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.

Early 3-day course of remdesivir to prevent progression to severe Covid-19 in high-risk patients with hospital-acquired SARS-CoV-2 infection: preliminary results from two Italian outbreaks.

In multimorbid, unvaccinated and non-hospitalized patients, early administration of remdesivir, nirmatrelvir/ritonavir and molnupiravir was effective in reducing the risk of hospitalization or death from any cause. Similar data are lacking with regard to patients already hospitalized and who acquire in-hospital SARS-CoV-2 infection. We conducted a retrospective study during two outbreaks of SARS-CoV-2 infections involving 90 inpatients already hospitalized for medical or surgical conditions, in order to assess the effectiveness of early administration of remdesivir. Forty-seven cases were treated with a 3-day course of remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) within a median time of 1.4 day from testing positive, and were compared to a matched case-control cohort of 43 untreated patients; matching was based on age, sex, vaccination status, previous symptomatic infections by SARS-CoV-2, reasons for hospitalization (no significant differences). No case presented adverse events to remdesivir or death from COVID-19. No significant difference in overall in-hospital mortality was observed in cases compared to controls (17% vs 16.3%, p=0.925), but progression to severe pneumonia, although the difference was still not significant, showed an evident trend of a better outcome (8.5% vs 16.3%, p=0.261). Moreover, cases had a median discharge delay of 3 days (p=0.008).

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.

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

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.

Approach to patients with COVID-19 disease: the procedure in Udine

Coronavirus disease 2019 poses a serious threat to public health. The protocol developed at the Azienda Sanitaria Universitaria Friuli Centrale (Italy) is based on clinical data, laboratory tests, chest echography and HRCT. Several therapeutic options are considered, since patients vary in disease severity, evolution and co-morbidities and because so far there are no clear indications about therapeutic strategy based on randomized clinical trial. In this protocol chest echography has a central role in categorizing patient status, follow-up and decision-making.

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.

Approach to patients with COVID-19 disease: the procedure in Udine.

Coronavirus disease 2019 poses a serious threat to public health. The protocol developed at the Azienda Sanitaria Universitaria Friuli Centrale (Italy) is based on clinical data, laboratory tests, chest echography and HRCT. Several therapeutic options are considered, since patients vary in disease severity, evolution and co-morbidities and because so far there are no clear indications about therapeutic strategy based on randomized clinical trial. In this protocol chest echography has a central role in categorizing patient status, follow-up and decision-making.