Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Beneficial effect of Arbidol in the management of COVID-19 infection.

This study analyzed the effect of Arbidol, a broad-spectrum antiviral compound, on the outcomes of COVID-19 patients. Records of 252 COVID-19 patients were retrospectively analyzed from February 13 to February 29, 2020 in 4 inpatient wards in the Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. The rate of clinical improvement was significantly greater among patients treated with Arbidol than among those who did not receive Arbidol (86.8% vs. 54.2%). In moderately and severely ill patients, the clinical improvement rates in the Arbidol group were 95.6% and 81.7%, respectively, which was significantly higher than in the no-Arbidol group (66.6% and 53.8%). Among critically ill patients, however, there was no significant difference. The levels of hypersensitive C-reactive protein, lactate dehydrogenase, D-dimer, IL-6, and IL-10 were increased in non-improved patients but declined during treatment in the improved patients. This suggests these mediators are associated with the disease severity and could potentially serve as prognostic markers. Moreover, our data demonstrate that Arbidol is effective in the treatment of COVID-19 patients and may serve as a cost-effective antiviral treatment strategy for patients with moderate to severe COVID-19 symptoms.

Combined nucleic acid assays for diagnosis of A19 vaccine-caused human brucellosis.

Brucellosis is a common zoonotic disease caused by Brucella and is an epidemic worldwide. Currently, the most effective way to prevent and control the disease in animals is to use live, attenuated vaccines A19 strain. In China, the live attenuated Brucella abortus vaccine is widely used in animal immunization. To detect and confirm which vaccine strain caused the infection, we developed a new method to distinguish A19 strain from non-A19 strains. By comparing the genomic sequences of A19 and wild strain 2,308, we identified signature sequences that are unique to A19. A PCR assay for specific A19 identification was developed based on the genetic marker ABC transporter permease gene. Samples from the outbreak patients were then analysed using the universal quantitative PCR and A19-specific PCR assay, and the A19 strain was successfully identified in them, providing pathogenic evidence of the vaccine-derived infection outbreak. This combined A19-specific differential diagnosis method can provide a means to distinguish between animal vaccine immunization, natural infection and human infection by the vaccine strain. This strategy also has applications in diagnosis, epidemiology and surveillance of A19-related immunizations or infections.

Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment: a retrospective cohort study

ObjectivesEvaluate the risk factors of prolonged SARS-CoV-2 virus shedding and the impact of arbidol treatment on SARS-CoV-2 virus shedding. MethodsData were retrospective collected from adults hospitalized with COVID-19 in Wuhan Union Hospital. We described the clinical features and SARS-CoV-2 RNA shedding of patients with COVID-19 and evaluated factors associated with prolonged virus shedding by multivariate regression analysis. ResultsAmong 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) used arbidol, 58.4% (139/238) used arbidol combination with interferon. The median time from illness onset to start arbidol was 8 days (IQR, 5-14 days) and the median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days). SARS-CoV-2 RNA clearance was significantly delayed in patients who received arbidol >7 days after illness onset, compared with those in whom arbidol treatment was started[≤]7 days after illness onset (HR, 1.738 [95% CI, 1.339-2.257], P < .001). Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol more than seven days after symptom onset (OR 2.078, 95% CI [1.114-3.876], P .004), more than 7 days from onset of symptoms to first medical visitation (OR 3.321, 95% CI[1.559-7.073], P .002), illness onset before Jan.31, 2020 (OR 3.223, 95% CI[1.450-7.163], P .021). Arbidol combination with interferon was also significantly associated with shorter virus shedding (OR .402, 95% CI[.206-.787], P .008). ConclusionsEarly initiation of arbidol and arbidol combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

Delayed-Phase Thrombocytopenia in Patients of Coronavirus Disease 2019 (COVID-19)

The pandemic COVID-19 pneumonia has engulfed the entire world. Hematopoietic system can also be affected by COVID-19. Thrombocytopenia at admission was prevalent, while late-phase or delayed-phase thrombocytopenia is obscure. This retrospective single-center case series analyzed patients with COVID-19 at the Union Hospital, Wuhan, China, from January 25th to March 9th, 2020. Analysis began on March 11th, 2020. COVID-19 associated delayed-phase thrombocytopenia was occurred in 11.8% percent of enrolled patients. The delayed-phase thrombocytopenia in COVID-19 is prone to develop in elderly patients or patients with low lymphocyte count on admission. The delayed-phase thrombocytopenia is significantly associated with increased length of hospital stay and higher ICU admission rate. Delayed-phase nadir platelet counts demonstrated a high and significantly negative linear correlation with B cell percentages and serum IL-6 levels. We also presented bone marrow aspiration pathology of three patients with delayed-phase thrombocytopenia, showing impaired maturation of megakaryocytes. We speculated that the delayed-phase platelet destruction might be mediated by antibodies, and suggest immunoregulatory treatment in severe patients to improve outcomes. Besides, clinicians need to pay attention to the delayed-phase thrombocytopenia especially at 3-4 weeks after symptom onset.

Three-month Follow-up Study of Survivors of Coronavirus Disease 2019after Discharge

Background@#Most patients including health care workers (HCWs) survived the coronavirus disease 2019 (COVID-19), however, knowledge about the sequelae of COVID-19 after discharge remains limited. @*Methods@#A prospectively observational 3-month follow-up study evaluated symptoms, dynamic changes of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG and IgM, lung function, and high resolution computed tomography (HRCT) of survivors of COVID-19 after discharge at Wuhan Union Hospital, China. @*Results@#Seventy-six survivors (55 females) with a mean age of 41.3 ± 13.8 years were enrolled, and 65 (86%) were HCWs. A total of 69 (91%) patients had returned to their original work at 3-months after discharge. Most of the survivors had symptoms including fever, sputum production, fatigue, diarrhea, dyspnea, cough, chest tightness on exertion and palpitations in the three months after discharge. The serum troponin-I levels during the acute illness showed high correlation with the symptom of fatigue after hospital discharge (r = 0.782; P = 0.008) and lymphopenia was correlated with the symptoms of chest tightness and palpitations on exertion of patients after hospital discharge (r = −0.285, P = 0.027; r = −0.363, P = 0.004, respectively). The mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, total lung capacity and diffusion capacity were all normal (> 80% predicted) and lung HRCTs returned to normal in most of the patients (82%), however, 42% of survivors had mild pulmonary function abnormalities at 3-months after discharge. SARS-CoV-2 IgG turned negative in 11% (6 of 57 patients), 8% (4 of 52 patients) and 13% (7 of 55 patients), and SARS-CoV-2 IgM turned negative in 72% (41 of 57 patients), 85% (44 of 52 patients) and 87% (48 of 55 patients) at 1-month, 2-months and 3-months after discharge, respectively. @*Conclusion@#Infection by SARS-CoV-2 caused some mild impairments of survivors within the first three months of their discharge and the duration of SARS-CoV-2 antibody was limited, which indicates the necessity of long-term follow-up of survivors of COVID-19.

Three-month Follow-up Study of Survivors of Coronavirus Disease 2019after Discharge

Background@#Most patients including health care workers (HCWs) survived the coronavirus disease 2019 (COVID-19), however, knowledge about the sequelae of COVID-19 after discharge remains limited. @*Methods@#A prospectively observational 3-month follow-up study evaluated symptoms, dynamic changes of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG and IgM, lung function, and high resolution computed tomography (HRCT) of survivors of COVID-19 after discharge at Wuhan Union Hospital, China. @*Results@#Seventy-six survivors (55 females) with a mean age of 41.3 ± 13.8 years were enrolled, and 65 (86%) were HCWs. A total of 69 (91%) patients had returned to their original work at 3-months after discharge. Most of the survivors had symptoms including fever, sputum production, fatigue, diarrhea, dyspnea, cough, chest tightness on exertion and palpitations in the three months after discharge. The serum troponin-I levels during the acute illness showed high correlation with the symptom of fatigue after hospital discharge (r = 0.782; P = 0.008) and lymphopenia was correlated with the symptoms of chest tightness and palpitations on exertion of patients after hospital discharge (r = −0.285, P = 0.027; r = −0.363, P = 0.004, respectively). The mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, total lung capacity and diffusion capacity were all normal (> 80% predicted) and lung HRCTs returned to normal in most of the patients (82%), however, 42% of survivors had mild pulmonary function abnormalities at 3-months after discharge. SARS-CoV-2 IgG turned negative in 11% (6 of 57 patients), 8% (4 of 52 patients) and 13% (7 of 55 patients), and SARS-CoV-2 IgM turned negative in 72% (41 of 57 patients), 85% (44 of 52 patients) and 87% (48 of 55 patients) at 1-month, 2-months and 3-months after discharge, respectively. @*Conclusion@#Infection by SARS-CoV-2 caused some mild impairments of survivors within the first three months of their discharge and the duration of SARS-CoV-2 antibody was limited, which indicates the necessity of long-term follow-up of survivors of COVID-19.

Simultaneous Determination of Olanzapine, Risperidone and Paliperidone in Human Plasma by UPLC-MS/MS / 中国药房

OBJECTIVE:To develop a method for the concentration determination of olanzapine,risperidone and paliperidone in human plasma.METHODS:After liquid-liquid extraction,using buspirone hydrochloride as internal standard,the concentration of plasma sample was determined by UPLC-MS/MS.The determination was performed on ACQUITY UPLCTM BEH C18 column with mobile phase consisted of methanol-0.01 mol/L ammonium formate solution (gradient elution) at flow rate of 0.2 mL/min.The column temperature was 45 ℃,and sample size was 5 μL.The electrospray ionization source was adopted for positive ion scanning under MRM mode.Ion-pairs for quantitative analysis were as follows:m/z 313.29→256.25 (olanzapine),m/z 411.42→191.19 (ris peridone),m/z 427.45→207.18 (paliperidone) and m/z 386.43→122.37 (internal standard).RESULTS:The linear ranges of olanzapine,risperidone and paliperidone were 0.426-108.954,0.213-54.476,0.213-54.476 ng/mL,respectively.RSDs of inter-day and intra-day were all lower than 20％.The recoveries of them ranged 83.3％-112.9％,90.0％-109.8％ and 95.2％-114.9％,respective ly.Extraction recoveries ranged 65.5％-95.0％,73.9％-98.5％ and 73.6％-99.4％,respectively.Both plasma matrix effect and dilute effect didn't influence the determination of plasma concentration.The plasma concentrations of olanzapine,risperidone and paliperidone in 100 schizophrenia patients were (103.3 ± 73.6),(13.1 ± 13.1) and (23.2 ± 20.0) ng/mL,respectively.CONCLU SIONS:The method is simple,rapid,sensitive and specific.It can be used for the determination of plasma concentration and pharmacodynamic study of olanzapine,risperidone and paliperidone.