The effects of altered PK/PD parameters on efficacy and toxicity of therapeutic drugs in critically ill patients with COVID-19 (preprint)

Although many therapies have been proposed, there is no evidence of any effective treatment for COVID-19 to date. Currently, the main therapies being used to treat the critically patients with COVID-19 are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. Pharmacokinetics (PK) and pharmacodynamics (PD) play an important role in different clinical situations, and are keys to balance the effect (reduction of SARS-CoV-2 virus and symptom improvement) and toxicity (adverse effects). Critically ill patients always have altered PK and PD due to multiple factors such as hypoproteinemia, organ dysfunction, and organ support treatment including continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO). Here we provide an overview of the effects of the clinical treatments for critically COVID-19 patients and the pathological state of patients on pharmacokinetics and pharmacodynamics parameters of therapeutic drugs in detail. However, current evidence is insufficient to speculate the changes of drug concentration of antimicrobials, therapeutic drug monitoring (TDM) is a useful tool used in severe patients since many suspected factors were exist to influence the clinical responses and adverse drug reactions of drugs.

Hypoproteinemia predicts disease severity and mortality in COVID-19: a call for action.

Proteins represent the major building blocks of body tissues, and they regulate signaling involved in most cellular activities. Coronavirus disease 2019 (COVID-19) infection has been associated with high fatality, especially among older adults. The main cause of death is pulmonary tissue damage and multiple organ failure. The disease is associated with a hypercatabolic state that entails excessive protein loss. This review commentary sheds the light on hypoproteinemia in symptomatic/hospitalized COVID-19 with a special emphasis on its pathophysiology, screening, as well as its contribution to disease severity and adverse effects.

Risk Factors of Secondary Infections in Severe and Critical Patients Hospitalized with COVID-19: A Case-Control Study (preprint)

Background: Severe patients hospitalized with COVID-19 suffered secondary infections which greatly increased the length of hospital stay and the mortality. We aimed to explore risk factors of secondary infections that can help clinicians early implement preventive measures to dispose of severe and critical inpatients with COVID-19.Methods: A case-control study enrolled 238 severe and critical patients with COVID-19. Characteristics of cases and controls were compared.Results: Severity of illness on admission, ICU admission, ventilator, central venous catheterization were common in the cases, however almost none of these factors was observed in the controls. Multivariable regression showed risk factors of secondary infections included male (OR 4.08; 95% CI 1.58-10.50), age 65 or older (OR 3.11; 95% CI 1.25-7.76), heart diseases (OR 3.96; 95% CI 1.40-11.27), hypoproteinemia on admission (OR 6.41; 95% CI 1.65-24.92) and corticosteroids (OR 19.83; 95% CI 7.3-53.55) and proton-pump inhibitors (OR 3.96; 95% CI 1.51-10.37).Conclusions: male, older age, heart diseases, hypoproteinemia, corticosteroid and proton-pump inhibitors were independent risk factors of secondary infections. Inpatients needing ICU admission and invasive devices still need to be given optimal cares and to be minimized the duration.

Analysis of factors affecting the prognosis of COVID-19 patients and viral shedding duration.

The clinical characteristics of patients with COVID-19 were analysed to determine the factors influencing the prognosis and virus shedding time to facilitate early detection of disease progression. Logistic regression analysis was used to explore the relationships among prognosis, clinical characteristics and laboratory indexes. The predictive value of this model was assessed with receiver operating characteristic curve analysis, calibration and internal validation. The viral shedding duration was calculated using the Kaplan-Meier method, and the prognostic factors were analysed by univariate log-rank analysis and the Cox proportional hazards model. A retrospective study was carried out with patients with COVID-19 in Tianjin, China. A total of 185 patients were included, 27 (14.59%) of whom were severely ill at the time of discharge and three (1.6%) of whom died. Our findings demonstrate that patients with an advanced age, diabetes, a low PaO2/FiO2 value and delayed treatment should be carefully monitored for disease progression to reduce the incidence of severe disease. Hypoproteinaemia and the fever duration warrant special attention. Timely interventions in symptomatic patients and a time from symptom onset to treatment <4 days can shorten the duration of viral shedding.

Key to successful treatment of COVID-19: accurate identification of severe risks and early intervention of disease progression (preprint)

Abstract Background COVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference. Methods We analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020,included laboratory examination results, imaging findings, treatment effect, prognosis , etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients. Results 1.Hypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients.The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression. 2.Characteristic images of lung CT had a clear change in COVID - 19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease. 3.Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2 . 4. According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients. Conclusions: 1.Accurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2.Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.

Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China (preprint)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods: A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results: A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. Conclusions Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

Characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan, China (preprint)

BackgroundSince Dec 2019, SARS-CoV-2 has caused about fifty thousand patients and over two thousand deaths in Wuhan, China. We reported characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan. MethodsData of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, were retrospectively collected from electronic medical records. Characteristics were compared between patients who died or recovered, and between patients with different disease severity. ResultsBy Feb 25, 2020, 403 patients were enrolled, 100 died and 303 recovered. Most of non-survivors tended to be males, old aged, or with chronic diseases. Duration from illness onset to admission was 9 (7-12) days. Patients with severe or critical illness had more days from onset to admission compared to those with ordinary illness. Lymphopenia, anemia, hypoproteinemia, and abnormal serum sodium were presented in 52.6%, 54.6%, 69.8%, and 21.8% cases, respectively. Patients who died or with severe/critical illness showed increased white blood cell and neutrophil count, serum total bilirubin, creatinine, hypersensitive troponin I, D-dimer, procalcitonin, and C-reactive protein, and decreased red blood cell, lymphocyte, platelet count, and serum albumin on admission compared to those who recovered or with ordinary illness. Complications of acute organ injury and secondary infection were common in patients with COVID-19, especially in non-survivors. ConclusionsMultiple homeostasis disturbances were common in patients with severe or critical illness at admission. Early support should be provided, especially for old men with chronic disease, which is vital to control disease progression and reduce mortality of COVID-19 during epidemic ongoing outbreak.