Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

BACKGROUND: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. METHODS: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. RESULTS: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). CONCLUSIONS: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Mental health symptoms one year after acute COVID-19 infection: Prevalence and risk factors.

Introduction: Emerging evidence suggests that mental health symptoms in COVID-19 survivors are higher than expected, possibly indicating that such symptoms are more likely to develop post-infection than just persist as a residual component of the acute phase. It is thus imperative to investigate the potential development of a post-COVID mental health syndrome in the longer-term and identify its risk factors. Material and methods: A prospective study investigated mental health symptoms associated with COVID-19 and its determinants over a 12-month period following the disease onset in all consecutive adult inpatients and outpatients with COVID-19 attending a tertiary referral hospital from March to May 2020. Results: A total of 479 patients (female, 52.6%) were followed-up for 12 months after COVID-19 onset. Of them, 47.2% were still presenting with at least one symptom. While most symptoms subsided as compared to COVID-19 onset (all p < 0.001), a significant increase was observed only for symptoms of psychiatric disorders (10.2%) and lack of concentration and focus (20%; all p < 0.001). Patients presenting with symptoms related to multiple body systems 12 months after contracting COVID-19 (all p ≤ 0.034) were more likely to suffer from mental health domain-related symptoms at follow-up. Also, a higher risk of presenting with lack of concentration and focus 12 months post infection was found in those suffering of psychiatric symptoms at COVID-19 onset (p = 0.005). Conclusions: Findings of this study may have important public health implications, as they underlie the increased need for mental health support in COVID-19 survivors.

Introducción: Nuevas evidencias sugieren que los síntomas de salud mental en los supervivientes de COVID-19 son mayores de lo esperado, lo que posiblemente indica que es más probable que dichos síntomas se desarrollen después de la infección en vez de sólo persistir como componente residual de la fase aguda. Por lo tanto, es imperativo investigar el posible desarrollo de un síndrome de salud mental post-COVID a largo plazo e identificar sus factores de riesgo. Materiales y métodos: Un estudio prospectivo investigó los síntomas de salud mental asociados a la COVID-19 y sus determinantes durante un periodo de 12 meses tras el inicio de la enfermedad en todos los pacientes adultos consecutivos con COVID-19, hospitalizados y ambulatorios, que acudieron a un hospital de tercer nivel entre marzo y mayo de 2020. Resultados: Un total de 479 pacientes (mujeres, 52,6%) fueron seguidos durante 12 meses después del inicio de COVID-19. De ellos, el 47,2% seguía presentando al menos un síntoma. Mientras que la mayoría de los síntomas disminuyeron en comparación con el inicio de la COVID-19 (todos p < 0,001), se observó un aumento significativo solamente de los síntomas de los trastornos psiquiátricos (10,2%) y la falta de concentración y enfoque (20%; todos p < 0,001). Los pacientes que presentaban síntomas relacionados con múltiples sistemas del cuerpo 12 meses después de contraer la COVID-19 (todos p ≤ 0,034) tenían más probabilidades de sufrir síntomas relacionados con el dominio de la salud mental en el seguimiento. Además, se encontró un mayor riesgo de presentar falta de concentración y enfoque 12 meses después de la infección en los que sufrían síntomas psiquiátricos al inicio de COVID-19 (p = 0,005). Conclusiones: Los resultados de este estudio pueden tener importantes implicaciones para la salud pública, ya que subyacen a la mayor necesidad de apoyo a la salud mental de los supervivientes de COVID-19.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study).

BACKGROUND: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. METHODS: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. RESULTS: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). CONCLUSIONS: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. TRIAL REGISTRATION: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Quality of Life in COVID-Related ARDS Patients One Year after Intensive Care Discharge (Odissea Study): A Multicenter Observational Study.

BACKGROUND: Investigating the health-related quality of life (HRQoL) after intensive care unit (ICU) discharge is necessary to identify possible modifiable risk factors. The primary aim of this study was to investigate the HRQoL in COVID-19 critically ill patients one year after ICU discharge. METHODS: In this multicenter prospective observational study, COVID-19 patients admitted to nine ICUs from 1 March 2020 to 28 February 2021 in Italy were enrolled. One year after ICU discharge, patients were required to fill in short-form health survey 36 (SF-36) and impact of event-revised (IES-R) questionnaire. A multivariate linear or logistic regression analysis to search for factors associated with a lower HRQoL and post-traumatic stress disorded (PTSD) were carried out, respectively. RESULTS: Among 1003 patients screened, 343 (median age 63 years [57-70]) were enrolled. Mechanical ventilation lasted for a median of 10 days [2-20]. Physical functioning (PF 85 [60-95]), physical role (PR 75 [0-100]), emotional role (RE 100 [33-100]), bodily pain (BP 77.5 [45-100]), social functioning (SF 75 [50-100]), general health (GH 55 [35-72]), vitality (VT 55 [40-70]), mental health (MH 68 [52-84]) and health change (HC 50 [25-75]) describe the SF-36 items. A median physical component summary (PCS) and mental component summary (MCS) scores were 45.9 (36.5-53.5) and 51.7 (48.8-54.3), respectively, considering 50 as the normal value of the healthy general population. In all, 109 patients (31.8%) tested positive for post-traumatic stress disorder, also reporting a significantly worse HRQoL in all SF-36 domains. The female gender, history of cardiovascular disease, liver disease and length of hospital stay negatively affected the HRQoL. Weight at follow-up was a risk factor for PTSD (OR 1.02, p = 0.03). CONCLUSIONS: The HRQoL in COVID-19 ARDS (C-ARDS) patients was reduced regarding the PCS, while the median MCS value was slightly above normal. Some risk factors for a lower HRQoL have been identified, the presence of PTSD is one of them. Further research is warranted to better identify the possible factors affecting the HRQoL in C-ARDS.

VENTILATORY ASSOCIATED BAROTRAUMA IN COVID-19 PATIENTS: A MULTICENTER OBSERVATIONAL CASE CONTROL STUDY (COVI-MIX-STUDY)

Background The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence;we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. Methods This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. Results We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients;these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). Conclusions C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma;otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. Trial registration this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

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.

Sleep alterations following COVID-19 are associated with both neuroinflammation and psychological disorders, although at different times.

Introduction: By the end of 2019, severe acute respiratory syndrome coronavirus 2 rapidly spread all over the world impacting mental health and sleep habits. Insomnia, impaired sleep quality, and circadian rhythm alterations were all observed during the pandemic, especially among healthcare workers and in patients with acute and post-acute COVID-19. Sleep disruption may induce a pro-inflammatory state associated with an impairment of immune system function. Objective: We investigated the relationship between sleep alterations, psychological disorders, and inflammatory blood biomarkers in patients with post-acute COVID-19. Methods: We enrolled 47 subjects diagnosed with COVID-19 pneumonia at Santa Maria della Misericordia University Hospital (Udine, Italy) between March and May 2020. Selected patients were evaluated at 2 months (T1) and 10 months (T2) after discharge. Each time, we collected clinical interviews, neurological examinations, and self-administered questionnaires to assess sleep and life quality, anxiety, depression, and post-traumatic stress disorder. Blood biomarkers of endothelial activation, neuroinflammation, and inflammatory cytokines were also measured at each follow-up. Collected variables were analyzed using comparisons between groups and linear regression models. Results: Prevalence of insomnia increased from 10.6% up to 27.3% after COVID-19. Poor sleep quality was found in 41.5% of patients at both study visits. At T1 follow-up, poor sleepers showed higher levels of neurofilament light chain, vascular cell adhesion molecule 1, and interleukin 10; no significant associations were found between sleep quality and psychological disorders. At T2 follow-up, lower sleep quality was associated with higher levels of vascular cell adhesion molecule 1 and interleukin 8, but also with higher scores for anxiety, depression, and post-traumatic stress disorder. Conclusion: Our results suggest an association of poor sleep quality with both psychological disorders and neuroinflammation, although at different times, in previously hospitalized patients with moderate-to-critical COVID-19.

Combining Deep Phenotyping of Serum Proteomics and Clinical Data via Machine Learning for COVID-19 Biomarker Discovery.

The persistence of long-term coronavirus-induced disease 2019 (COVID-19) sequelae demands better insights into its natural history. Therefore, it is crucial to discover the biomarkers of disease outcome to improve clinical practice. In this study, 160 COVID-19 patients were enrolled, of whom 80 had a "non-severe" and 80 had a "severe" outcome. Sera were analyzed by proximity extension assay (PEA) to assess 274 unique proteins associated with inflammation, cardiometabolic, and neurologic diseases. The main clinical and hematochemical data associated with disease outcome were grouped with serological data to form a dataset for the supervised machine learning techniques. We identified nine proteins (i.e., CD200R1, MCP1, MCP3, IL6, LTBP2, MATN3, TRANCE, α2-MRAP, and KIT) that contributed to the correct classification of COVID-19 disease severity when combined with relative neutrophil and lymphocyte counts. By analyzing PEA, clinical and hematochemical data with statistical methods that were able to handle many variables in the presence of a relatively small sample size, we identified nine potential serum biomarkers of a "severe" outcome. Most of these were confirmed by literature data. Importantly, we found three biomarkers associated with central nervous system pathologies and protective factors, which were downregulated in the most severe cases.

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.

Impact of Cryopreservation of Peripheral Blood Stem Cells (PBSC) in Transplantation from Matched Unrelated Donor (MUD).

Background: Cryopreservation of PBSC for allogenic hematopoietic stem cell transplantation (allo-HSCT) was implemented due to the current Coronavirus 2019 pandemic. The impact of match unrelated donor (MUD) graft freezing on the outcome of allo-HSCT in terms of hematological recovery, graft versus host disease (GVHD), and survival are still controversial. Methods: In this study, we compared graft composition, clinical characteristics, and outcome of 31 allo-HSCT from MUD cryopreserved PBSC (Cryo Group) with 23 matched-pair allo-HSCT from fresh MUD PBSC (Fresh Group) performed in our center between January 2020 and July 2021. Results: No significant differences were recognized in clinical characteristics of patients, donors, and transplants between the Cryo and Fresh groups except for a better prognostic comorbidity index (HCT-CI) of the Cryo group. In the Cryo Group, the median time from apheresis to cryopreservation was 46.0 h (range 23.8-53.5), while the median time from cells collection and reinfusion was 13.9 days (range 5.8-28.1). In the Fresh Group, median time from apheresis to reinfusion was 35.6 h (range 21.4-51.2). The number of viable (7-AAD negative) CD34+ cells per kg patient infused was significantly lower in the Cryo Group (5.2 ± 1.9 × 106/kg vs. 7.0 ± 1.3 × 106/kg; p < 0.001). Indeed, there was a 36% (11-70) median loss of viable CD34+/kg cells after freezing. All patients engrafted: median time to neutrophil engraftment (>0.5 × 109/L) was 13.5 days (range 12-15) for Cryo Group and 14 days (range 13-16) days for Fresh Group (p = 0.522), while the median time to platelet engraftment (>20 × 109/L) was, respectively, 14 (range 12-18) and 15 (range 12-17) days (p = 0.904). The incidence of grade ≥ 2 acute GVHD was similar in the two groups (56.5% Cryo Group vs. 60.0% Fresh Group; p = 0.832) and no differences in terms of OS (p = 0.090), PFS (p = 0.200) and TRM (p = 0.970) were observed between the Cryo and Fresh groups. Conclusions: In our series, no differences between the Cryo and Fresh groups were found in engraftment, grade ≥ 2 acute GVHD incidence, OS, PFS, and TRM despite a lower CD34+ infused dose in the Cryo Group. Frozen PBSCs could be considered a safe option also for allo-HSCT from MUD but a higher amount of PBSC should be collected to warrant an adequate viable CD34+ post-thawing.

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

Validation of a Saliva-Based Test for the Molecular Diagnosis of SARS-CoV-2 Infection.

BACKGROUND: Since the beginning of the pandemic, clinicians and researchers have been searching for alternative tests to improve the screening and diagnosis of the SARS-CoV-2 infection. Currently, the gold standard for virus identification is the nasopharyngeal (NP) swab. Saliva samples, however, offer clear, practical, and logistical advantages but due to a lack of collection, transport, and storage solutions, high-throughput saliva-based laboratory tests are difficult to scale up as a screening or diagnostic tool. With this study, we aimed to validate an intralaboratory molecular detection method for SARS-CoV-2 on saliva samples collected in a new storage saline solution, comparing the results to NP swabs to determine the difference in sensitivity between the two tests. METHODS: In this study, 156 patients (cases) and 1005 asymptomatic subjects (controls) were enrolled and tested simultaneously for the detection of the SARS-CoV-2 viral genome by RT-PCR on both NP swab and saliva samples. Saliva samples were collected in a preservative and inhibiting saline solution (Biofarma Srl). Internal method validation was performed to standardize the entire workflow for saliva samples. RESULTS: The identification of SARS-CoV-2 conducted on saliva samples showed a clinical sensitivity of 95.1% and specificity of 97.8% compared to NP swabs. The positive predictive value (PPV) was 81% while the negative predictive value (NPV) was 99.5%. Test concordance was 97.6% (Cohen's Kappa = 0.86; 95% CI 0.81-0.91). The LoD of the test was 5 viral copies for both samples. CONCLUSIONS: RT-PCR assays conducted on a stored saliva sample achieved similar performance to those on NP swabs, and this may provide a very effective tool for population screening and diagnosis. Collection of saliva in a stabilizing solution makes the test more convenient and widely available; furthermore, the denaturing properties of the solution reduce the infective risks belonging to sample manipulation.

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.