Evaluation of qualitative and semi-quantitative cut offs for rapid diagnostic lateral flow test in relation to serology for the detection of SARS-CoV-2 antibodies: findings of a prospective study.

BACKGROUND: There is limited information to compare the qualitative and semi-quantitative performance of rapid diagnostic tests (RDT) and serology for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the objective of the study was (a) to compare the efficacy of SARS-CoV-2 antibody detection between RDT and laboratory serology, trying to identify appropriate semi-quantitative cut-offs for RDT in relation with quantitative serology values and to (b) evaluate diagnostic accuracy of RDT compared to the NAAT gold standard in an unselected adult population. METHODS: SARS-CoV-2 antibodies were simultaneously measured with lateral flow immunochromatographic assays (LFA), the Cellex qSARS-CoV-2 IgG/IgM Rapid Test (by capillary blood), the iFlash-SARS-CoV-2 IgG/IgM chemiluminescent immunoassay (CLIA) (by venous blood) and the nucleic acid amplification test (NAAT) in samples from in- and out-patients with confirmed, suspected and negative diagnosis of coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) (March-May 2020). Interpretation of RDT was qualitative (positive/negative) and semi-quantitative based on a chromatographic intensity scale (negative, weak positive, positive). RESULTS: Overall, 720 paired antibody measures were performed on 858 patients. The qualitative and semiquantitative agreement analysis performed in the whole sample between LFA and CLIA provided a Kendall's tau of 0.578 (p < 0.001) and of 0.623 (p < 0.001), respectively, for IgM and IgG. In patients with a diagnosis of COVID-19, accordance between LFA and CLIA was maintained as a function of time from the onset of COVID-19 disease and the severity of disease both for qualitative and semi-quantitative assessments. RDT compared to the NAAT gold standard in 858 patients showed 78.5% sensitivity (95% CI 75.1%-81.7%) and 94.1% specificity (95% CI 90.4%-96.8%), with variable accordance depending on the timing from symptom onset. CONCLUSION: The RDT used in our study can be a non-invasive and reliable alternative to serological tests and facilitate both qualitative and a semi-quantitative antibody detection in COVID-19.

SARS-CoV-2 Vaccination in Solid-Organ Transplant Recipients.

The coronavirus disease 2019 (COVID-19) pandemic has posed significant global challenges for solid organ transplant (SOT) recipients. Mortality rates of COVID-19 in this patient population remain high, despite new available therapeutic options and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination. Priority access to SARS-CoV-2 vaccination for waitlisted candidates and for SOT patients and their family members is recommended since the advantage from vaccination reduces the risk of COVID-19-related complications. However, immunogenicity and efficacy of COVID-19 vaccines are lower in waitlisted candidates and SOT recipients than in the general population. Routine systematic assessment of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, although highly recommended for investigation and improvement of knowledge. SOT recipients should continue to adhere to preventive protective measures despite vaccination and may undergo passive antibody prophylaxis. This article seeks to provide an update on SARS-CoV-2 vaccination and preventive measures in SOT recipients based on existing literature and international guidelines.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

The impact of body composition on mortality of COVID-19 hospitalized patients: A prospective study on abdominal fat, obesity paradox and sarcopenia.

BACKGROUND & AIMS: Obesity has been described as a predisposing risk factor to severe forms of COVID-19, but conflicting results are emerging on its real impact on the mortality of COVID-19. We aimed to compare clinical outcomes and mortality among COVID-19 patients according to obesity, metabolic syndrome and adiposity distribution. METHODS: We conducted a prospective observational study of all consecutive adult patients with a confirmed diagnosis of SARS-CoV-2 infection admitted to the Infectious Diseases Clinic at Udine Hospital, Italy, from January 2021 to February 2021. At admission, the study population was submitted to specific anthropometric, laboratory and bioimpedance analysis (BIA) measurements and divided into five groups according to: 1) BMI < or >30 kg/m2; 2) waist circumference (WC) < or >98 cm for women, < or >102 cm for men; 3) presence or absence of metabolic syndrome (MS); 4) visceral adipose tissue (VAT) distribution; and 5) presence or absence of sarcopenia (SP) both based on BIA. We then compared clinical outcomes (ventilatory support, intensive care unit (ICU) admission, ICU length of stay, total hospital length of stay and mortality), immune and inflammatory makers and infectious and non-infectious acute complications within the five groups. RESULTS: A total of 195 patients were enrolled in the study. The mean age of patients was 71 years (IQR 61-80) and 64.6% (126) were male. The most common comorbidities were hypertension (55.9%) and MS (55.4%). Overall mortality was 19.5%. Abdominal adiposity, measured both with WC and with BIA, and SP were significantly associated with need for increased ventilator support (p = 0.013 for WC; p = 0.037, 0.027 and 0.009 for VAT; p = 0.004 and 0.036 for FMI; and p = 0.051 for SP), but not with ICU admission (WC p = 0.627, VAT p = 0.153, FMI p = 0.519 and SP p = 0.938), length of stay (WC p = 0.345, VAT p = 0.650, FMI p = 0.159 and SP p = 0.992) and mortality (WC p = 0.277, VAT p = 0.533, FMI p = 0.957 and SP p = 0.211). Obesity and MS did not discriminate for the intensity of ventilatory outcome (p = 0.142 and p = 0.198, respectively), ICU admission (p = 0.802 and p = 0.947, respectively), length of stay (p = 0.471 and p = 0.768, respectively) and mortality (p = 0.495 and p = 0.268, respectively). We did not find significant differences in inflammatory markers and secondary complications within the five groups. CONCLUSIONS: In patients admitted with COVID-19, increased WC, visceral abdominal fat and SP are associated with higher need for ventilatory support. However, obesity, MS, SP and abdominal adiposity are not sensitive predictive factors for mortality.

Improving management and antimicrobial stewardship for bacterial and fungal infections in hospitalized patients with COVID-19.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection is being one of the most significant challenges of health care systems worldwide. Bacterial and fungal infections in hospitalized patients with coronavirus disease 2019 (COVID-19) are uncommon but consumption of antibiotics and antifungals has increased dramatically during the ongoing pandemic resulting in increased selective pressure for global antimicrobial resistance. Nosocomial bacterial superinfections appear to be more frequent than community-acquired coinfections, particularly among patients admitted to the intensive care unit (ICU) and those receiving immunosuppressive treatment. Fungal infections associated with COVID-19 might be missed or misdiagnosed. Existing and new antimicrobial stewardship (AMS) programmes can be utilized directly in COVID-19 pandemic and are urgently needed to contain the high rates of misdiagnosis and antimicrobial prescription. The aim of this review is to describe the role of bacterial and fungal infections and possible strategies of AMS to use in daily practice for optimal management of COVID-19.

One Word to Describe My Experience as a COVID-19 Survivor Six Months after Its Onset: Findings of a Qualitative Study.

The COVID-19 pandemic emotionally affected the lives of patients cared for in different settings. However, a comprehensive view of the whole experience as lived by survived patients, from the onset of the disease and over time, is substantially unknown to date. A descriptive qualitative design was implemented according to the Standards for Reporting Qualitative Research. Adult patients (=1067) cared for during the first wave (March/April 2020) capable of answering an interview and willing to participate were interviewed (=397) by phone with an interview guide including open- and closed-ended questions. In this context, they were asked to summarise with a metaphor their entire COVID-19 experience at six months. Then, the emotional orientation (positive, neutral, or negative) of the metaphors expressed was identified. The participants were mainly female (206; 51.9%), with an average age of 52.6 years (CI 95% 50.4-53.6), reporting a mild severity of COVID-19 disease at the onset (261; 65.7%) and the perception of being completely healed (294; 70%) at six months. The patients summarised their experiences mainly using negative-oriented (248; 62.5%) metaphors; only 54 (13.6%) reported positive-oriented metaphors and a quarter (95; 23.95) neutral-oriented metaphors. Nearly all positive-oriented metaphors were reported by patients with symptoms at the onset (53; 98.1%), a significantly higher proportion compared to those reporting negative- (219; 88.3%) and neutral-oriented (78; 82.1%) metaphors (p = 0.014). While no other clinical features of the disease were associated, among females, significantly more negative-oriented metaphors emerged. Moreover, neutral-oriented metaphors were reported by younger patients (49.5 years, CI 95% 64.11-52.92) as compared to those negative and positive that were reported by more mature patients (53.9; CI 95% 52.04-55.93 and 54.8; CI 95% 50.53-59.24, respectively) (p = 0.044). Nurses and healthcare services require data to predict the long-term needs of patients. Our findings suggest that, for many patients, the COVID-19 lived experience was negative over time.

Post-COVID-19 syndrome and humoral response association after one year in vaccinated and unvaccinated patients

Objectives To describe the impact of vaccination and the role of humoral responses on post-coronavirus disease 2019 (COVID-19) syndrome one year after the onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods A prospective study. Interviews investigated post-COVID-19 syndrome 6 and 12 months after the disease onset of all adult in- and outpatients with COVID-19 attending Udine Hospital (March–May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain –RBD SARS-CoV-2 IgG) and/or natural infection (non-RBD- SARS-CoV-2 IgG) were also assessed. Results 479 individuals (52.6% female, mean age 53 years) were interviewed 13.5 months (0.6 SD) after acute infection. Post-COVID-19 syndrome was observed in 47.2% (226/479) of patients after one year. There were no significant differences in the worsening of post-COVID 19 symptoms (22.7% vs 15.8%, p = 0.209) among vaccinated (n=132) and unvaccinated (n=347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR 1.35, 95% CI 1.11–1.64, p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long-haulers than in patients without symptoms 22 (IQR 9.7–37.2) vs 14.1 (IQR 5.4–31.3) kAU/L, p = 0.009) after one year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs 0.9–2500 U/mL, OR 1.36, 95% CI 0.62–3.00, p = 0.441) and RBD SARS-CoV-2 IgG titres were similar in long-haulers than in patients without symptoms (50% values > 2500 U/mL vs 55.6% values > 2500 U/mL, p = 0.451) Conclusions The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms over one year after acute infection. The persistence of high serological titres response induced by natural infection but not by vaccination, may play a role in long-COVID-19. Graphical Image 1

Prognostic Role of Malnutrition Diagnosed by Bioelectrical Impedance Vector Analysis in Older Adults Hospitalized with COVID-19 Pneumonia: A Prospective Study.

BACKGROUND: Little is known on the clinical relevance of the nutritional status and body composition of patients hospitalized with SARS-CoV-2 infection. The aim of our study was to assess the prevalence of malnutrition in patients with COVID-19 pneumonia using bioelectrical impedance vector analysis (BIVA), and to evaluate the relationship of their nutritional status with the severity and outcome of disease. METHODS: Among 150 consecutive patients who were hospitalized with COVID-19 pneumonia, 37 (24.3%) were classified as malnourished by BIVA, and were followed-up for 60 days from admission. Outcome measures were differences in the need for invasive mechanical ventilation, in-hospital mortality, and the duration of hospital stay in survivors. RESULTS: During 60 days of follow-up, 10 (27%) malnourished patients and 13 (12%) non-malnourished patients required invasive mechanical ventilation (p = 0.023), and 13 (35%) malnourished patients and 9 (8%) non-malnourished patients died (p < 0.001). The average duration of the hospital stay in survivors was longer in patients with malnutrition (18.2 ± 15.7 vs. 13.2 ± 14.8 days, p < 0.001). In survival analyses, mechanical ventilation free (log-rank 7.887, p = 0.050) and overall (log-rank 17.886, p < 0.001) survival were significantly longer in non-malnourished than malnourished patients. The Cox proportional ratio showed that malnutrition was associated with an increased risk of mechanical ventilation (HR 4.375, p = 0.004) and death (HR 4.478, p = 0.004) after adjusting for major confounders such as age, sex, and BMI. CONCLUSIONS: Malnutrition diagnosed with BIVA was associated with worse outcomes in hospitalized patients with COVID-19 pneumonia.

The Fall in Antibody Response to SARS-CoV-2: a Longitudinal Study of Asymptomatic to Critically Ill Patients Up to 10 Months after Recovery.

The aim of this study was to assess the long-term dynamics and factors associated with the serological response against the severe acute respiratory syndrome coronavirus 2 after primary infection. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), mostly with mild COVID-19 (370, 68.3%). Patients were followed for a median of 302 days (interquartile range, 186 to 311). The overall seroconversion rate within 2 months was 32% for IgM and 90% for IgG. Seroreversion was observed in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of long-term immunity both for IgM (ß, linear regression coefficient, 1.10, P = 0.001; ß 5.15 P = 0.014; ß 43.84 P = 0.021, respectively) and for IgG (ß 1.43 P < 0.001; ß 10.46 P < 0.001; ß 46.79 P < 0.001, respectively), whereas the initial IgG peak was associated only with IgG duration (ß 1.12, P < 0.001). IgM antibodies disappeared at 4 months, and IgG antibodies declined in about half of patients 10 months after acute COVID-19. These effects varied depending on the intensity of the initial antibody response, age, and burden of acute COVID-19.

Low risk of reinfections and relation with serological response after recovery from the first wave of COVID-19.

The aim of the study was to assess reinfection rates in relation to long-term antibody dynamics against SARS-CoV-2 after the first wave. A prospective longitudinal study with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. During the follow-up, reinfections were collected. A total of 546 unselected individuals with COVID-19 acquired from March to May 2020 were included (292 female, mean age 53 years). After a median follow-up of 10 months (IQR 6.2-10.4), reinfection occurred in 6 (1.1%) patients, median age of 44.5 years (IQR 33‒49). All had a previous history of mild COVID-19 (all were healthcare workers) and reinfection occurred a median of 9 months (IQR 8.2‒10.2) after the onset of the first episode. Patients with reinfection were either seronegative (2/56, n = 3.6%), seroreverted (2/137, 1.5%), or seropositive (2/353, 0.6%) (p = 0.085). All reinfections were mild (n = 5) or asymptomatic (n = 1). After reinfection, none of patients developed IgM response and only two had a transitory boosted IgG immunization response. In an unselected population after the first wave of COVID-19, after a prolonged observation period (mean 10 months), reinfection was very uncommon; occurred in patients with a previous history of mild infection, mostly with weak or absent serological response; and manifested with mild or asymptomatic clinical presentation.

Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients.

OBJECTIVES: To assess the prevalence of and factors associated with post-coronavirus disease 2019 (COVID-19) syndrome 6 months after the onset. METHODS: A bidirectional prospective study. Interviews investigated symptoms potentially associated with COVID-19 6 months after the disease onset of all consecutive adult inpatients and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. IgG antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were also evaluated 6 months after the onset of symptoms, at the time of the interview. RESULTS: A total of 599 individuals were included (320 female, 53.4%; mean age 53 years, SD 15.8) and interviewed 187 days (22 SD) after onset. The prevalence of post-COVID-19 syndrome was 40.2% (241/599). The presence of IgG antibodies was significantly associated with the occurrence of post-COVID-19 syndrome (OR 2.56, 95% CI 1.48-4.38, p 0.001) and median SARS-CoV-2 IgG titres were significantly higher in patients with post-COVID-19 syndrome than in patients without symptoms (42.1, IQR 17.1-78.4 vs. 29.1, IQR 12.1-54.2 kAU/L, p 0.004). Female gender (OR 1.55, 95% CI 1.05-2.27), a proportional increase in the number of symptoms at the onset of COVID-19 (OR 1.81, 95% CI 1.59-2.05) and ICU admission OR 3.10, 95% CI 1.18-8.11) were all independent risk factors for post-COVID-19 syndrome. The same predictors also emerged in a subgroup of 231 patients with the serological follow-up available at the time of the interview alongside the proportional increase in anti-SARS-CoV-2 IgG (OR 1.01, 95% CI 1.00-1.02, p 0.04). DISCUSSION: Prospective follow-up could be offered to specific subgroups of COVID-10 patients, to identify typical symptoms and persistently high anti-SARS-CoV-2 IgG titres as a means of early detection of post-COVID-19 long-term sequelae.

Vaccine Hesitancy among Italian Patients Recovered from COVID-19 Infection towards Influenza and Sars-Cov-2 Vaccination.

We aimed to assess the attitude towards influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations among coronavirus disease 2019 (COVID-19) recovered patients. We performed a cross-sectional study consisting of a standardized telephone interview carried out between September and November 2020 targeting a cohort of adult in- and out-patients that had recovered from COVID-19 after the first wave (March-May 2020) at Udine Hospital (Italy). Overall, 599 people participated (320 female, median age 53 years) and most had experienced an acute COVID-19 with mild illness (409, 68.3%). The majority were hesitant or undecided towards influenza (327, 54.6%) and SARS-CoV-2 (353, 59.2%) vaccines. Older age, public work exposure, and previous 2019 flu shots were the main factors associated with a positive attitude toward both vaccinations (p < 0.05). Being hospitalized during the acute COVID-19 phase was associated with the willingness to get a flu shot (94/272, 34.5%) but not SARS-CoV-2 vaccine (70/244, 28.7%). Vaccine hesitancy is diffuse and multifactorial also among COVID-19 recovered.

MR-proADM as prognostic factor of outcome in COVID-19 patients.

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.