Evaluation of Early Diagnosis of COVID-19 Algorithms

The coronavirus disease 2019 (COVID-19) has been stated as a global pandemic, and the BA.4 and BA.5 variants are anticipated to drive the next wave of COVID-19 infection. Early diagnosis of this infection reduces its viral excretion. In this paper, after a large study of existing algorithms for pre-symptomatic COVID-19 detection in the state-of-the-art, we discovered a notable flaw in most models related to the choice of the evaluation function, such that, all the tested algorithms perform worse (from the evaluation function perspective) than an algorithm that generates alarms randomly from a binomial distribution. Therefore, we propose a simple and less biased evaluation function to better compare the quality of different algorithms. Comprehensive experimental evaluations of the state-of-the-art algorithms over the real-world dataset published by Nature Medicine journal contains 84 COVID-19 patients and 2,000 healthy participants show the effectiveness and the relevance of our evaluation method. Moreover, the proposed framework is released as an open-source library. © 2022 IEEE.

Understanding daily psychological well-being in the context of the early COVID-19 environment

The onset of the COVID-19 pandemic led to a pervasive environment that was both novel and unescapable for people everywhere. This prolonged and massive event operated across multiple levels of influence with impacts ranging from the most distal global environment to the most proximal immediate environment of daily life. Individuals had to deal with wide-spread challenges and uncertainties, including coping with stay-at-home orders, adapting to new safety requirements and policies, and facing fear and risk of infection as well as symptoms from the virus itself. In order to investigate the impacts of this environment on daily psychological well-being, this dissertation identified innovative environmental measures of that COVID-19 environment and connected them to individuals' ecological momentary assessment outcomes, bridging community level indicators with person level experiences. This work addressed a critical gap in the COVID-19 literature, namely that COVID-19 pandemic was not a monolithic experience but a dynamic and complex environment. Specifically, Study 1 examined the role of daily changes in COVID-19 severity at the state level by using reported cases and deaths in February and March of 2020 to predict daily distress and distress variability in emerging adults. It also considered the differential effects of accumulated cases (or deaths) and daily new cases (or deaths). Study 2 examined relationships between community level COVID-19 information seeking and individual worry and coping self-efficacy. Internet search data was used as an indicator of community information seeking based on high interest search terms related to COVID-19 and critical lockdown material resources. Findings from both studies provide support for the role of the COVID-19 environment in daily well-being at multiple levels of influence. Distress, worry, and coping all showed evidence of environmental influences. Additionally, this work supports the critical need for investigating environments and their connections over time in models that allow both the environment and the individuals to change. This work has implications for understanding the complicated well-being effects of the COVID-19 environment and findings can be expanded to other crisis and chronic stress environments. It also provides a model for more precise within-person research that better models and measures environments and the impact of those environments on key individual health and well-being outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The impact of early therapies for COVID-19 on death, hospitalization and persisting symptoms: a retrospective study.

PURPOSE: Oral antivirals (nirmatrelvir/ritonavir and molnupiravir), intravenous short treatment of remdesivir and anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been used for early COVID-19 treatments in high risk of disease progression patients. The term long COVID has been used to refer to a range of new, returning, or ongoing symptoms after SARS-CoV-2 infection. Little is known about the impact of such therapies on long COVID. METHODS: This is a retrospective observational study, including all outpatients evaluated from April 2021 to March 2022 in Brescia, Lombardy, northern Italy. Patients were stratified in three groups: (a) treated with mAbs, (b) treated with antivirals drugs and (c) controls (patients eligible for a or b who refused treatment). Data were collected at baseline and at month 1 and 3 (data on self-reported symptoms were collected using a telephone-administered questionnaire). We assessed early COVID-19 therapies effectiveness in preventing hospitalization, death at 1 or 3 months and persisting symptoms at 3 months after the onset of SARS-CoV-2 infection. RESULTS: A total of 649 patients were included in the study, of which 242 (37.3%) were treated with mAbs, 197 (30.3%) with antiviral drugs and 210 (32.4%) were not treated. Patients most frequently reported cerebro-cardiovascular diseases (36.7%) followed by obesity (22%). Overall, 29 patients (4.5%) died or were hospitalized at 1 or 3-month follow-up. Death or hospitalization was positively associated with older ages, with a significant linear trend (OR 3.05; 95% CI 1.16-8.06, for patients aged 80 or more years compared to those aged less than 65). Data on long COVID at 3 months were available for 323 (49.8%) patients. A positive association emerged for females compared to men, with an OR of 2.14 (95% CI 1.30-3.53) for any symptoms. Conversely, inverse associations were found for treatment groups as compared to the control one, with significant estimates among patients treated with antiviral drugs for any symptoms (OR 0.43, 95% CI 0.21-0.87) and patients treated with mAbs for any neuro-behavioral symptoms (OR 0.48, 95% CI 0.25-0.92). CONCLUSIONS: We report beneficial effect of early use of anti-SARS-CoV-2 antivirals and mAbs on long COVID.

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern.

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759.

Characteristics of the population with mild COVID-19 symptoms eligible for early treatment attended in a single center in Northern Italy.

After more than two years from the first COVID-19 detected case in Brescia, Northern Italy, monoclonal antibodies and antiviral therapy aimed at early treatment of mild COVID-19 in patients at risk of progression and of hospitalization has been approved in Italy. Here we report the characteristics of the population eligible for the COVID-19 early treatments at our COVID-19 Early Therapy Unit of the Infectious Diseases Department of the ASST Spedali Civili of Brescia, with the aim to evaluate the characteristics of the foreign and native groups. Up to March the 31st, 2022, a total of 559 patients were referred to our Unit for COVID-19 early treatment, where 7.6% were foreigners, a group significantly younger than natives (p < 0.05). Particular differences are noticed between the native and the foreign population, where people aged > 65 years old were significantly more frequent among italians (39.7% vs 16.3%, p < 0.01), while primary or acquired immunodeficiencies were more frequent in foreigners (55.8% vs 38.9%, p = 0.03). Substantial differences are noted between native and foreign populations, where 14% and 26% (p < 0.05) respectively have never been vaccinated for COVID-19. Overall, 71% of the referred patients received an early treatment for mild COVID-19, with no differences between the two groups. Overall, on day 28 after treatment, 23 (4%) patients had been hospitalized due to COVID-19 related complications and four died (0,7%), no one was foreigner. In conclusion, while the treatment offered for mild COVID-19 appears to be rather uniform between the native and the foreign populations, some differences, especially in preventive vaccination COVID-19, must be taken into account.

Virtual system for early detection of COVID-19 infection "Etaware-CDT-2020 prototype design" (corroborated by rRT-PCR data).

The 2nd phase of COVID-19 infection outbreak experienced worldwide is an attestation to the decline in the efficiency of COVID-19 detection kits available worldwide. rRT-PCR still remains the best confirmatory test for COVID-19 infection. Sadly, most medical professionals are not conversant with the rRT-PCR protocols. Therefore, more easy-to-use alternatives are required as backup, to compensate for these lapses. "Etaware-CDT-2020" is a virtual system designed for early detection of COVID-19 infection. A comparative COVID-19 diagnosis was conducted using Etaware-CDT-2020, corroborated by rRT-PCR-confirmed COVID-19 results obtained from China (Latitude 35.8617oN and Longitude 104.1954oE), which was the epicentre for COVID-19 infection outbreak. A cross-comparison of results showed that there was a positive correlation between the output result from Etaware-CDT-2020 and rRT-PCR diagnosis from Wuhan (r = 0.92) and Hubei (r = 0.97). Furthermore, there was no significant difference between the diagnostic results of "Etaware-CDT-2020" and rRT-PCR, when compared by T-test (P(t = 0) > 0.05) and Pearson's Chi-Square test (0.04 ≥ P ≤ 0.12). Etaware-CDT-2020 is unique and can be used anywhere, anytime and by anyone. It is accessible, affordable, easy to install, simple to understand and user friendly.

Excess Mortality From Suicide During the Early COVID-19 Pandemic Period in Japan: A Time-Series Modeling Before the Pandemic.

BACKGROUND: Suicide amidst the coronavirus disease (COVID-19) pandemic is an important issue. In Japan, the number of suicides in April 2020 decreased by nearly 20% from that in 2019. To assess the impact of an infectious disease pandemic, excess mortality is often discussed. Our main purpose was evaluating excess mortality from suicide in Japan during the early pandemic period. METHODS: We used data on suicides collected by the National Police Agency of Japan until June 2020. We estimated excess mortality during the early pandemic period (March-June 2020) using a time-series model of the number of suicides before the pandemic. A quasi-Poisson model was employed for the estimation. We evaluated excess mortalities by the categories of age and sex, and by prefecture. RESULTS: No significant excess mortality was observed throughout the early pandemic; instead, a downward trend in the number of suicides for both sexes was noted. For males, negative values of excess mortalities below the lower bound of the 95% prediction interval were observed in April and May. All numbers of females during the period were included in the interval, and the excess mortalities in June were positive and higher than those in April and May. In Tokyo, the number of suicides was below the lower bound throughout the period. CONCLUSION: Our results suggest that various changes, such as communication, and social conditions amid the early COVID-19 pandemic induced a decrease in suicides in Japan. However, continuous monitoring is needed to evaluate the long-term effects of the pandemic on suicides.