Effectiveness of telehealth interventions on psychological outcomes and quality of life in community adults during the COVID-19 pandemic: A systematic review and meta-analysis.

Physical distancing and contact restrictions have been implemented in most countries and territories due to the rapid spread of SARS-CoV-2. This has caused physical, emotional, and psychological distress for adults living in the community. Diversified telehealth interventions have been widely applied in health care and have proven to be cost-effective and well accepted by patients and health professionals. Currently, the effectiveness of telehealth interventions on psychological outcomes and quality of life among community adults during the COVID-19 pandemic remains unclear. A literature search was conducted using PubMed, PsycINFO, CINAHL, EMBASE, MEDLINE, and the Cochrane Library from 2019 to October 2022. Twenty-five randomized controlled trials with 3228 subjects were finally included in this review. Two independent reviewers performed the screening, extraction of key data points, and appraisal of the methodological quality. There were positive effects of telehealth interventions on anxiety, stress, loneliness, and well-being among community adults. Participants who were women or older adults were more likely to recover from negative emotions, increase well-being, and improve quality of life. The real-time and interactive interventions and remote cognitive-behavioural therapy (CBT) may be better choices during the COVID-19 pandemic. Based on the findings of this review, health professionals have more options and alternatives for delivering telehealth interventions in the future. Rigorously designed randomized controlled trials (RCTs) with higher statistical power and long-term follow-up should be conducted in the future to strengthen the currently weak evidence.

Nursing Home Residents' Perceptions of Challenges and Coping Strategies during COVID-19 Pandemic in China.

Older people in nursing homes are at a high risk of being infected by coronavirus disease 2019 (COVID-19). They also experienced nursing home lockdowns that harm their psychological wellbeing. Better support for this vulnerable population requires understanding their perceptions of challenges and coping strategies during the COVID-19 pandemic. A qualitative descriptive study was conducted using semi-structured interviews. Thematic analysis approach was used to analyze the data. Participants were recruited from six nursing homes in three cities in Hunan Province, China. Fourteen nursing home residents participated in the study. Four themes were identified from interviews and described as: mental stress and coping strategies, self-regulation to respond to lockdown, the lack of social connection and coping strategies, and the need for medical care services and coping strategies. This study revealed that nursing home residents perceived stress during the nursing home lockdown, but they reported initiating activities to maintain health and connections with their families and peers. Resilience improvement interventions are necessary to enable residents' autonomy and develop their resilience in coping with difficulties and hardship during crises. The findings also indicate that a supportive environment with interactions from families, peers, and staffs played a key role in enabling residents' positive health and wellbeing during the lockdown.

COVID-19 vaccination perception and uptake among cancer patients in Guangzhou, China.

Patients with cancer are considered at high risk of COVID-19 related complications with higher mortality rates than healthy individuals. This study investigated the perception, acceptance, and influencing factors of COVID-19 vaccination among cancer patients in Guangzhou, China. A cross-sectional survey was conducted in Guangzhou, China from August to November 2021 in two tertiary medical centers. Outpatients were recruited through hospital posters to complete a questionnaire including demographics, medical history, knowledge, and attitude toward COVID-19 vaccines and COVID-19 vaccination status. Chi-square tests and multivariable logistic regression were used to analyze predictors for acceptance of COVID-19 vaccination. In total, only 75 out of 343 patients (21.87%) had received at least one dose of COVID-19 vaccine. Twenty-one patients (6.12%) had received a recommendation about COVID-19 vaccination from their physicians. Patients who were recommended by physicians to get vaccinated (aOR = 11.71 95% CI: 2.71-50.66), with a monthly income of more than CNY 5000 (aOR = 3.94, 95% CI: 1.88-8.26) were more likely to have received COVID-19 vaccination. Cancer patients who had been diagnosed for more than one year (aOR = 0.21, 95% CI: 0.09-0.51), had received multiple cancer treatment strategies (aOR = 0.34, 95% CI: 0.16-0.74), worried about the safety of COVID-19 vaccines (aOR = 0.21, 95% CI: 0.11-0.40), were less likely to have received COVID-19 vaccination. COVID-19 vaccination uptake among cancer patients was insufficient. The proportion of cancer patients receiving vaccination recommendations from physicians remains inadequate. Physicians are expected to play an essential role in patients' knowledge of the safety and effectiveness of COVID-19 vaccines.

LncRNA-Mediated Adipogenesis in Different Adipocytes.

Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed.

A rare case of drug-induced bradycardia associated with the just low dose use of methylprednisolone in a child with COVID-19.

Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.

Isolation of Elizabethkingia anophelis From COVID-19 Swab Kits.

Purpose: To investigate and characterize the putative Elizabethkingia anophelis contaminant isolated from throat and anal swab samples of patients from three fever epidemic clusters, which were not COVID-19 related, in Shenzhen, China, during COVID-19 pandemic. Methods: Bacteria were cultured from throat (n = 28) and anal (n = 3) swab samples from 28 fever adolescent patients. The isolated bacterial strains were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) and the VITEK2 automated identification system. Nucleic acids were extracted from the patient samples (n = 31), unopened virus collection kits from the same manufacturer as the patient samples (n = 35, blank samples) and from unopened throat swab collection kits of two other manufacturers (n = 22, control samples). Metagenomic sequencing and quantitative real-time PCR (qPCR) detection were performed. Blood serum collected from patients (n = 13) was assessed for the presence of antibodies to E. anophelis. The genomic characteristics, antibiotic susceptibility, and heat resistance of E. anophelis isolates (n = 31) were analyzed. Results: The isolates were identified by MALDI-TOF/MS and VITEK2 as Elizabethkingia meningoseptica. DNA sequence analysis confirmed isolates to be E. anophelis. The patients' samples and blank samples were positive for E. anophelis. Control samples were negative for E. anophelis. The sera from a sub-sample of 13 patients were antibody-negative for isolated E. anophelis. Most of the isolates were highly homologous and carried multiple ß-lactamase genes (bla B, bla GOB, and bla CME). The isolates displayed resistance to nitrofurans, penicillins, and most ß-lactam drugs. The bacteria survived heating at 56°C for 30 min. Conclusion: The unopened commercial virus collection kits from the same manufacturer as those used to swab patients were contaminated with E. anophelis. Patients were not infected with E. anophelis and the causative agent for the fevers remains unidentified. The relevant authorities were swiftly notified of this discovery and subsequent collection kits were not contaminated. DNA sequence-based techniques are the definitive method for Elizabethkingia species identification. The E. anophelis isolates were multidrug-resistant, with partial heat resistance, making them difficult to eradicate from contaminated surfaces. Such resistance indicates that more attention should be paid to disinfection protocols, especially in hospitals, to avoid outbreaks of E. anophelis infection.

Recombinase polymerase amplification integrated with microfluidics for nucleic acid testing at point of care.

Nucleic acid testing (NAT) implemented on a portable, miniaturized, and integrated device with rapid and sensitive results readout is highly demanded for pathogen detection or genetic screening at resource-limited settings, especially after the outbreak of coronavirus disease 2019 (COVID-19). The integration of recombinase polymerase amplification (RPA) with emerging microfluidics, classified by paper-based microfluidics and chip-based microfluidics, shows great potential to perform laboratory independent NAT assays at point of care with minimal labor, time and energy consumption. This review summarizes the state-of-the-art of RPA integrated with paper-based microfluidics and chip-based microfluidics, and discusses their pros and cons. Finally, existing challenges and possible ways for optimization of microfluidics-based RPA are proposed.

The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice.

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.

Doctoral Journey During Covid-19: Reflections From a Collaborative Autoethnography

Aim/Purpose This paper identifies and examines cross-cutting experiences from the perspective of two doctoral students, whose research was affected by the coronavirus pandemic (COVID-19).

Achieving end-to-end success in the clinic: Pfizer's learnings on R&D productivity.

Over the past decade, Pfizer has focused efforts to improve its research and development (R&D) productivity. By the end of 2020, Pfizer had achieved an industry-leading clinical success rate of 21%, a tenfold increase from 2% in 2010 and well above the industry benchmark of ∼11%. The company had also maintained the quality of innovation, because 75% of its approvals between 2016 and 2020 had at least one expedited regulatory designation (e.g., Breakthrough Therapy). Pfizer's Signs of Clinical Activity (SOCA) paradigm enabled better decision-making and, along with other drivers (biology and modality), contributed to this productivity improvement. These laid a strong foundation for the rapid and effective development of the Coronavirus 2019 (COVID-19) vaccine with BioNTech, as well as the antiviral candidate Paxlovid™, under the company's 'lightspeed' paradigm.

Exploring the Influence of Touch Points on Tourist Experiences at Crisis Impacted Destinations

Customer journeys in tourism are becoming more complex, often including multiple touch points that can influence expectations, experiences, and travel behaviors. The management of these different interactions is further complicated if tourist destinations face natural or man-made crises (e.g., financial crises, COVID-19). The current research takes a comprehensive look at how negative word-of-mouth (WOM) shapes pre-consumption expectations that drive actual tourist experiences and subsequent satisfaction behaviors. Using partial least squares structural equation modeling (PLS-SEM), findings from 188 tourists confirm the influence of uncontrollable, negative WOM on destination image. Yet an actual, positive experience negates these negative pre-trip influences. Tourism managers are rewarded with satisfied and loyal tourists in response to creating positive experiences even at crisis impacted destinations. [ABSTRACT FROM AUTHOR] Copyright of Journal of Travel Research is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Psychological Distress, Social Support, Coping Style, and Perceived Stress Among Medical Staff and Medical Students in the Early Stages of the COVID-19 Epidemic in China.

Background: The COVID-19 pandemic has had impact that may contribute to a rise in mental health problems. The present study was aimed to better understand psychological status among medical staff and medical students during the early epidemic and to explore the influence factors of psychological distress. Methods: A cross-sectional survey was conducted online from February 2-14, 2020. We collected general information related to the COVID-19 outbreak. Respondents were assessed using the Kessler-6 Psychological Distress Scale (K6), Social Support Rating Scale (SSRS), Perceived Stress Scale (PSS) and Simplified Coping Style Questionnaire (SCSQ). Stepwise multiple linear regression was performed to identify factors influencing psychological distress. Results: Five hundred and twenty-eight respondents returned valid questionnaires. Medical staff and Medical students scored averages of 6.77 ± 5.04, 15.48 ± 8.66 on the K6, 37.22 ± 11.39, 22.62 ± 11.25 on the SSRS and 18.52 ± 7.54, 28.49 ± 11.17 on the PSS, respectively. Most medical staff (279, 91.77%) and 148 medical students (66.07%) showed a positive coping style. Social support, perceived stress, hours spent watching epidemic-related information per day and frequency of epidemic-related dreams were identified as factors influencing psychological distress among medical staff and medical students. Coping style emerged as a determinant of psychological distress among medical staff. Conclusions: In the early stages of the COVID-19 epidemic in China, medical staff and medical students were at moderate to high risk of psychological distress. Our results suggest that psychological interventions designed to strengthen social support, reduce perceived stress and adopt a positive coping style may be effective at improving the mental health of medical staff and medical students.

Nursing home staff perceptions of challenges and coping strategies during COVID-19 pandemic in China.

BACKGROUND: First-line nursing staff are responsible for protecting residents, the most vulnerable population, from COVID-19 infections. They are at a high risk of being infected with COVID-19 and experience high levels of psychological distress. AIMS: To explore the challenges and coping strategies perceived by nursing staff during the COVID-19 pandemic in China. METHODS: In April,2020, we conducted a qualitative study using in-depth semi-structured interviews with nursing staff. Participants were selected from seven nursing homes in three cities in Hunan Province, China. RESULTS: A total of 21 nursing staff participated in the study, including seven nurse managers, seven registered nurses and seven nursing assistants. Three main themes were identified. Different groups encountered different sources of stress and adopted various coping strategies to fulfil their responsibilities. CONCLUSIONS: Nursing home staff were underprepared for dealing with COVID-19-related challenges. Educational programs to improve the ability to deal with COVID-19 prevention and control are needed.

Comparative evaluation of six nucleic acid amplification kits for SARS-CoV-2 RNA detection.

BACKGROUND: SARS-CoV-2 is a newly emerged coronavirus, causing the coronavirus disease 2019 (COVID-19) outbreak in December, 2019. As drugs and vaccines of COVID-19 remain in development, accurate virus detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) kits have been reliably used for detection of SARS-CoV-2 RNA since the beginning of the COVID-19 outbreak, whereas isothermal nucleic acid amplification-based point-of-care automated kits have also been considered as a simpler and rapid alternative. However, as these kits have only been developed and applied clinically within a short timeframe, their clinical performance has not been adequately evaluated to date. We describe a comparative study between a newly developed cross-priming isothermal amplification (CPA) kit (Kit A) and five RT-qPCR kits (Kits B-F) to evaluate their sensitivity, specificity, predictive values and accuracy. METHODS: Fifty-two clinical samples were used including throat swabs (n = 30), nasal swabs (n = 7), nasopharyngeal swabs (n = 7) and sputum specimens (n = 8), comprising confirmed (n = 26) and negative cases (n = 26). SARS-CoV-2 detection was simultaneously performed on each sample using six nucleic acid amplification kits. The sensitivity, specificity, positive/negative predictive values (PPV/NPV) and the accuracy for each kit were assessed using clinical manifestation and molecular diagnoses as the reference standard. Reproducibility for RT-qPCR kits was evaluated in triplicate by three different operators using a SARS-CoV-2 RNA-positive sample. On the basis of the six kits' evaluation results, CPA kit (Kit A) and two RT-qPCR Kits (Kit B and F) were applied to the SARS-CoV-2 detection in close-contacts of COVID-19 patients. RESULTS: For Kit A, the sensitivity, specificity, PPV/NPV and accuracy were 100%. Among the five RT-qPCR kits, Kits B, C and F had good agreement with the clinical diagnostic reports (Kappa ≥ 0.75); Kits D and E were less congruent (0.4 ≤ Kappa < 0.75). Differences between all kits were statistically significant (P < 0.001). The reproducibility of RT-qPCR kits was determined using a coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility. CONCLUSIONS: This is the first comparative study to evaluate CPA and RT-qPCR kits' specificity and sensitivity for SARS-CoV-2 detection, and could serve as a reference for clinical laboratories, thus informing testing protocols amid the rapidly progressing COVID-19 pandemic.

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS-CoV-2 infection.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.

A qualitative study of the first batch of medical assistance team's first-hand experience in supporting the nursing homes in Wuhan against COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. METHOD: This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. CONCLUSIONS: It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. IMPLICATIONS: Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.

Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China.

OBJECTIVE: To estimate the prevalence of disability and anxiety in Covid-19 survivors at discharge from hospital and analyze relative risk by exposures. DESIGN: Multi-center retrospective cohort study. SETTING: Twenty-eight hospitals located in eight provinces of China. METHODS: A total of 432 survivors with laboratory-confirmed SARS CoV-2 infection participated in this study. At discharge, we assessed instrumental activities of daily living (IADL) with Lawton's IADL scale, dependence in activities of daily living (ADL) with the Barthel Index, and anxiety with Zung's self-reported anxiety scale. Exposures included comorbidity, smoking, setting (Hubei vs. others), disease severity, symptoms, and length of hospital stay. Other risk factors considered were age, gender, and ethnicity (Han vs. Tibetan). RESULTS: Prevalence of at least one IADL problem was 36.81% (95% CI: 32.39-41.46). ADL dependence was present in 16.44% (95% CI: 13.23-20.23) and 28.70% (95% CI: 24.63-33.15) were screened positive for clinical anxiety. Adjusted risk ratio (RR) of IADL limitations (RR 2.48, 95% CI: 1.80-3.40), ADL dependence (RR 2.07, 95% CI 1.15-3.76), and probable clinical anxiety (RR 2.53, 95% CI 1.69-3.79) were consistently elevated in survivors with severe Covid-19. Age was an additional independent risk factor for IADL limitations and ADL dependence; and setting (Hubei) for IADL limitations and anxiety. Tibetan ethnicity was a protective factor for anxiety but a risk factor for IADL limitations. CONCLUSION: A significant proportion of Covid-19 survivors had disability and anxiety at discharge from hospital. Health systems need to be prepared for an additional burden resulting from rehabilitation needs of Covid-19 survivors.

Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Neurological involvement in the respiratory manifestations of COVID-19 patients.

The peculiar features of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), are challenging the current biological knowledge. Early in Feb, 2020, we suggested that SARS-CoV-2 may possess neuroinvasive potential similar to that of many other coronaviruses. Since then, a variety of neurological manifestations have been associated with SARS-CoV-2 infection, which was supported in some patients with neuroimaging and/or cerebrospinal fluid tests. To date, at least 27 autopsy studies on the brains of COVID-19 patients can be retrieved through PubMed/MEDLINE, among which neuropathological alterations were observed in the brainstem in 78 of 134 examined patients, and SARS-CoV-2 nucleic acid and viral proteins were detected in the brainstem in 16/49 (32.7%) and 18/71 (25.3%) cases, respectively. To shed some light on the peculiar respiratory manifestations of COVID-19 patients, this review assessed the existing evidence about the neurogenic mechanism underlying the respiratory failure induced by SARS-CoV-2 infection. Acknowledging the neurological involvement has important guiding significance for the prevention, treatment, and prognosis of SARS-CoV-2 infection.

SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO.

Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/ß/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.