LitCovid-sentences  

PMC:7558233 / 26375-40054 JSONTXT 6 Projects

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Id Subject Object Predicate Lexical cue
T151 0-34 Sentence denotes 8 Advances in clinical management
T152 35-172 Sentence denotes Similar to the cases of SARS and MERS infection, no effective therapies with proven efficacy have been developed as yet against COVID-19.
T153 173-342 Sentence denotes Therefore, recommendations for therapeutic intervention (including supportive therapy) have been based on extrapolation of published guidelines or expert consensus [78].
T154 343-448 Sentence denotes Most pharmacological treatments were extrapolated from treatments used during the SARS or MERS outbreaks.
T155 449-550 Sentence denotes The main findings from the clinical trials of COVID-19 in mainland China were summarized in Table 1 .
T156 551-803 Sentence denotes However, at the initial stage of the COVID-19, few clinical trial findings were available to inform clinicians regarding which medications had the greatest efficacy in treating patients with COVID-19 and whether targeted therapies existed for COVID-19.
T157 804-896 Sentence denotes Table 1 Summary of the main findings from the clinical trials of COVID-19 in mainland China.
T158 897-998 Sentence denotes Treatment Target population Reduces viral loads Improvement in clinical outcomes Main adverse effects
T159 999-1180 Sentence denotes Lopinavir–ritonavir Severe COVID-19 Probable No significant acceleration in the time to clinical improvement Gastrointestinal tract symptoms; impairment of liver and kidney function
T160 1181-1183 Sentence denotes 


T161 1184-1356 Sentence denotes Remdesivir Severe COVID-19 Probable No significant acceleration in the time to clinical improvement Gastrointestinal tract symptoms; impairment of liver and kidney function
T162 1357-1359 Sentence denotes 


T163 1360-1513 Sentence denotes Favipiravir Severe COVID-19 Yes Increase the rate of improvement of chest computed tomographic findings Diarrhea; impairment of liver and kidney function
T164 1514-1516 Sentence denotes 


T165 1517-1694 Sentence denotes Chloroquine Moderate-to-severe COVID-19 Yes No significant acceleration in the time to clinical improvement Prolongation of Qt intervals; impairment of liver and kidney function
T166 1695-1697 Sentence denotes 


T167 1698-1822 Sentence denotes Convalescent plasma Critical illness of COVID-19 Yes No significant acceleration in the time to clinical improvement Unknown
T168 1823-1825 Sentence denotes 


T169 1826-1985 Sentence denotes Lianhuaqingwen capsule Moderate COVID-19 No Accelerate symptom improvement and increase the rate of symptom improvement impairment of liver and kidney function
T170 1986-1988 Sentence denotes 


T171 1989-2181 Sentence denotes Granulocyte colony stimulating factor Lymphopenic patients with COVID-19 No Decrease the likelihood of disease progression and increase the rate of symptom improvement Leukocytosis; osteodynia
T172 2182-2184 Sentence denotes 


T173 2185-2312 Sentence denotes Hydrogen oxygen mixed gas inhalation Symptomatic patients with COVID-19 Unknown Rapidly ameliorate respiratory symptoms Unknown
T174 2313-2540 Sentence denotes The fact that viral infection (including viral sepsis) [79] remains the key driver of the pathogenesis of COVID-19 has fueled research exploring the efficacy of antiviral medications in patients with severe or critical illness.
T175 2541-2846 Sentence denotes Taking into account the findings from in vitro [80], [81] and in vivo studies [82], [83], [84], lopinavir/ritonavir, remdesivir, and chloroquine (previously intended for the treatment of Ebola virus or human immunodeficiency virus (HIV) infections) have been repurposed for combating SARS-CoV-2 infection.
T176 2847-3093 Sentence denotes In a randomized clinical trial conducted in the early stage of the epidemic in China, patients with severe COVID-19 were assigned to receive standard-of-care alone or in combination with a 14-day course of treatment with lopinavir/ritonavir [82].
T177 3094-3254 Sentence denotes Neither the duration from randomization to clinical improvement nor the mortality rate differed significantly between the treatment group and the control group.
T178 3255-3446 Sentence denotes Subsequently, in another double-blinded clinical trial, patients with severe COVID-19 were randomly allocated to receive standard-of-care alone or in combination with 10 d of remdesivir [81].
T179 3447-3571 Sentence denotes Again, there was no significant difference in the time to clinical improvement, which was the primary endpoint of the study.
T180 3572-3696 Sentence denotes Neither lopinavir/ritonavir nor remdesivir markedly reduced viral loads, as monitored dynamically throughout the two trials.
T181 3697-3762 Sentence denotes Several reasons could have accounted for these negative findings.
T182 3763-3950 Sentence denotes It was notable that patients entered the clinical trials after a median duration of 11–13 d, which could have diminished the efficacy as compared with earlier administration of the drugs.
T183 3951-4100 Sentence denotes In fact, early administration of lopinavir/ritonavir (within 10 d of symptom onset) has been associated with a shorter course of viral shedding [83].
T184 4101-4387 Sentence denotes Moreover, both of these trials might have been underpowered for statistical analysis due to the emergency of the outbreak and the premature cessation of patient recruitment (there was difficulty in recruiting sufficient patients once the epidemiologic curve has flattened within Wuhan).
T185 4388-4506 Sentence denotes Nevertheless, the results did not preclude the use of lopinavir/ritonavir and remdesivir for severe cases of COVID-19.
T186 4507-4823 Sentence denotes Both trials indicated a numerically faster time to clinical improvement in the treatment group [82], [85] and, in a more recent clinical trial, administration of remdesivir for 10 d was associated with a faster time to clinical improvement and a lower mortality rate by 14 d, as compared with the placebo group [86].
T187 4824-5011 Sentence denotes Furthermore, when administered in combination with IFN-β and ribavirin, lopinavir/ritonavir has been associated with a marked reduction in viral loads compared with usual care alone [87].
T188 5012-5130 Sentence denotes Therefore, combined antiviral medications might have a role in accelerating viral clearance in patients with COVID-19.
T189 5131-5223 Sentence denotes Several other candidate medications have also been tested in clinical settings for COVID-19.
T190 5224-5320 Sentence denotes The effects of chloroquine and hydroxychloroquine on patients with COVID-19 remain under debate.
T191 5321-5632 Sentence denotes While chloroquine effectively reduced viral loads and achieved negative conversion of viral assays in hospitalized patients [88], the administration of hydroxychloroquine failed to increase the probability of achieving negative conversion of viral assays by 28 d in patients with mild-to-moderate COVID-19 [84].
T192 5633-5876 Sentence denotes In a pilot open-label study, favipiravir was shown to markedly shorten the time to viral clearance and increase the rate of improvement in chest imaging compared with a combination treatment with lopinavir/ritonavir plus IFN-α inhalation [89].
T193 5877-5981 Sentence denotes This finding added to the scientific evidence on candidate medications with potent antiviral activities.
T194 5982-6164 Sentence denotes Apart from heightened inflammatory response and viral infections, the aberrant immune response has been the canonical pathophysiological change leading to the poor clinical outcomes.
T195 6165-6302 Sentence denotes Lymphopenia was identified in up to 80% of patients with COVID-19 and was significantly correlated with the risk of mortality [39], [90].
T196 6303-6538 Sentence denotes Mobilizing the trafficking of lymphocytes to the peripheral blood with recombinant human granulocyte colony stimulating factor (rhG-CSF) might represent an appealing therapeutic approach for patients with COVID-19 who have lymphopenia.
T197 6539-6914 Sentence denotes A recent randomized clinical trial revealed that, despite the failure to accelerate clinical improvement, rhG-CSF markedly increased CD8+ T cell and natural killer (NK) cell count while reducing the risk of progression to critical illness or death compared with the usual care alone [91], particularly in patients with a blood lymphocyte count below 400 per cubic milliliter.
T198 6915-7014 Sentence denotes Mechanistic studies unraveling the mode of actions of rhG-CSF in patients with COVID-19 are needed.
T199 7015-7194 Sentence denotes Corticosteroids confer powerful anti-inflammatory effects and hence may ameliorate inflammation-mediated lung injury, thus preventing progression to respiratory failure and death.
T200 7195-7404 Sentence denotes In an observational study, the use of methylprednisolone was found to be associated with a markedly lower risk of mortality in patients with COVID-19 who had developed acute respiratory distress syndrome [92].
T201 7405-7822 Sentence denotes In an echo of these findings, a recent clinical trial recruiting hospitalized patients with COVID-19 showed that the oral or intravenous administration of dexamethasone (6 mg·d–1) for up to 10 d resulted in a markedly lower 28-day mortality in comparison with the control group among patients receiving invasive mechanical ventilation at randomization or receiving oxygen without invasive mechanical ventilation [93].
T202 7823-7972 Sentence denotes The benefit was also clear in patients who were being treated more than 7 d after symptom onset, when inflammatory lung damage became more prominent.
T203 7973-8142 Sentence denotes However, no significant effects were observed among patients not receiving any respiratory support, which was in line with the findings from a recent meta-analysis [94].
T204 8143-8226 Sentence denotes Targeted therapy has been very limited among critically ill patients with COVID-19.
T205 8227-8396 Sentence denotes By extrapolating from experience in managing patients with SARS and MERS, efforts have been made to treat critically ill patients with COVID-19 with convalescent plasma.
T206 8397-8559 Sentence denotes In a pilot single-arm study with five patients, convalescent plasma with high-titers neutralizing antibodies appeared to improve the overall clinical status [95].
T207 8560-8744 Sentence denotes On the basis of usual care in a randomized clinical trial, convalescent plasma therapy did not confer additional benefits in terms of the time to clinical improvement within 28 d [69].
T208 8745-9094 Sentence denotes However, convalescent plasma did show clinical benefits in the subgroup of severe patients, albeit not in critically ill patients. [96] Nevertheless, the bona fide therapeutic benefits of convalescent plasma cannot be precluded, as the trial was underpowered for analysis due to the difficulty in recruiting patients at later stages of the outbreak.
T209 9095-9301 Sentence denotes Although there was no statistically significant difference, a possible clinical benefit was observed for patients with severe COVID-19 but not for patient subgroups with a life-threatening level of illness.
T210 9302-9419 Sentence denotes Several studies in China have observed disseminated intravascular coagulation (DIC) in most non-survivors [97], [98].
T211 9420-9603 Sentence denotes Significantly higher levels of D-dimer and fibrin degradation products, as well as a longer prothrombin time, suggested that coagulopathy might be associated with poor prognosis [99].
T212 9604-9700 Sentence denotes The dynamic changes in D-dimer levels correlated positively with the prognosis of COVID-19 [98].
T213 9701-9949 Sentence denotes Patients with a sepsis-induced coagulopathy score greater than or equal to 4, or a D-dimer level greater than six times the upper limit of normal, exhibited a lower mortality rate when receiving low molecular weight heparin for 7 d or longer [100].
T214 9950-10167 Sentence denotes When given anticoagulant treatment, attention should be paid to avoid the development of diffuse alveolar hemorrhage, which is a life-threatening complication that may occur after the administration of warfarin [101].
T215 10168-10259 Sentence denotes Non-pharmacological interventions might have a role in the clinical management of COVID-19.
T216 10260-10384 Sentence denotes Patients with COVID-19 have been characterized by increasingly laborious breathing as a result of greater airway resistance.
T217 10385-10572 Sentence denotes Due to smaller molecular weight, helium–oxygen mixed gas has been applied to ameliorate dyspnea in patients with respiratory failure [102] and chronic obstructive pulmonary disease [103].
T218 10573-10701 Sentence denotes However, due to the low cost-effectiveness ratio, helium–oxygen mixed gas has not been extensively adopted in clinical practice.
T219 10702-10890 Sentence denotes In contrast, hydrogen/oxygen mixed gas (H2–O2) could be generated via the direct electrolysis of water with the use of a commercialized instrument, and could be adopted for home use [104].
T220 10891-11010 Sentence denotes H2–O2 inhalation has recently been shown to markedly ameliorate dyspnea in patients with central airway stenosis [104].
T221 11011-11148 Sentence denotes It is essential to determine whether H2–O2 inhalation would result in a major clinical improvement in symptomatic patients with COVID-19.
T222 11149-11457 Sentence denotes In an open-label multicenter clinical trial, H2–O2 inhalation led to a marked and rapid amelioration of the key respiratory symptoms (including dyspnea, chest pain, and cough scale) and improved the resting oxygen saturation and disease severity in patients with COVID-19 who had dyspnea at enrollment [105].
T223 11458-11685 Sentence denotes Based on these findings, H2–O2 inhalation has been endorsed by the National Health Commission of the People’s Republic of China for COVID-19 patients with dyspnea or those in facilities without sufficient oxygen supplies [106].
T224 11686-11767 Sentence denotes Traditional Chinese medicine has been a treasure trove of complementary medicine.
T225 11768-11885 Sentence denotes Efforts have been made to explore the effects of a panel of herbal formulas for the management of SARS and influenza.
T226 11886-12001 Sentence denotes For example, Lianhuaqingwen (LH) capsule has been approved for the treatment of mild-to-moderate SARS [107], [108].
T227 12002-12226 Sentence denotes Therefore, priority could be given to the development of LH capsules, because off label marketing medications would help reduce the time for research and development (R&D) against other candidate medications in the pipeline.
T228 12227-12318 Sentence denotes In an in vitro study, LH capsule yielded potent antiviral effects against SARS-CoV-2 [109].
T229 12319-12495 Sentence denotes Based on these observations, a multicenter randomized clinical trial was undertaken to determine the effectiveness of LH capsule plus usual care, versus usual care alone [110].
T230 12496-12732 Sentence denotes At Day 14, treatment with LH capsule was associated with a significantly higher rate of symptom recovery and a markedly shortened time to symptom recovery, although no differences in the viral loads were observed between the two groups.
T231 12733-12982 Sentence denotes It is notable that these therapeutic effects might not be related to the antiviral effects because the serum concentrations of LH capsule were markedly lower than those reported in the in vitro study in which the antiviral effects were potent [109].
T232 12983-13143 Sentence denotes LH capsules also exhibited anti-inflammatory and anti-oxidative effects via suppressing cytokine release, according to the results from an in vitro study [110].
T233 13144-13328 Sentence denotes These findings have resulted in the endorsement of LH capsules by the National Health Commission of the People’s Republic of China for the treatment of mild-to-moderate COVID-19 [106].
T234 13329-13505 Sentence denotes Apart from LH capsules, other candidate herbal formulas such as Xuebijing injection and Liu Shen capsule have demonstrated antiviral activities against SARS-CoV-2 [111], [112].
T235 13506-13679 Sentence denotes Multicenter clinical trials to determine the efficacy of these herbal formulas (i.e., Xuebijing injection for severe or critically ill cases with COVID-19) are now underway.