New study: Krezhi and Abdolge's new crown has had little effect

outbreak of new coronary pneumonia (COVID-19), scientists have launched several studies to explore the effectiveness of existing treatments. On March 23, local time, the pharmaceutical preprinted platform medRxiv published a study online (without peer review) that showed that, based on the results of randomized controlled trials in 44 patients, the treatment of Lopinewe/Litonavi (Klic) or Abidor monotherapy had little effect in the clinical treatment of mild moderate COVID-19. In addition, The Lopinave/Litonave treatment may lead to adverse reactions in more patients.
The authors of the study are all from the Eighth People's Hospital of Guangzhou, affiliated with Guangzhou Medical University, and the authors are Li Linghua and Zhang Fuchun of the Infection Department of the Eighth People's Hospital of Guangzhou, and Deng Xilong, director of the Hospital's Intensive Medicine Department. It is reported that the Eighth People's Hospital of Guangzhou is a designated hospital for the treatment of COVID-19 patients, and has treated more than 80% of the confirmed COVID-19 patients in Guangzhou.
the study (NCT04252885), known as ELACOI, is a single-center randomized controlled study to explore the efficacy and safety of Lopinavi/Litonavi (LPV/r) or Arbidol monodols for the treatment of mild or moderate COVID-19 patients.
, we don't yet know the actual clinical effects of LPV/r or Abidor on the new coronavirus disease, the authors said. Therefore, we urgently need a randomized clinical trial (RCT) to assess their efficacy or adverse consequences.
The study had planned to recruit 125 COVID-19 patients, but because the outbreak was under control, the number of new diagnoses in Guangzhou was small, and the "recruitment pool" for drug trials quickly ran out, eventually including only 44 patients. Of these, 21 were randomly assigned to receive LPV/r, 16 used abidor and 7 did not use antiviral drugs as a control group.
From the baseline characteristics of the three groups, the mid-time time of SARS-CoV-2 nucleic acid test results in the LPV/r group was 8.5 days, the Abidor group was 7 days, and the control group was 4 days.
, more patients treated with LPV/r developed from mild to moderate conditions to severe/critical conditions than in the other two groups.
there was no significant difference in the conversion rate between the 7th and 14th days in the third group, and there was no statistical difference in the rate of fever re-fever, cough remission, chest CT improvement, and deterioration rate of the patient's clinical condition between the three groups.
, 5 patients (23.8%) in the LPV/r group had adverse reactions during the study period. There were no significant adverse events in Abidor or the control group.
also point out that the findings will need to be further validated in the future because the study is limited by a small sample size.new coronary pneumonia is still not a special drug, and one antiviral candidate is the HIV protease inhibitor, the Lopinavir/ritonavir (LPV/r) combination, which is called Krych.
has an effect on the main protease (3CL protease) of sars (Severe Acute Respiratory Syndrome) coronavirus, and has some antiviral activity on the new coronavirus. Lopinave is usually used in lytonave to inhibit the cytochrome P450 to increase the half-life of Lopinave. Both were combined with immunomodulator interferon β-1b, a combination that has been used in clinical trials to treat Middle East Respiratory Syndrome (MERS), and LPV/r has been shown to be effective against HIV-1 over the past decade, with limited side effects.
, the Lopinewe/Litonave combination is widely accessable and large-scale productive. But in a recent paper in the New England Journal of Medicine, teams from China-Japan Friendship Hospital, the National Respiratory Clinical Research Center, and Wuhan Jinyintan Hospital reported the results of clinical trials used to treat COVID-19. Unfortunately, in severe patients, the study failed to observe the effectiveness of the lopinave-litonave treatment compared to conventional treatment.
and Arbidol is a hemocoagulant inhibitor that effectively prevents influenza viruses from fusing with host cells. At the same time, it can induce the body to produce endotopic interferons that resist viral replication, enhance the phagocytorapy function of macrophages, and activate natural killer immune cells.
has been reported to be effective against all types of influenza viruses (A, B, C), especially influenza A viruses (H1N1, H2N2, H3N3) with fewer side effects. Studies have also shown that in cultured cells, Abidor has some direct antiviral effects on reducing the reproduction of SARS virus in cells.
it is worth noting that on February 4, the Chinese Academy of Engineering
, the National Health and Wellness Commission high-level expert group member Li Lanxuan team in Wuhan announced the latest research results of the treatment of new coronary pneumonia, said Abidor can effectively suppress the coronavirus.
Li Lanxuan said that according to preliminary tests, in-body cell experiments showed that Abidor at 10 to 30 micromolar concentrations, compared with the drug-unprocessed control group, can effectively inhibit the coronavirus up to 60 times, and significantly inhibit the virus on the cell lesions effect. researchers assigned each eligible participant to a random number that assigned him or her to a treatment group, which was generated by a computer. Recruited patients were assigned (2:2:1) to three groups.
from February 1 to February 18, 2020, the researchers screened 63 patients with mild to moderate COVID-19, 44 of whom (average age 49.4 years) were successfully included in the study, including 21 men and 23 women.
in Group A (LPV/r), 21 patients were given lopinave (200mg) daily, while oral litonave (50mg) was used as a strengthening.
16 patients in Group B (Abedore group) who received a single dose of Abedore (100 mg, oral). Seven patients in group C (control group) did not receive antiviral medication.
researchers followed all three groups for up to 21 days and collected data on important dates, including fever, hospitalization, neo-coronavirus nucleic acid testing from positive to negative, complications (hypertension, diabetes, etc.), clinical parameters (body temperature, etc.) pulse, breathing rate, oxygen saturation, etc.; new coronavirus nucleic acid test from positive to negative, fever rate, cough relief rate, chest CT improvement rate and other clinical improvements on the 7th and 14th days; and the occurrence of adverse reactions.
patients in the sample were free of chronic lung disease, chronic kidney disease, autoimmune disease, or immunodeficiency disease. No patients were admitted to the hospital with breathing difficulties, diarrhea, palpitations, or headaches. When all patients started antiviral therapy, their laboratory parameters for ALT, AST, TBIL, and creatinine were normal. At the same time, other laboratory parameters, including white blood cell count, lymphocyte count, neutral granulocyte count, C-reactive protein level and calcitonin primary level, did not differ significantly between the three groups. During the 21-day follow-up period, the average time for the detection of yang and yin in the LPV/r group was 8.5 days, 7 days in the Abidol group, and 4 days in the control group, and there was no statistical difference between them.
7 days after treatment, the negative conversion rates of 42.9% (9/21), 62.5% (10/16) and 71.4% (5/7) of the new coronavirus nucleic acid tests in the LPV/r group, the Abidol group and the control group were no statistical differences between the three groups.
14 days of treatment, the negative conversion rates of neotreaviral nucleic acid detection were 76.2% (16/21), 8
% (14/16) and 71.4% (5/7) in the three groups, and there was no statistical difference between them.
It is also worth noting that on the 7th day of treatment, 8 patients (38.1%) in the LPV/r group, 2 in the Abedore group (12.5%) and 1 (14.3%) in the control group deteriorated from mild/moderate clinical to severe/critical clinical states.
9 of the 11 patients in critical/critical condition are in serious condition and 2 are in critical condition. Two critical cases came from the LPV/r group.
two (18.2%) of these patients needed mechanical ventilation due to respiratory failure. On the 7th and 14th days, 5 (45.5%) and 8 (72.7%) cases of neovirus nucleic acid detection were turned negative, respectively. On the 7th and 14th days of treatment, chest CT imaging improved in 6 (54.5%) and 8 (72.7%) patients. At the end of the follow-up on the 21st day, 10 of them were discharged and only one was still hospitalized.
In the course of the trial, 2 patients in the LPV/r group (9.5%), 2 patients (12.5%) in the Abidor group, and 1 (14.3%) in the control group used C-type
.
In addition, 6 patients in the LPV/r group (28.6%), 2 patients in the Abidore group (12.5%) and 2 patients (28.6%) in the control group were used once a day for glucoticoids (40 mg of methyllycerid pine dragons for a total of 3-5 days). In the
LPV/r group, 18 (85.7%) patients received oxygen therapy (13 patients with low-flow oxygen supply and 5 cases with high-flow oxygen supply), while 11 in the Abidol group (68.8%, 9 cases with low-flow oxygen supply and 2 cases with high-flow oxygen supply);
During the trial, 5 patients in the LPV/r group (23.8%) experienced adverse reactions, including diarrhea (3 /21,14.3%), loss of appetite (2/21,9.5%) and ALT (transaminase) 2.5 times (1/21,4.8%) above the normal upper limit. There were no significant adverse reactions in the Abdol group or in the control group.
note that in the LPV/r group, a serious adverse reaction occurred in a 79-year-old man with underlying conditions such as diabetes and high blood pressure, who began to develop severe diarrhea on the third day of treatment. The patient was in a serious condition and tested positive for viral nucleic acid after more than 14 days of treatment, and he received in-body membrane oxygenation (ECMO) treatment, but did not recover until the end of the study. , although there was no significant difference in treatment outcomes between the three groups in the study, this could be a false negative result due to the small sample size, the researchers said. As more patients participate in the experiment in the future, more definitive conclusions will be drawn.
although the sample size is small, this study also suggests that LPV/r or Abidor monotherapy may not improve clinical outcomes in patients with mild and moderate COVID-19.
authors say the results of the study are consistent with a recent clinical trial in Wuhan of 199 patients with severe COVID-19, in which no particular benefit of LPV/r treatment was observed for patients with neocooprenia. Another clinical retrospective study of 134 patients in Shanghai also showed no effect of LPV/r and Abidor on relieving symptoms or accelerating virus removal after five days of treatment.
why LPV/r and Abigail can't benefit these patients? The authors say the reason is unclear.
They speculate that one reason may be that LPV/r and Abidor may need to increase doses to successfully suppress new coronavirus in the human body, depending on in vitro cytotoxicity tests, but given the clinical side effects of the use of these drugs, it is difficult to achieve dose increases.
particular attention is that patients treated with LPV/r have more gastrointestinal symptoms, but do not have clear antiviral effects, which may affect the patient's recovery.
, the authors say the side effects of the drug must be carefully considered in addition to its efficacy.
based on drug instructions and experience in treating people living with HIV, adverse reactions to short-term use of LPV/r include diarrhea, abnormal stools, abdominal pain, nausea, vomiting and weakness. Because these side effects can aggravate the disease, health care providers should carefully consider LPV/r treatment after weighing the risks and benefits.
Although 11 patients were treated from mild to severe/critical, at the end of the follow-up on the 21st day, 10 of them were discharged and only one was still hospitalized.
authors say this gives us confidence that even if we don't have specific antiviral drugs, the vast majority of COVID-19 patients in severe/critical clinical conditions will recover after comprehensive treatment.
addition to the small sample size, the authors noted that the study did not recruit patients with severe or multiple combinations, and that recruitment was conducted only in one center. In addition, the study did not take the form of "double blindness" entirely, so it is possible to influence the results. Researchers will continue to focus on these patients to assess their long-term prognostics.