Moderate COVID-19: Clinical Trajectories and Predictors of Progression and Outcomes.

BACKGROUND: Patients with COVID-19 commonly present at healthcare facilities with moderate disease, i.e., pneumonia without a need for oxygen therapy. AIM: To identify clinical/laboratory characteristics of patients with moderate COVID-19, which could predict disease progression. METHODS: 384 adult patients presented with moderate COVID-19 and admitted to two hospitals were retrospectively evaluated. In a multivariate analysis gender, age, BMI, Charlson Comorbidity Index (CCI) and National Early Weaning Score 2 were treated as co-variates. The development of hypoxemic respiratory failure, intubation rate and risk of death were considered as dependent variables. Estimated values are presented as odds-ratio (OR) with 95% confidence interval (CI). RESULTS: Most of the patients were male (63.28%) with a mean (standard deviation) age of 59 (16.04) years. Median (interquartile range) CCI was 2 (1-4). A total of 58.85% of the patients developed respiratory failure; 6.51% were intubated, and 8.85% died. The extent of pneumonia in chest X-ray (involvement of all four quartiles) [OR 3.96 (1.18-13.27), p = 0.026], respiratory rate [OR 1.17 (1.05-1.3), p = 0.004], SatO2 [OR 0.72 (0.58-0.88), p = 0.002], systolic blood pressure [OR 1.02 (1-1.04), p = 0.041] and lymphocyte count [OR 0.9993 (0.9986-0.9999), p = 0.026] at presentation were associated with the development of respiratory failure. The extent of pneumonia [OR 26.49 (1.81-387.18), p = 0.017] was associated with intubation risk. Age [OR 1.14 (1.03-1.26), p = 0.014] and the extent of pneumonia [OR 22.47 (1.59-316.97), p = 0.021] were associated with increased risk of death. CONCLUSION: Older age, the extent of pneumonia, tachypnea, lower SatO2, higher systolic blood pressure and lymphopenia are associated with dismal outcomes in patients presenting with moderate COVID-19.

Pharmacological Treatment of Patients with Mild to Moderate COVID-19: A Comprehensive Review.

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.

A Controllable Inflammatory Response and Temporary Abnormal Coagulation in Moderate Disease of COVID-19 in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is now a worldwide challenge for public health. Among 7 million patients, about 80% present mild to moderate disease, but studies dedicate to these patients are actually scarce. The aim of our study is to clarify the characteristics of laboratory test index of COVID-19 patient with moderate symptoms during the first wave of the pandemic in Wuhan, China. METHODS: In this retrospective cohort study, we included 107 adult inpatients with confirmed moderate disease of COVID-19 from the Affiliated Hospital of Jianghan University during February and early March 2020. All of these patients were recovered from COVID-19 and discharged from hospital. Demographic, clinical, and laboratory data of admission and discharge were extracted from electronic medical records and analyzed using SPSS, as well as among young, middle age and elderly people. RESULTS: The median age of this cohort of patients was 56.0 years. And the median hospitalization time was 16 days. Common clinical manifestations included fever, cough, asthenia and shortness of breath. On admission, laboratory results showed normal or increased neutrophil ratio, low lymphocyte count, decreased hemoglobin level, and increased inflammatory indicators (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)); and some patients were complicated with coagulation disorder and myocardial damage. Furthermore, patients older than 60 years had statistically higher CRP, ESR and fibrinogen level. As the health condition was improved at discharge, the median level of most laboratory results were in the normal range except hemoglobin and related blood cell count, as well as inflammatory indicator ESR. And patients older than 60 years showed slower recovery on coagulation parameters when compared to younger patients. CONCLUSIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a controllable inflammatory response in moderate disease of COVID-19 in Wuhan, China. Since patients older than 60 years had higher inflammatory state and more dysregulated coagulation condition, it might be essential to closely assess their illness.

Test and treat COVID 65 plus - Hydroxychloroquine versus placebo in early ambulatory diagnosis and treatment of older patients with COVID19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this trial is to identify the effect of ambulatory treatment in early COVID-19 disease with hydroxychloroquine on the rate of hospitalization or death in older patients above the age of 64. TRIAL DESIGN: Parallel, 2:1 randomization, double blind, placebo-controlled, multi-center trial. PARTICIPANTS: Male and female patients above the age of 64 (i.e. ≥65 years of age) with COVID-19 diagnosis confirmed by SARS-CoV2 positive throat swab (PCR). Patients can only be included within 3 days of symptom onset in ambulatory care if they consent to the study procedure and are able to adhere to the study visit schedule and protocol requirements (including telephone visits concerning symptoms and side effects). Severity of disease at inclusion is mild to moderate defined as not requiring hospital admission: SpO2 >94%, respiratory rate <20, mental state alert, no signs of septic shock. Cardiac risk is minimised by requiring a Tisdale score ≤ 6. Patients are recruited in the two german cities of Ulm and Tübingen in various ambulatory care settings. INTERVENTION AND COMPARATOR: Each patient will be given a first dose of 600 mg Hydroxychloroquine or the equivalent number of placebo capsules (3 capsules) at the day of inclusion. From the 2nd day on, each patient will get 200 mg or the equivalent number of placebo capsules twice a day (400mg/day) until day 7 (6 more does of 400 mg); a cumulative dose of 3 g. MAIN OUTCOMES: Rate of hospitalization or death at day 7 after study inclusion RANDOMISATION: All consenting adult patients having confirmed COVID-19 are randomly and blindly allocated in a 2:1 ratio to either IMP or placebo. The biostatistical center produced a randomization list (block randomization) with varying block length and stratified for the study center. This list is provided for packaging to the pharmaceutical unit which is providing encapsulated placebo and IMP. Only the pharmaceutical unit is aware of group allocation according to the randomization list. BLINDING (MASKING): Patients and investigators, as well as treating physicians are blinded to the treatment- allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the first stage of an adaptive design 120 patients in a 2:1 ration: 72 Verum and 36 Placebo, plus an increase for 10% drop outs. After interim analysis, the total sample size will be calculated based on the effect seen in the first stage. Total sample size is estimated approximately n = 300-400 patients. TRIAL STATUS: Protocol version number: V3, 19.05.2020 Recruitment not yet started but is anticipated to begin by June 2020 and be complete by December 2020 TRIAL REGISTRATION: ClinicalTrials.gov: NCT04351516 , date: 17 April 2020 EudraCT: 2020-001482-37, date: 30 March 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.