The usefulness of D-dimer as a predictive marker for mortality in patients with COVID-19 hospitalized during the first wave in Italy.

BackgroundThe coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Identification of predictors of poor outcomes will assist medical staff in treatment and allocating limited healthcare resources. AimsThe primary aim was to study the value of D-dimer as a predictive marker for in-hospital mortality. MethodsThis was a cohort study. The study population consisted of hospitalized patients (age >18 years), who were diagnosed with COVID-19 based on real-time PCR at 9 hospitals during the first COVID-19 wave in Lombardy, Italy (Feb-May 2020). The primary endpoint was in-hospital mortality. Information was obtained from patient records. Statistical analyses were performed using a Fine-Gray competing risk survival model. Model discrimination was assessed using Harrells C-index and model calibration was assessed using a calibration plot. ResultsOut of 1049 patients, 501 patients had evaluable data. Of these 501 patients, 96 died. The cumulative incidence of in-hospital mortality within 30 days was 20% (95CI: 16%-23%), and the majority of deaths occurred within the first 10 days. A prediction model containing D-dimer as the only predictor had a C-index of 0.66 (95%CI: 0.61-0.71). Overall calibration of the model was very poor. The addition of D-dimer to a model containing age, sex and co-morbidities as predictors did not lead to any meaningful improvement in either the C-index or the calibration plot. ConclusionThe predictive value of D-dimer alone was moderate, and the addition of D-dimer to a simple model containing basic clinical characteristics did not lead to any improvement in model performance.

Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study

Background and objectiveLong-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. MethodsIn this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected. ResultsBetween March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC [≥] 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities. ConclusionDLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae. Summary at a glanceDLCO and radiological assessment are the most sensitive tools to monitor COVID-19 patients at 6-month follow-up. Invasive ventilatory support is a risk factor for detection of radiological abnormalities, but not for DLCO impairment, at follow-up. Whileuse of prophylactic heparin acts as a protective factor on the development of DLCOimpairment.

Treat all COVID 19-positive patients, but do not forget those negative with chronic diseases.

The outbreak of coronavirus disease 2019 (COVID-19) has distressed our working practice. Infectious disease specialists, pneumologists and intensivists were not enough to face the enormous amount of patients that needed hospital care; therefore, many doctors have been recruited from other medical specialties trying to take care of as many patients as possible. The 'call to duty' of such doctors for urgent COVID-19 cases, however, diverted the attention from the care of patients with chronic conditions, which might have been neglected or undervalued. In this extremely difficult time, the standard of care of chronic patients has been reduced and this might have determined an increased rate of complications secondary to undermanagement. Thousands of patients with acute and chronic non-COVID-19 conditions have not accessed specialist care in the last weeks in Italy. Moreover, even those patients who have had scheduled an outpatient visit did not attend it for fear of leaving their home or due to the inability to go. During the pandemic, there was a drastic reduction in the number of hospital admissions for any medical conditions different from COVID-19. Self-presentation to the emergency department (ED) has been discouraged and the patients' own fear of being infected by going to the hospital led to also a significant decrease in ED access. During the lockdown, in San Giuseppe Hospital MultiMedica IRCCS, Milan, the ED admissions dropped from the mean of 2361/month in December 2019-February 2020 to 1102 (- 53%) and 861 (- 63%) in March and April 2020, respectively. For all the above-mentioned reasons, it is possible that some clinical conditions will further progress with a significant increase in morbidity and mortality. To prevent this, it is essential that patients with chronic conditions should be at least monitored and managed with telephone or online health consultation, identifying those who need urgent access to care, prioritizing outpatient visits based on disease severity. Patients with mild conditions could be managed outside the hospital by implementing telemedicine and creating networks of general practitioners who can consult with in-hospital specialists.

Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia

BackgroundIn hospitalized patients with COVID-19 pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for ICU and mortality. MethodsWe conducted a multicenter, observational study to explore the association between exposure to prolonged, low-dose, MP treatment and need for ICU referral, intubation or death within 28 days (composite primary endpoint) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. ResultsFindings are reported as MP (n=83) vs. control (n=90). The composite primary endpoint was met by 19 vs. 40 [adjusted hazard ratio (HR) 0.41; 95% confidence interval (CI): 0.24-0.72]. Transfer to ICU and need for invasive MV was necessary in 15 vs. 27 (p=0.07) and 14 vs. 26 (p=0.10), respectively. By day 28, the MP group had fewer deaths (6 vs. 21, adjusted HR=0.29; 95% CI: 0.12-0.73) and more days off invasive MV (24.0 {+/-} 9.0 vs. 17.5 {+/-} 12.8; p=0.001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the two groups (p=0.84). ConclusionIn patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Randomized controlled studies are needed to confirm these findings. RegistrationClinicalTrials.gov. Identifier: NCT04323592