Assessment of COVID-19 progression on day 5 from symptoms onset

Abstract

Background A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. Methods Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. Results A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66–0.81) for predicting disease progression by day-11. Conclusion An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

Circulating Type I Interferon Levels in the Early Phase of COVID-19 Are Associated With the Development of Respiratory Failure

“…Since the first outbreak of COVID-19, this pandemic has negatively affected the capacity of local and regional healthcare systems worldwide, resulting in the temporal exhaustion of in-hospital medical services ( 2 , 3 ). The necessity of hospitalization due to COVID-19 is largely affected by the presence of respiratory failure, which typically develops several days (at least 3 days) after the onset of the first symptoms ( 4 , 5 ). Therefore, investigating the initial immune response in the early phase of SARS-CoV-2 infection is important because it may be related to the development of respiratory failure.…”

Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy

“…Many clinical parameters, such as age, coexisting diseases, lymphocyte count, D-dimer and lactate dehydrogenase (LDH), have been reported as predictors of COVID-19 progression since the COVID-19 pandemic began. Although prediction models using some of these parameters for the progression of COVID-19 have been well developed, there have been few reports about the rebound of COVID-19 13 14. One retrospective study reported that patients with rebound pneumonia tended to terminate steroids earlier in the disease process and showed a poor prognosis 15.…”

Key Considerations for Phase 2 or 3 Clinical Study Design of Anti-Inflammatory Agent for COVID-19 Treatment

“…Bhaskar, et al reported that anti-inflammatory agents have a mechanism to block hyperinflammatory conditions by targeting cytokine-related signal transduction pathways and have pharmacological properties in which the risk of immunosuppression of anti-inflammatory agents may be greater than the risk of COVID-19 for immunocompromised patients ( Bhaskar et al, 2020 ). In the literature related to the clinical course of COVID-19, Gentilotti et al reported that it usually takes 5–7 days from the onset of symptoms of COVID-19 to hospitalization, which is an inflection point where respiratory symptoms are likely to worsen due to the action of excessive inflammation ( Gentilotti et al, 2021 ).…”

“…For the target population of this study design, we judged that inpatients would be the most appropriate given that it usually takes between 5 and 7 days from symptom onset to hospitalization for COVID-19 which is an inflection point for respiratory symptoms to likely worsen as a function of excessive inflammation ( Gentilotti et al, 2021 ). Considering the timing of the anti-inflammatory treatment and the results of anti-inflammatory agent trials for COVID-19, it seemed appropriate to proceed with clinical trials of anti-inflammatory drugs for COVID-19 for hospitalized patients with severe or a higher severity of COVID-19.…”