Clinical Characteristics of Recurrent-positive Coronavirus Disease 2019 after Curative Discharge: a retrospective analysis of 15 cases in Wuhan China

In China, the patients with previously negative RT-PCR results again test positive during the post-discharge isolation period. We aimed to determine the clinical characteristics of these "recurrent-positive" patients. We retrospectively reviewed the data of 15 recurrent-positive patients and 107 control patients with non-recurrent, moderate COVID-19 treated in Wuhan, China. Clinical data and laboratory results were comparatively analyzed. We found that recurrent-positive patients had moderate disease. The rate of recurrent-positive disease in our hospital was 1.87%. Recurrent-positive patients were significantly younger (43(35-54) years) than control patients (60(43-69) years) (P=0.011). The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive patients (36(34-45) days) than in control patients (15(7-30) days) (P =0.001). The time required for the first conversion of RT-PCR results from positive to negative was significantly longer in recurrent-positive patients (14(10-17) days) than in control patients (6(3-9) days) (P =0.011). Serum COVID-19 antibody levels were significantly lower in recurrent-positive patients than in control patients (IgM: 13.69 {+/-} 4.38 vs. 68.10 {+/-} 20.85 AU/mL, P = 0.015; IgG: 78.53 {+/-} 9.30 vs. 147.85 {+/-} 13.33 AU/mL, P < 0.0001). Recurrent-positive patients were younger than control patients. The early LOS (length of stay in hospital before recurrence) was significantly longer in recurrent-positive group than that in control group. COVID-19 IgM/IgG antibody levels were significantly lower in recurrent-positive group than those in control group, which might explain why the virus RNA RT-PCR was positive after the initial "clinical cure"(with three times of virus RNA RT-PCR negative). The virus might not be fully eliminated because of the lower IgG level and their later replicating might result in recurrent-positive virus RNA RT-PCR.

Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.

[Modelling of cerebral hyper-perfusion after chronic forebrain ischemia in rats].

OBJECTIVE: To establish the cerebral hyper-perfusion model after chronic forebrain ischemia in rats. METHODS: A total of 72 male rats were equally randomized into 2 modeling groups. The ligation of bilateral common carotid artery could induce chronic forebrain ischemia. And 36 rats were randomly grouped by ischemia duration: control group (n = 9), sham group (n = 9), 2-week ischemia group (n = 9) and 4-week ischemia group (n = 9). The blood flow in frontal lobe was measured at pre- and post-ligation. The neurological score and cerebral infarction area were also compared among the groups. The cerebral reperfusion was concurrently undertaken with an infusion dose of phenylephedrine at 4 µg×kg(-1)×min(-1) via tail vein to produce cerebrally hyperperfused blood flow rate over 200% of baseline following chronic ischemia. According to cerebral hyper-perfusion duration, 36 rats were randomly assigned into 4 groups: control group (n = 9), saline infusion group (n = 9), 30-minute cerebral hyper-perfusion group (n = 9) and 2-hour cerebral hyper-perfusion group (n = 9). The blood flow in frontal lobe was measured before and after cerebral hyper-perfusion. The neurological score, blood-brain barrier permeability and dry-wet weight ratio of brain also were compared among the groups. RESULTS: The forebrain blood flow decreased by 67% ± 2% after the ligation of bilateral common carotid artery. There was significant difference between cerebral hyper-perfusion and saline infusion groups (P < 0.01). No statistic difference was observed in neurological score and cerebral infarction area between 2-week ischemia and control groups. But it was obvious between 4-week ischemia and control groups. The permeability in blood-brain barrier of rats significantly increased in 2-hour hyper-perfusion group (P < 0.05). CONCLUSION: The 2-hour duration of cerebral hyper-perfusion following a 2-week ligation of bilateral common carotid artery may establish a reliable cerebral hyper-perfusion model in rats.

[Heat shock protein 70 induction by heat stress suppress interleukin-1beta and tumor necrosis factor-alpha levels in the brain tissue in rats with infectious brain edema].

OBJECTIVE: To investigate the changes of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the brain tissue of rats with infectious brain edema (IBE) and their relationship with heat shock protein 70 (HSP70) by heat stress response (HSR). METHODS: Seventy-two SD rats were randomly divided into normal controls group (NS group), IBE group, and HSP group, each group was divided into three subgroups. The rats in subgroups were killed at 4 hours, 8 hours and 24 hours after the injections of IBE or normal saline respectively. HSP70 in brain tissues were determined by western blot analysis. The concentrations of IL-1beta and TNF-alpha in the brain homogenate of rats were determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: The results showed that HSP70 in brain tissues were elevated after heat shock. IBE group and NS group at 4 hours, 8 hours, 24 hours were induced to base levels of HSP70. The concentrations of TNF-alpha were significantly elevated in IBE group than in NS group at the various time points (P<0.01 or P<0.05), especially at 8 hours. The concentrations of IL-1beta were significantly increased in IBE group compared with NS group at 4 hours, 8 hours. HSR reduced the IL-1beta and TNF-alpha concentrations in the brain tissue in compared with IBE group (P<0.05 or P<0.01). CONCLUSION: IL-1beta and TNF-alpha are involved in infectious brain edema by IBE. HSP70 against infectious brain edema in rats may be associated with the reduction of IL-1beta and TNF-alpha in brain tissue.

[Study of protective effect and mechanism for baicalin on bacillus pertussis infected brain tissue and its dose-effect relationship].

OBJECTIVE: To study the possible mechanism of protective effect for Baicalin on Bacillus pertussis (BP) infected brain tissue and the dose-effect relationship. METHODS: Brain tissues slices were divided into 7 groups: (1) the normal group; (2) the model group: infected by 10% BP; (3) the baicalin group, which was pretreated with baicalin, infected by BP and subdivided into 5 sub-groups according to different doses of baicalin used; (4) the glutamic acid group: cultured with glutamic acid; (5) the baicalin plus glutamic acid group; (6) the peroxide group: cultured with hydrogen peroxide; and (7) the baicalin plus peroxide group. The lactate dehydrogenase (LDH) content in the supernatant of culture was determined and quantitative protein determination was conducted. RESULTS: The LDH releasing was higher in the model group, glutamic acid group and peroxide group as compared with that in the normal group, 15.10 +/- 4.89 u/g. protein (the same unit below), 15.49 +/- 5.66 and 16.54 +/- 5.47 vs 6.10 +/- 2.87 respectively (P < 0.01). After being pretreated with 0.25 mmol/L baicalin, LDH level decreased significantly to 8.65 +/- 2.43, which was significantly different from that in the model group (P < 0.01), LDH was also decreased in the baicalin plus glutamic acid group (9.93 +/- 2.89) and baicalin plus peroxide group (9.54 +/- 2.82), which was significantly lower than that in the glutamic acid group and the peroxide group respectively (P < 0.01). CONCLUSION: Pretreatment of baicalin has protective effect on BP caused nerve cell injury in rat brain slices, the protection is possibly related with the reduction of glutamic acid and hydrogen peroxide induced damage on nerve cells in vitro.