Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Investigation and emergency management of a nosocomial infection outbreak of Omicron BA.5.1.3 strain of SARS-CoV-2

Objective: To investigate a nosocomial infection outbreak of Omicron BA.5.1.3 strain of SARS-CoV-2, and to analyze the transmission mode of Omicron BA.5.1.3 strain in hospitals, in order to evaluate the effect of nosocomial infection control and provide a basis for the epidemic prevention and control of this strain in hospitals. Methods: The onsite epidemiological methods were used to investigate the confirmed cases and their close contacts, and the prevention and control measures of nosocomial infection caused by this outbreak were studied. Results: The outbreak time of nosocomial infection was from August 4 to August 8, and the incubation period was 1-5 days, with an average incubation period of 3.0 days. The first confirmed case was a 53-year-old woman who received three doses of COVID-19 vaccine and accompanied the family of the patient in the hospital. She had traveled to a high-risk area three days before onset of the disease, and the virus type was Omicron BA.5.1.3 strain. The outbreak area was two adjacent wards of the hospital, and the incidence rates of inpatients in the two wards were 66.67% (2/3) and 33.33% (1/3), respectively. A total of 967 people were affected, including 1 imported case, 4 hospitalized cases (3 hospitalized patients and 1 nurse), 537 close contacts and 425 secondary close contacts. On August 5, the city's disease control and prevention telephone notified the first confirmed COVID-19 case. Within 0.5 hours, the ward where the case was located was sealed and static management was carried out. Measures such as district grid management, nucleic acid test in the whole hospital and in-hospital flow control were initiated. Environmental sampling, whole environment disinfection and telephone flow adjustment of case 1 were completed within 4 hours. Close contacts, secondary close contacts sampling and control were completed within 24 hours. We paid attention to the dynamics of close contacts and secondary close contacts, as if whose nucleic acid was positive, further measures could be taken to eliminate the risks. The hospital returned to normal management on August 13. Conclusion: The novel coronavirus BA.5.1.3 strain shows strong pathogenicity, short incubation period, causing overall mild disease. Timely and comprehensive prevention and control measures were the key meathods to nosocomial infection control.

Plasma 25(OH)D Level is Associated with the Nucleic Acid Negative Conversion Time of COVID-19 Patients: An Exploratory Study.

Purpose: Vitamin D, an essential nutrient and a pleiotropic steroid hormone, has been reported to be associated with the risk and severity in patients infected with Coronavirus Disease-2019 (COVID-19). The role of vitamin D in predicting clinical outcome for COVID-19 patients is unknown. Here, we aimed to determine the prognostic value of plasma 25(OH)D level in COVID-19 patients. Patients and Methods: A total of 158 patients infected with novel COVID-19 Omicron variants in Shanghai were recruited in this study and were categorized into three groups by the tertile levels of plasma 25(OH)D. Plasma 25(OH)D level was determined along with routine blood tests related to liver and renal functions in newly diagnosed COVID-19 patients at admission. The nucleic acid negative conversion time of throat swab samples was evaluated as the primary clinical outcome. The prognostic value of clinical characteristics and plasma 25(OH)D level was assessed using the Kaplan-Meier plot and Cox proportional hazards regression tests. Results: Higher level of plasma 25(OH)D level in COVID-19 patients was independently associated with shorter nucleic acid negative conversion time from COVID-19 infection (multivariate adjusted HR: 0.54, 95%CI: 0.35-0.82, P=0.004, tertile 2 vs 1; multivariate adjusted HR: 0.60, 95%CI: 0.39-0.90, P=0.014, tertile 3 vs 1). Conclusion: Plasma 25(OH)D level may serve as an independent prognostic factor in COVID-19 patient. Our findings indicate the protective roles of vitamin D supplementation in the regiment of patients with COVID-19.

Research on the Influence of Socially Regulated Learning on Online Collaborative Knowledge Building in the Post COVID-19 Period

Online teaching has become an important initiative to maintain normal educational order in the post COVID-19 period. However, learners face multiple challenges in the online learning process, which cannot be successfully carried out without the support of socially regulated learning (SoRL). This study designed SoRL intervention strategies from the perspective of shared metacognitive scripts. A total of 77 undergraduate students participated in this study and were randomly assigned into experimental and control groups. The students in the experimental group received an SoRL intervention, and the students in the control group learned with the traditional online collaborative learning approach. The results showed that there was variability in the supply of SoRL intervention scripts and the actual selection status of the learners. The regulation foci activated in this study were time management, content monitoring, and atmosphere activation. Atmosphere activation drove collaborative learning activities to continue. Time management and content monitoring drove collaborative knowledge building (CKB) to a deeper level. This study is of great significance in revealing the impact mechanism of SoRL on CKB.

Impact of the COVID-19 Pandemic and Lockdown on Anxiety, Depression and Nursing Burden of Caregivers in Alzheimer's Disease, Dementia With Lewy Bodies and Mild Cognitive Impairment in China: A 1-Year Follow-Up Study.

Background: Many countries have adopted lockdown strategies to prevent the spread of COVID-19. The goal of this study was to investigate the effects of the pandemic on anxiety, depression and care burden in caregivers of nursing patients with Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB) and Mild Cognitive Impairment (MCI), over a one-year period. Methods: We collected data on consecutive patients and their caregivers recruited at T0 (from 30 September to 31 December 2019) before the pandemic of COVID-19 at the memory clinic of Tianjin Huanhu Hospital. The patients and caregivers were followed up on face-to-face at T1 (from 30 September to 31 December 2020) during the pandemic to assess changes in physical activity, social contact, sleep quality, caregiver burden, anxiety and depression. Results: A total of 105 AD, 22 DLB and 50 MCI patients and caregivers were enrolled. A total of 36.6 % of the AD, 81.6% of the DLB, 38% of the MCI caregivers had worsening ZBI, whereas 31.7 % of the AD, 54.4% of the DLB, 26 % of the MCI caregivers had worsening GAD-7, and 29.6 % of the AD, 54.4% of the DLB, and 32 % of the MCI caregivers had worsening PHQ-9. DLB caregivers exhibited a rapid deterioration of ZBI (by 4.27 ± 5.43, P < 0.001), GAD-7 (by 2.23 ± 3.26, P = 0.003) and PHQ-9 (by 1.32 ± 2.25, P = 0.003) compared to AD and MCI caregivers. Conclusion: Social isolation, physical inactivity and sleep disturbance after lockdown for at least 12 months were significantly related to increased caregiver burden and worsened psychological states of caregivers of AD, DLB and MCI sufferers, especially among DLB caregivers.

Efficacy analysis of Arbidol treatment in patients with 2019 novel coronavirus pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to determine whether Arbidol has a good antiviral effect on coronavirus disease 2019 (COVID-19). METHODS: A retrospective cohort study was performed in one of the treatment centers for COVID-19 patients in China from January 2020 to March 2020. The antiviral drug Arbidol (ARB) was administrated to some of the patients at 0.2 g tid po for 7 to 10 days. According to whether patients were given ARB, they were divided into 2 groups: the ARB group and the Non-ARB group. The primary outcome was the 14-day COVID-19 negativity rate. RESULTS: Of 146 patients, 140 were included. A total of 79 (56.4%) patients received ARB during hospitalization. In the overall cohort, the time of COVID-19 negativity in the ARB group compared with the Non-ARB group was 12.9 days versus 12.7 days (P=0.175; >0.05). The rates of 14-day COVID-19 negativity were 60.8% and 65.6% in the ARB and non-ARB groups, respectively (P=0.559; >0.05). Using an adjusted model, there were no obvious differences in the time of COVID-19 negativity and the rates of 14-day COVID-19 negativity (P>0.05). According to Kaplan-Meier analysis, the probabilities of 14-day COVID-19 negativity were similar in the 2 groups (log-rank P=0.130; >0.05). In a multivariate Cox analysis, the variables of age [hazard ratio (HR) 0.91, 95% confidence interval (CI): 0.83 to 0.99; P=0.039] and glucose (HR 0.90, 95% CI: 0.82 to 0.98; P=0.021) were independently associated with 14-day COVID-19 negativity. CONCLUSIONS: Our results suggest that there was no apparent favorable clinical response with ARB both in clinical symptoms and the 14-day COVID-19 negativity rate.

The Impact of the COVID-19 Pandemic and Lockdown on Mild Cognitive Impairment, Alzheimer's Disease and Dementia With Lewy Bodies in China: A 1-Year Follow-Up Study.

Background: While the lockdown strategies taken by many countries effectively limited the spread of COVID-19, those were thought to have a negative impact on older people. This study aimed to investigate the impact of lockdown on cognitive function and neuropsychiatric symptoms over a 1-year follow-up period in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Methods: We enrolled consecutive patients with MCI, probable AD or DLB who were receiving outpatient memory care before the COVID-19 pandemic and followed-up with them after 1 year by face-to-face during the COVID-19 pandemic to assess changes in physical activity, social contact, cognitive function and neuropsychiatric symptoms (NPS). Results: Total 105 probable AD, 50 MCI and 22 probable DLB patients were included and completed the 1-year follow-up between October 31 and November 30, 2020. Among the respondents, 42% of MCI, 54.3% of AD and 72.7% of DLB patients had a decline in MMSE scores and 54.4% of DLB patients had worsening Neuropsychiatric inventory (NPI) scores. Patients with DLB showed a more rapid decline of MMSE than those with AD. Diminished physical activity and social contact might have hastened the deterioration of cognition and the worsening of NPS. Conclusion: Social isolation and physical inactivity even after strict lockdown for at least 6 months were correlated with accelerated decline of cognitive function and NPS in patients with AD and DLB.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients.

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

The Impact of the COVID-19 Pandemic on Alzheimer's Disease and Other Dementias.

Introduction: Numerous countries went into lockdown to contain the COVID-19 outbreak, which has impeded follow-up of chronic diseases, such as cognitive impairment (CI). Cognitive and neuropsychiatric changes during the COVID-19 pandemic are neglected in China, which is the world's whistleblower. To investigate the cognitive and neuropsychologic changes in CI, as well as the proportions of rapid cognitive decline (RCD) before and during the COVID-19 pandemic to provide clinical evidence for CI intervention during a public health emergency. Methods: We performed a descriptive and retrospective study based on medical records from the memory clinic of Tianjin Dementia Institute collected through face-to-face evaluations. Information of 205 patients with CI, including patients with mild cognitive impairment and dementia, of whom 131 with Alzheimer's disease (AD) were analyzed and compared to a control group before the COVID-19 pandemic. Results: Among the 205 CI patients, the scores on the Chinese Mini Mental State Examination (C-MMSE), the Montreal Cognitive Assessment (MoCA), activities of daily living (ADLs), and the global Neuropsychiatric Inventory (NPI) were significantly different at the baseline and follow-up evaluations (p < 0.05) after 14.07 (±2.87) months. The same findings were recorded among AD patients, and they exhibited more sleep disturbances at the follow-up than at baseline (32.8 vs. 20.6%, p = 0.035). When compared to the control group, slightly worse performance of cognitive, -1.00 (-4.00, 1.00) from the C-MMSE, -1.00 (-2.00, 0.00) on the MoCA, 1.00 (0.00, 9.00) on ADLs and neuropsychological 0.00 (-1.00, 3.50) on the global NPI profile, at the follow-up were presented, particularly for delusion, agitation, irritability, and appetite disturbances (p < 0.05). Twenty-five (19.1%) AD patients and 48 (36.6%) controls suffered RCD during the COVID-19 pandemic. Moreover, AD patients during the COVID-19 pandemic were 0.408 times (95% confidence interval: 0.232-0.716) less likely to suffer RCD than the control. Conclusion: Confinement might ease the cognitive and neuropsychiatric deterioration of AD patients compared to those not in crisis and help prevent RCD in AD patients.

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

BACKGROUND: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition. METHODS: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated. RESULTS: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (ß =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found. CONCLUSIONS: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.

Research on Sentiment Analysis Model Due to COVID-19 Using Social Media

Since the outbreak of the disease in early 2020, it has received worldwide attention and become a hot topic of discussion on social media. This paper crawled more than eight billion tweets from the first inflection point of the global outbreak of the epidemic, extracted several prominent hot topics related to the epidemic through two objective and intuitive means, namely LDA model and generated words, and then compared and analyzed the degree of subjectivity and positivity of their tweets for ‘lockdown’, ‘mental health’ and other topics. The experimental results showed that the number and active degree of global Twitter users’ tweets on the above epidemic hot topics were most correlated with the number of newly diagnosed patients after 12 days. Comments are generally more positive to lockdown than to mental health. For all tweets about the epidemic in India and Wuhan, the positive degree of tweets judged as objective was relatively stable, while the positive degree of subjective tweets fluctuated greatly, which verified the rationality and effectiveness of the model for subjective and objective classification. Among the tweets judged as subjective by the model, the positive component of sentiment analysis was more. Most tweets about the epidemic in India and Wuhan were positive, and the fluctuation degree of subjective and objective curves verified the rationality and effectiveness of the model for subjective and objective classification.

Pulmonary function of patients with 2019 novel coronavirus induced-pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the pulmonary function of patients with 2019 novel coronavirus (COVID-19)-induced pneumonia. METHODS: A retrospective analysis of 137 patients with COVID-19-induced pneumonia who were discharged from the Enze Hospital, Taizhou Enze Medical Center (Group) from January 31 2020 to March 11 2020 was conducted. Follow-up occurred 2 weeks after hospital discharge, during which patients underwent a pulmonary function test. RESULTS: Of the 137 patients who underwent a pulmonary function test 2 weeks after discharge, 51.8% were male, and the mean age was 47 years. Only 19.7% of the patients were identified as having severe COVID-19-induced pneumonia. The pulmonary function tests showed that for a small number of patients the forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC)/% values were <70%, and the mean forced inspiratory volume (IVC) and FVC values were 2.4±0.7 and 3.2±0.8 L, respectively. In severe cases, 88.9% of patients had an IVC <80% of the predicted value, and 55.6% of patients had an FVC <80% of the predicted value. The proportion of patients with maximum expiratory flow rate at 25%, 50% and 75% of the vital capacity (MEF25, MEF50, and MEF75) values <70% were 55.6%, 40.7%, and 25.9%, respectively. In the non-severe group, 79.1% of patients had an IVC <80% of the predicted value, and 16.4% of patients had an FVC <80% of the predicted value. The mean MEF25, MEF50, and MEF75 <70% values were 57.3%, 30%, and 13.6%, respectively. CONCLUSIONS: Our results demonstrated that the pulmonary function of patients with COVID-19-induced pneumonia predominantly manifested as restrictive ventilation disorder and small airway obstruction, which was increased in critically ill patients.