedad. Se compararon las características principales en 2 grupos (mayor o menor de 6,6g/dl de la fracción gamma del proteinograma). Resultados: Los niveles de la fracción gamma del proteinograma se correlacionan con el valor del FEV1 (p=0,009), la PCR (p=0,04) y el número de reingresos a los 6 meses de la hospitalización (p=0,04). Se demuestra una buena asociación con la escala GOLD, el índice BODE y la escala de disnea de mMRC; y también con el tratamiento con corticoides orales y la oxigenoterapia domiciliaria. No hemos observado que sea un buen predictor de mortalidad, aun observando una mayor mortalidad al año del ingreso hospitalario en los pacientes con niveles bajos. Conclusiones: Los niveles de la fracción de gammaglobulinas en el proteinograma tienen una buena correlación con el FEV1. Además, se asocian a una mayor gravedad de los pacientes con EPOC. Este biomarcador sencillo puede ser útil para identificar pacientes de alto riesgo (AU)

Objectives: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD. Patients and methods: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl). Results: The levels of the serum gamma fraction in the proteinogram correlated with the FEV1 (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor. Conclusions: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV1. In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients (AU)

Gamma globulin fraction of the proteinogram and chronic obstructive pulmonary disease exacerbations. / Fracción gamma del proteinograma y agudizaciones de la enfermedad pulmonar obstructiva crónica.

OBJECTIVES: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD. PATIENTS AND METHODS: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl). RESULTS: The levels of the serum gamma fraction in the proteinogram correlated with the FEV1 (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor. CONCLUSIONS: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV1. In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients.