Metabolic-associated fatty liver disease and liver fibrosis scores as COVID-19 outcome predictors: a machine-learning application.

Patients with COVID-19 and metabolic-dysfunction associated fatty liver disease (MAFLD) appear to be at higher risk for severe manifestations, especially in the youngest decades. Our aim was to examine whether patients with MAFLD and/or with increased liver fibrosis scores (FIB-4) are at risk for severe COVID-19 illness, using a machine learning (ML) model. Six hundred and seventy two patients were enrolled for SARS-CoV-2 pneumonia between February 2020 and May 2021. Steatosis was detected by ultrasound or computed tomography (CT). ML model valuated the risks of both in-hospital death and prolonged hospitalizations (> 28 days), considering MAFLD, blood hepatic profile (HP), and FIB-4 score. 49.6% had MAFLD. The accuracy in predicting in-hospital death was 0.709 for the HP alone and 0.721 for HP + FIB-4; in the 55-75 age subgroup, 0.842/0.855; in the MAFLD subgroup, 0.739/ 0.772; in the MAFLD 55-75 years, 0.825/0.833. Similar results were obtained when considering the accuracy in predicting prolonged hospitalization. In our cohort of COVID-19 patients, the presence of a worse HP and a higher FIB-4 correlated with a higher risk of death and prolonged hospitalization, regardless of the presence of MAFLD. These findings could improve the clinical risk stratification of patients diagnosed with SARS-CoV-2 pneumonia.

The Caliber of Segmental and Subsegmental Vessels in COVID-19 Pneumonia Is Enlarged: A Distinctive Feature in Comparison with Other Forms of Inflammatory and Thromboembolic Diseases.

BACKGROUND: The purpose of this study was to compare COVID-19 patients' vessel caliber with that of normal lungs and lungs affected by other inflammatory and thromboembolic processes. METHODS: between March and April 2020, 42 patients affected by COVID-19 pneumonia (COV-P) underwent CT scans of the lungs at Verona University Hospital for clinical indications. The lung images of four different groups of patients were compared (normal lung (NL), distal thromboembolism (DTE), and bacterial and fungal pneumonia (Bact-P, Fung-P)) by a radiologist with four years of experience. RESULTS: The COV-P patients' segmental and subsegmental vessels, evaluated as the ratio with the corresponding bronchial branch (V/B ratio), were larger, with respect to the NL the DTE groups, in the apparently healthy parenchyma, a result confirmed in the zones of opacification with respect to the Bact-P and Fung-P groups. CONCLUSIONS: This was the first study to show, by comparative analysis, that COVID-19 patients' segmental and subsegmental vessel calibers are significantly enlarged. This is a distinctive feature of COVID-19 pneumonia, suggesting its distinct pathophysiology as compared to other inflammatory and thromboembolic diseases and alerting radiologists to consider it when evaluating the CT scans of suspected patients.

Serology study after BTN162b2 vaccination in participants previously infected with SARS-CoV-2 in two different waves versus naïve.

Background: The antibody response to SARS-CoV-2 mRNA vaccines in individuals with waning immunity generated by a previous SARS-CoV-2 infection, as well as the patterns of IgA and IgM responses in previously infected and in naïve individuals are still poorly understood. Methods: We performed a serology study in a cohort of BTN162b2 mRNA vaccine recipients who were immunologically naïve (N, n = 50) or had been previously infected with SARS-CoV-2 (P.I., n = 51) during the first (n = 25) or second (n = 26) pandemic waves in Italy, respectively. We measured IgG, IgM and IgA antibodies against the SARS-CoV-2 Spike (S) and IgG against the nucleocapsid (N) proteins, as well as the neutralizing activity of sera collected before vaccination, after the first and second dose of vaccine. Results: Most P.I. individuals from the first pandemic wave who showed declining antibody titres responded to the first vaccine dose with IgG-S and pseudovirus neutralization titres that were significantly higher than those observed in N individuals after the second vaccine dose. In all recipients, a single dose of vaccine was sufficient to induce a potent IgA response that was not associated with serum neutralization titres. We observed an unconventional pattern of IgM responses that were elicited in only half of immunologically naïve subjects even after the second vaccine dose. Conclusions: The response to a single dose of vaccine in P.I. individuals is more potent than that observed in N individuals after two doses. Vaccine-induced IgA are not associated with serum neutralization.

Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

The persistence of neurological symptoms after SARS-CoV-2 infection, as well as the presence of late axonal damage, is still unknown. We performed extensive systemic and neurological follow-up evaluations in 107 out of 193 consecutive patients admitted to the COVID-19 medical unit, University Hospital of Verona, Italy between March and June 2020. We analysed serum neurofilament light chain (NfL) levels in all cases including a subgroup (n = 29) of patients with available onset samples. Comparisons between clinical and biomarker data were then performed. Neurological symptoms were still present in a significant number (n = 49) of patients over the follow-up. The most common reported symptoms were hyposmia (n = 11), fatigue (n = 28), myalgia (n = 14), and impaired memory (n = 11) and were more common in cases with severe acute COVID-19. Follow-up serum NfL values (15.2 pg/mL, range 2.4-62.4) were within normal range in all except 5 patients and did not differentiate patients with vs without persistent neurological symptoms. In patients with available onset and follow-up samples, a significant (p < 0.001) decrease of NfL levels was observed and was more evident in patients with a severe acute disease. Despite the common persistence of neurological symptoms, COVID-19 survivors do not show active axonal damage, which seems a peculiar feature of acute SARS-CoV-2 infection.

Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.

Importance of Cardiopulmonary Exercise Testing amongst Subjects Recovering from COVID-19.

The cardiopulmonary exercise test (CPET) provides an objective assessment of ventilatory limitation, related to the exercise minute ventilation (VE) coupled to carbon dioxide output (VCO2) (VE/VCO2); high values of VE/VCO2 slope define an exercise ventilatory inefficiency (EVin). In subjects recovered from hospitalised COVID-19, we explored the methodology of CPET in order to evaluate the presence of cardiopulmonary alterations. Our prospective study (RESPICOVID) has been proposed to evaluate pulmonary damage's clinical impact in post-COVID subjects. In a subgroup of subjects (RESPICOVID2) without baseline confounders, we performed the CPET. According to the VE/VCO2 slope, subjects were divided into having EVin and exercise ventilatory efficiency (EVef). Data concerning general variables, hospitalisation, lung function, and gas-analysis were also collected. The RESPICOVID2 enrolled 28 subjects, of whom 8 (29%) had EVin. As compared to subjects with EVef, subjects with EVin showed a reduction in heart rate (HR) recovery. VE/VCO2 slope was inversely correlated with HR recovery; this correlation was confirmed in a subgroup of older, non-smoking male subjects, regardless of the presence of arterial hypertension. More than one-fourth of subjects recovered from hospitalised COVID-19 have EVin. The relationship between EVin and HR recovery may represent a novel hallmark of post-COVID cardiopulmonary alterations.

Residual Lung Function Impairment Is Associated with Hyperventilation in Patients Recovered from Hospitalised COVID-19: A Cross-Sectional Study.

Patients who have recovered from COVID-19 show persistent symptoms and lung function alterations with a restrictive ventilatory pattern. Few data are available evaluating an extended period of COVID-19 clinical progression. The RESPICOVID study has been designed to evaluate patients' pulmonary damage previously hospitalised for interstitial pneumonia due to COVID-19. We focused on the arterial blood gas (ABG) analysis variables due to the initial observation that some patients had hypocapnia (arterial partial carbon dioxide pressure-PaCO2 ≤ 35 mmHg). Therefore, we aimed to characterise patients with hypocapnia compared to patients with normocapnia (PaCO2 > 35 mmHg). Data concerning demographic and anthropometric variables, clinical symptoms, hospitalisation, lung function and gas-analysis were collected. Our study comprised 81 patients, of whom 19 (24%) had hypocapnia as compared to the remaining (n = 62, 76%), and defined by lower levels of PaCO2, serum bicarbonate (HCO3-), carbon monoxide diffusion capacity (DLCO), and carbon monoxide transfer coefficient (KCO) with an increased level of pH and arterial partial oxygen pressure (PaO2). KCO was directly correlated with PaCO2 and inversely with pH. In our preliminary report, hypocapnia is associated with a residual lung function impairment in diffusing capacity. We focus on ABG analysis's informativeness in the follow-up of post-COVID patients.

Clinical risk scores for the early prediction of severe outcomes in patients hospitalized for COVID-19.

Coronavirus disease of 2019 (COVID-19) is associated with severe acute respiratory failure. Early identification of high-risk COVID-19 patients is crucial. We aimed to derive and validate a simple score for the prediction of severe outcomes. A retrospective cohort study of patients hospitalized for COVID-19 was carried out by the Italian Society of Internal Medicine. Epidemiological, clinical, laboratory, and treatment variables were collected at hospital admission at five hospitals. Three algorithm selection models were used to construct a predictive risk score: backward Selection, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest. Severe outcome was defined as the composite of need for non-invasive ventilation, need for orotracheal intubation, or death. A total of 610 patients were included in the analysis, 313 had a severe outcome. The subset for the derivation analysis included 335 patients, the subset for the validation analysis 275 patients. The LASSO selection identified 6 variables (age, history of coronary heart disease, CRP, AST, D-dimer, and neutrophil/lymphocyte ratio) and resulted in the best performing score with an area under the curve of 0.79 in the derivation cohort and 0.80 in the validation cohort. Using a cut-off of 7 out of 13 points, sensitivity was 0.93, specificity 0.34, positive predictive value 0.59, and negative predictive value 0.82. The proposed score can identify patients at low risk for severe outcome who can be safely managed in a low-intensity setting after hospital admission for COVID-19.

Asthma in a large COVID-19 cohort: Prevalence, features, and determinants of COVID-19 disease severity.

BACKGROUND: Asthma prevalence among COVID-19 patients seems to be surprisingly low. However the clinical profile of COVID-19 asthmatic patients and potential determinants of higher susceptibility/worse outcome have been scarcely investigated. We aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity. METHODS: Medical records of patients admitted to COVID-Units of six Italian cities major hospitals were reviewed. Demographic and clinical data were analyzed and compared according to the COVID-19 outcome (death/need for ventilation vs discharge at home without requiring invasive procedures). RESULTS: Within the COVID-Units population (n = 2000) asthma prevalence was 2.1%. Among the asthmatics the mean age was 61.1 years and 60% were females. Around half of patients were atopic, blood eosinophilia was normal in most of patients. An asthma exacerbation in the 6 months before the Covid-Unit admittance was reported by 18% of patients. 24% suffered from GINA step 4-5 asthma, and 5% were under biologic treatment. 31% of patients were not on regular treatment and a negligible use of oral steroid was recorded. Within the worse outcome group, a prevalence of males was detected (64 vs 29%, p = 0.026); they suffered from more severe asthma (43 vs 14%, p = 0.040) and were more frequently current or former smokers (62 vs 25%, p = 0.038). CONCLUSIONS: Our report, the first including a large COVID-19 hospitalized Italian population, confirms the low prevalence of asthma. On the other side patients with GINA 4/5 asthma, and those not adequately treated, should be considered at higher risk.

Cytomegalovirus-Induced Gastrointestinal Bleeding and Pancreatitis Complicating Severe Covid-19 Pneumonia: A Paradigmatic Case.

COVID-19 is a new pandemic disease whose pathophysiology and clinical description are still not completely defined. Besides respiratory symptoms and fever, gastrointestinal (GI) symptoms (including especially anorexia, diarrhea, and abdominal pain) represent the most frequent clinical manifestations. Emerging data point out that severe SARS-CoV-2 infection causes an immune dysregulation, which in turn may favor other infections. Here we describe a patient with severe COVID-19 pneumonia who developed in the resolving phase abdominal pain associated with cytomegalovirus (CMV)-induced duodenitis with bleeding and pancreatitis. A high level of suspicion toward multiple infections, including CMV, should be maintained in COVID-19 patients with heterogeneous clinical manifestations.