Slower Recovery with Early Lopinavir/Ritonavir use in Pediatric COVID-19 Patients: A Retrospective Observational Study.

OBJECTIVES: There was initially insufficient understanding regarding suitable pharmacological treatment for pediatric Coronavirus Disease 2019 (COVID-19) patients. Lopinavir-ritonavir (LPV/r) was originally used for the treatment of Human Immunodeficiency Virus-1 (HIV-1) infection. It was also used in patients with severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) with positive results. Nonetheless, results from recent randomized controlled trials and observational studies on COVID-19 patients were unfavorable. We sought to evaluate the clinical outcomes associated with early treatment with LPV/r for pediatric COVID-19 patients. STUDY DESIGN: A total of 933 COVID-19 patients aged ≤ 18 years were admitted between 21 January 2020 and 31 January 2021 in Hong Kong. Exposure was receiving LPV/r within the first two days of admission. Time to clinical improvement, hospital discharge, seroconversion and hyperinflammatory syndrome, cumulative costs, and hospital length of stay were assessed. Multivariable Cox proportional hazard and linear models were performed to estimate hazard ratios (HR) and their 95% confidence intervals (CI) of time-to-event and continuous outcomes, respectively. RESULTS: LPV/r users were associated with longer time to clinical improvement (HR 0.51, 95% CI 0.38-0.70; p < 0.001), hospital discharge (HR 0.51, 95% CI 0.38-0.70; p < 0.001) and seroconversion (HR 0.59, 95% CI 0.43-0.80; p < 0.001) when compared with controls. LPV/r users were also associated with prolonged hospital length of stay (6.99 days, 95% CI 6.23-7.76; p < 0.001) and higher costs at 30 days (US$11,709 vs US$8270; p < 0.001) as opposed to controls. CONCLUSION: Early treatment with LPV/r for pediatric COVID-19 patients was associated with longer time to clinical improvement. Our study advocates the recommendation against LPV/r use for pediatric patients across age groups.

Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort.

Aim: This study was conducted in order to evaluate the association between metformin use and clinical outcomes in type 2 diabetes mellitus (T2DM) patients hospitalized with coronavirus disease 2019 (COVID-19). Methods: Patients with T2DM with confirmed diagnosis of COVID-19 and admitted between January 21, 2020, and January 31, 2021 in Hong Kong were identified in our cohort. Exposure was defined as metformin use within 90 days prior to admission until hospital discharge for COVID-19. Primary outcome was defined as clinical improvement of ≥1 point on the WHO Clinical Progression Scale (CPS). Other outcomes were hospital discharge, recovery, in-hospital death, acidosis, hyperinflammatory syndrome, length of hospitalization, and changes in WHO CPS score. Results: Metformin use was associated with greater odds of clinical improvement (OR = 2.74, p = 0.009), hospital discharge (OR = 2.26, p = 0.009), and recovery (OR = 2.54, p = 0.005), in addition to lower odds of hyperinflammatory syndrome (OR = 0.71, p = 0.021) and death (OR = 0.41, p = 0.010) than control. Patients on metformin treatment had a shorter hospital stay (-2.76 days, p = 0.017) than their control counterparts. The average WHO CPS scores were significantly lower in metformin users than non-users since day 15 (p < 0.001). However, metformin use was associated with higher odds of acidosis. Conclusions: Metformin use was associated with lower mortality and lower odds for hyperinflammatory syndrome. This provides additional insights into the potential mechanisms of the benefits of metformin use in T2DM patients with COVID-19.

Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: Propensity score analysis of a territory-wide cohort in Hong Kong.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) patients with Coronavirus Disease 2019 (COVID-19) have poorer prognosis. Inconclusive evidence suggested dipeptidyl peptidase-4 inhibitors (DPP4i) might reduce inflammation and prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry, hence further evaluation on DPP4i is needed. METHODS: 1214 Patients with T2DM were admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong. Exposure was DPP4i use within the 90 days prior to admission for COVID-19. Assessed outcomes included clinical deterioration, clinical improvement, low viral load, positive Immunoglobulin G (IgG) antibody, hyperinflammatory syndrome, proportion of IgG antibody, clinical status and length of hospitalization. Multivariable logistic and linear regression models were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes and continuous outcomes, respectively. RESULTS: DPP4i users (N = 107) was associated with lower odds of clinical deterioration (OR=0.71, 95%CI 0.54 to 0.93, P = 0.013), hyperinflammatory syndrome (OR=0.56, 95%CI 0.45 to 0.69, P < 0.001), invasive mechanical ventilation (OR=0.30, 95%CI 0.21 to 0.42, P < 0.001), reduced length of hospitalization (-4.82 days, 95%CI -6.80 to -2.84, P < 0.001), proportion of positive IgG antibody on day-3 (13% vs 8%, p = 0.007) and day-7 (41% vs 26%, P < 0.001), despite lack of association between DPP4i use and in-hospital mortality. CONCLUSION: DPP4i use was associated with reduced odds of clinical deterioration and hyperinflammatory syndrome. Prospective studies are warranted to elucidate the role of DPP4i in T2DM and COVID-19.

Handling 22NaCl by the blood-brain barrier and kidney: its relevance to salt-induced hypertension in dahl rats.

We previously reported that inappropriate renal vasoconstriction in Dahl salt-sensitive (DS) rats fed high NaCl diets may cause sodium retention. The present study examined the distribution and elimination of 22Na in DS and Dahl salt-resistant (DR) rats, and we determined whether an abnormality in renal function might also cause sodium retention in DS rats. Following an intravenous bolus of 4 microCi 22NaCl in prehypertensive DS and DR rats with similar blood pressures on low (0.23%) or high (8% for 4 days) NaCl diets, urinary clearance of 22Na in 1 hour was about 4 times less in DS than DR rats, and renal retention of 22Na was up to 8 times greater in DS than DR rats (P<0.01), suggesting that a renal functional defect may contribute to salt retention in DS rats; however, its uptake in tail artery, heart, lungs, liver, and spleen was similar in DS and DR rats. Uptake in brain was up to 5 times greater in DS than DR rats (P<0.01). Cerebrospinal fluid 22Na radioactivity (in counts per minute) revealed that the blood-brain barrier is 5 to 8 times more permeable to sodium in DS than DR rats (P<0.01). Cerebrospinal fluid volume and brain water content increased significantly (P<0.01) in DS but not DR rats on an 8% NaCl diet. Intracerebroventricular bolus injection of 0.06 mL of 4.5 mol/L NaCl acutely and transiently induced the same degree of hypertension in DR and DS rats, whereas similar volume injections of isotonic saline, 4.5 mol/L Na-acetate, or 4.5 mol/L NaBr did not produce hypertension in either strain. We conclude that functional abnormalities in DS rat kidneys may cause retention of NaCl and that an increased blood-brain barrier permeability to NaCl may enhance its access to sites in the brain that are then activated and induce hypertension.

Low-dose CT of the lungs: preliminary observations.

The potential of low-dose computed tomography (CT) of the lungs was critically evaluated in two patients with normal-appearing lungs and 10 patients with a wide diversity of underlying parenchymal abnormalities. At each of five levels, in addition to routine scans obtained at 120 kVp and 140 mA, a scan at 10 mA and a half scan at 10 mA were obtained, with all other parameters held constant. Each scan was evaluated visually to assess anatomic clarity as well as the presence of artifacts and the extent of graininess. At all levels of the thorax, visualization of parenchymal structures was not affected by decreasing the milliamperage. It appears that high-quality, diagnostic images of the lung can be obtained with a very low radiation dose. Although further evaluation is necessary, the potential of low-dose CT for use in the pediatric population in particular, as well as for screening in patients at high risk for developing lung cancer, is apparent.

Bone mineralization in the distal forearm of hemiplegic patients.

Bone mineral content was measured by single photon absorptiometry using a modified bone densitometer (Packard) with 125I as the source. In 42 hemiplegic subjects, matched for sex and age, the bone density was compared bilaterally on the radius and ulna 2 cm and 4 cm above the wrist. The nonparalyzed side served as a control for the paralyzed side. The results indicate a consistent, general loss of bone mineral on the paralyzed side compared with the nonparalyzed side. The extent of demineralization in females was greater than in male subjects. Right-dominant left-paralyzed patients showed a greater loss of bone density than right-dominant right-paralyzed subjects. The absorption ratio of the paralyzed vs the nonparalyzed sides revealed that there was a 5.3% and 7.4% decrease in the average bone density at 4 and 2 cm above the wrist, respectively. There was a progressive loss of bone mineral content relative to time after the onset of paralysis, amounting to an average of 6.4% approximately three months after the onset of injury. It was estimated that before the onset of paralysis there was an excess of bone mineral on the dominant vs the nondominant side of +5.4% and +3.2% for males and females, respectively.