Long pentraxin 3 as a marker of COVID-19 severity: evidences and perspectives.

Introduction: Several laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters. Materials and methods: Stored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay. Results: A total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P < 0.001). Univariate and multivariate logistic regression models demonstrated that the only significant laboratory predictor of ICU stay was PTX3 (OR: 1.68 (1.19-2.29), P = 0.003), after controlling for comorbidities. The Receiver Operator Characteristic curve analysis showed that PTX3 had a higher accuracy compared to C-reactive protein (CRP), lactate dehydrogenase (LD), ferritin in identifying ICU patients (AUC of PTX3 = 0.98; CRP = 0.66; LD = 0.70; ferritin = 0.67, P < 0.001). A cut-off of PTX3 > 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU. Conclusion: High values of PTX3 predict a more severe COVID-19.

SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy.

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high C-reactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment.

Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study.

BACKGROUND: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment. OBJECTIVES: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. METHODS: In this multicentre, prospective, observational cohort study, patients hospitalized 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," and "invasive mechanical ventilation") and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected. RESULTS: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range 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 restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities. CONCLUSIONS: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Syncope at SARS-CoV-2 onset.

We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) indicating hypocapnic hypoxemia. Patients who presented with syncope showed significantly lower heart rate as compared to 68 SARS-CoV-2 positive that did not. Such poorer than expected compensatory heart rate increase may have led to syncope based on individual susceptibility. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (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 intensive care unit (ICU) admission and mortality. METHODS: We 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 end point) 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. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In 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. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

Intensive care for seriously ill patients affected by novel coronavirus sars - CoV - 2: Experience of the Crema Hospital, Italy.

AIMS: In this work, the survival and mortality data of 54 consecutive patients admitted to the Intensive Care Unit (ICU) and suffering from severe respiratory insufficiency imputable to viral SARS - CoV - 2 infection were analyzed and shared, after a critical review of the evidence in order to optimize the most dedicated clinical and treatment strategy, for a future 'targeted' management in the care of the possible return flu outbreak. METHODS: At our Emergency Department of the Crema Hospital, from the beginning of the pandemic until the end of June 2020, 54 consecutive patients admitted to ICU suffering from severe acute respiratory infection (SARI) and severe respiratory distress (ARDS) attributable to viral SARS - CoV - 2 infection were recruited. The recruitment criterion was based on refractory hypoxia, general condition and clinical impairment, comorbidities and CT images. The incoming parameters of the blood chemistry and radiology investigations and the timing of the gold - tracheal intubation were compared. Medical therapy was based on the application of shared protocols. RESULTS: The onset of symptoms was varyng, i.e. within the range of 1-14 days. The average time from the admission to the emergency room to the admission to intensive care was approximately 120 h. The average number of days of hospitalization in the ICU was 28 days. With a majority of male patients, the most significant age group was between 60 and 69 years. There were 21 deaths and, compared to the survivors, the deceased ones were older at an average age of about 67 years (vs an average age of the survivors of about 59 years). From the available data entering the ICU, the surviving patients presented average better values of oximetry and blood gas analysis, with a lower average dosage of D-Dimer than the deceased. Ones with a presence of bilateral pneumonia in all patients, the worsening of the ARDS occurred in 31 patients. 9 out of 25 patients early intubated died, while 12 out of 23 patients died when intubation was performed after 24 h of non-invasive ventilation. The presence of multiple comorbidities was shown in 17 of 28 patients and revealed an additional adverse prognostic factor. Also, more than one complication in the same patient were detected; after respiratory worsening, renal failure was more frequently found in 16 patients. Some particular complications such as lesions induced by ventilation with barotrauma mechanism (VILI), ischemic heart disease and the appearance of central and peripheral neurological events were detected too. CONSIDERATIONS: SARS - CoV - 2 disease is caused by a new coronavirus that has its main route of transmission through respiratory droplets and close contact, resulting in a sudden onset of the clinical syndrome with acute respiratory infection (SARI) and severe respiratory distress (ARDS). But it can also appear with other symptoms such as gastrointestinal or neurological events, as to be considered as a disease with multisystem phenotype. This pathology evolves towards a serious form of systemic disease from an acute lung damage to venous and arterial thromboembolic complications and multi-organ failure, mostly associated with high mortality. All patients received empirical or targeted antibiotic therapy for prevention and control of infections of potential pathogens, together with low molecular weight heparin therapy. The majority of patients was subjected to the off - label protocol with antivirals and hydroxychloroquine therapy, we used cortisone support therapy under surveillance and in 3 cases the protocol with anti - IL6 monoclonal antibody (Tolicizumab). In a simplified classification of the tomographic examination of the chest, mostly 3D and 2C lesions were found in the deceased patients with a prevalence of severe and moderate forms, whilst in the survivors the distribution appears with a prevalence of medium and moderate forms. Among the intubated patients, 21 patients, all suffering from worsening ARDS, died whilst there was no mortality in patients subjected to non-invasive ventilation it so. The heterogeneity of the respiratory syndromes and the presence of multiple comorbidities represent an unfortunate prognostic factor. Among the complications, besides the respiratory worsening, renal failure, liver failure and the state of sepsis were most frequently found; less frequent complications were lesions induced by ventilation with a barotrauma mechanism, ischemic heart disease, the appearance of central neurological events of sensory alterations, meningo - encephalitis and cerebral hemorrhage, and peripheral neurological events with polyneuro - myopathies. Mechanical ventilation can adversely affect the prognosis due to lung damage induced, protective ventilation remains the necessary treatment during severe hypoxia in patients with SARS - CoV - 2. The essential prerequisite remains the search for optimal 'customized' values since conditions can vary from patient to patient and, in the same patient, during different times of ventilation. CONCLUSIONS: In these extraordinary circumstances, our reality was among the most affected and was able to hold the impact thanks to the immediate great response set in place by the operators, although it costed us an effort especially the one to try to guarantee a high quality level of assistance and care compared to the huge wave of patients in seriously bad conditions. Further research on this heterogeneous pathology and data sharing could help identify a more dedicated clinical decision-making and treatment pathway that, together with a resource planning, would allow us to better face any new disease outbreak.

Laboratory markers included in the Corona Score can identify false negative results on COVID-19 RT-PCR in the emergency room.

After December 2019 outbreak in China, the novel Coronavirus infection (COVID-19) has very quickly overflowed worldwide. Infection causes a clinical syndrome encompassing a wide range of clinical features, from asymptomatic or oligosymptomatic course to acute respiratory distress and death. In a very recent work we preliminarily observed that several laboratory tests have been shown as characteristically altered in COVID-19. We aimed to use the Corona score, a validated point-based algorithm to predict the likelihood of COVID-19 infection in patients presenting at the Emergency rooms. This approach combines chest images-relative score and several laboratory parameters to classify emergency room patients. Corona score accuracy was satisfactory, increasing the detection of positive patients' rate.

Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room.

Infection of novel Coronavirus has been declared pandemic by the WHO and now is a world public health crisis. Laboratory activity becames essential for the timely diagnosis. Few parameters, such Lymphocytes count, SaO2 and CRP serum level can be used to assess the severity of COVID-19 in emergency room.