Longitudinal Assessment of Chest CT Findings and Pulmonary Function in Patients after COVID-19.

Background Information on pulmonary sequelae and pulmonary function at 2 years post recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are lacking. Purpose To longitudinally assess changes in chest CT abnormities and pulmonary function in patients after SARS-CoV-2 infection. Materials and Methods In this prospective study, patients discharged from the hospital after SARS-CoV-2 infection between January 15 and March 10, 2020 were considered for enrollment. Patients without chest CT scans on admission or with complete resolution of lung abnormities on discharge were excluded. Three serial chest CT scans and pulmonary function tests were obtained at 6 months (June 20-August 31, 2020), 12 months (December 20, 2020-February 3, 2021), and 2 years (November 16, 2021-January 10, 2022) after symptom onset. The term interstitial lung abnormalities (ILAs) and two subcategories, fibrotic ILAs and non-fibrotic ILAs, were used to describe the residual CT abnormalities on follow-up CT scans. Differences between groups were compared with χ², Fisher's exact test, or independent-samples t-test. Results Totally, 144 participants (median age, 60 [ranges 27-80] years; 79 men and 65 women) were included. On 2-year follow-up CT scans, 39% (56/144) of the subjects presented with ILAs, including 23% (33/144) wi fibrotic ILAs and 16% (23/144) with non-fibrotic ILAs. The remaining 88 cases (61%) showed complete radiological resolution. Over 2 years, the incidence of ILAs gradually decreased (54%, 42% and 39% at 6 months, 12 months and 2 years, respectively; P = .001). Respiratory symptoms (34% vs 15%, P =.007) and abnormal diffusing capacity of the lung for carbon monoxide (DLco,43% vs 20%, P = .004) more frequently occurred in participants with ILAs than those with complete radiological resolution. Conclusions More than one third of participants had persistent interstitial lung abnormalities at 2 years, which were associated with respiratory symptoms and decreased diffusion pulmonary function. See also the editorial by van Beek in this issue.

Deep Learning for Detecting COVID-19 Using Medical Images.

The global spread of COVID-19 (also known as SARS-CoV-2) is a major international public health crisis [...].

The impact of COVID-19 on firm risk and performance in MENA countries: Does national governance quality matter?

This study investigated the impact of the COVID-19 crisis on firm risk and performance in different country-level governance qualities in the MENA region. Analyzing a sample of 739 non-financial listed firms in 12 MENA countries for the period 2011-2020, we found that the COVID-19 crisis negatively impacted the performance of firms, especially low-performance firms, in most industries, and increased firm risk in general. Moreover, we found that national governance quality plays an important role in mitigating the negative impact of the COVID-19 crisis on firm operations. Specifically, national governance quality reduces the negative impact of the COVID-19 crisis on firm performance and the positive impact of the crisis on firm risk. The results are consistent with our contention that national governance quality contributes to creating a positive environment for businesses activities and reducing economic shocks.

Systemic Lupus Erythematosus Risk: The Role of Environmental Factors.

Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease. The etiology of SLE is multifactorial and includes potential environmental triggers, which may occur sequentially (the "multi-hit" hypothesis). This review focuses on SLE risk potentially associated with environmental factors including infections, the microbiome, diet, respirable exposures (eg, crystalline silica, smoking, air pollution), organic pollutants, heavy metals, and ultraviolet radiation.

Antiviral effects and tissue exposure of tetrandrine against SARS-CoV-2 infection and COVID-19.

Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS-CoV-2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS-CoV-2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu-3) cell lines. TET functioned during the early-entry stage of SARS-CoV-2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5-human angiotensin-converting enzyme 2 (hACE2)-transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS-CoV-2-infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route-dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off-target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC90) in human lungs. This study provides insights into the route-dependent pulmonary biodistribution of TET associated with its efficacy.

Shortening the biologics clinical timeline with a novel method for generating stable, high-producing cell pools and clones.

Reducing drug development timelines is an industry-wide goal to bring medicines to patients in need more quickly. This was exemplified in the coronavirus disease 2019 pandemic where reducing development timelines had a direct impact on the number of lives lost to the disease. The use of drug substances produced using cell pools, as opposed to clones, has the potential to shorten development timelines. Toward this goal, we have developed a novel technology, GPEx® Lightning, that allows for rapid, reproducible, targeted recombination of transgenes into more than 200 Dock sites in the Chinese hamster ovary cell line genome. This allows for rapid production of high-expressing stable cell pools and clones that reach titers of 4-12 g/l in generic fed-batch production. These pools and clones are highly stable in both titer and glycosylation, showing strong similarities in glycosylation profiles.

Primary Care Physicians' and Patients' Perspectives on Equity and Health Security of Infectious Disease Digital Surveillance.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic facilitated the rapid development of digital detection surveillance (DDS) for outbreaks. This qualitative study examined how DDS for infectious diseases (ID) was perceived and experienced by primary care physicians and patients in order to highlight ethical considerations for promoting patients' autonomy and health care rights. METHODS: In-depth interviews were conducted with a purposefully selected group of 16 primary care physicians and 24 of their patients. The group was reflective of a range of ages, educational attainment, and clinical experiences from urban areas in northern and southern China. Interviews were audio recorded, transcribed, and translated. Two researchers coded data and organized it into themes. A third researcher reviewed 15% of the data and discussed findings with the other researchers to assure accuracy. RESULTS: Five themes were identified: ambiguity around the need for informed consent with usage of DDS; importance of autonomous decision making; potential for discrimination against vulnerable users of DDS for ID; risk of social inequity and disparate care outcomes; and authoritarian institutions' responsibility for maintaining health data security. The adoption of DDS meant some patients would be reluctant to go to the hospital for fear of either being discriminated against or forced into quarantine. Certain groups (older people and children) were thought to be vulnerable to DDS misappropriation. CONCLUSIONS: These findings indicate the paramount importance of establishing national and international ethical frameworks for DDS implementation. Frameworks should guide all aspects of ID surveillance, addressing privacy protection and health security, and underscored by principles of social equity and accountability.Annals "Online First" article.

Miller-Fisher syndrome and Guillain-Barre syndrome overlap syndrome following inactivated COVID-19 vaccine: Case report and scope review.

Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) manifesting as the triad of ataxia, areflexia, and ophthalmoplegia. With the extensive 2019 coronavirus disease (COVID-19) immunization program, cases of GBS or MFS following vaccination are increasingly being reported. A 64-y-old Chinese man presented with new-onset paresthesia of the extremities, bilateral abduction limitation, right facial palsy, areflexia of bilateral lower limbs, and left-dominant limb ataxia 12 d after the second dose of inactivated vaccine against COVID-19. Cerebrospinal fluid analysis indicated albumin-cytological dissociation and was positive for anti-GQ1b IgG and anti-GT1b IgG. Nerve conduction studies of limbs showed evidence of axonal neuropathy with reduced sensory amplitudes. Based on the clinical presentations, temporal progression of symptoms, and laboratory findings, the diagnosis of MFS-GBS overlap syndrome was made. The patient was treated with intravenous immunoglobulin and acupuncture and made a complete recovery 54 d after the onset of his initial neurological signs. To the best of our knowledge, we report the first case of MFS-GBS overlap syndrome following the inactivated COVID-19 vaccination. However, a coincidental relationship with this inactivated vaccine cannot be excluded. Although the benefits of COVID-19 vaccination largely outweigh its risk and the prognosis of MFS is generally favorable, a close surveillance of neurological complications post-COVID-19 vaccination is always necessary, considering its potentially disabling and lethal effects on vaccinated populations.

Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases.

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.

Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells.

Viral infection often causes severe damage to the lungs, leading to the appearance of ectopic basal cells (EBCs) and tuft cells in the lung parenchyma. Thus far, the roles of these ectopic epithelial cells in alveolar regeneration remain controversial. Here, we confirm that the ectopic tuft cells are originated from EBCs in mouse models and COVID-19 lungs. The differentiation of tuft cells from EBCs is promoted by Wnt inhibition while suppressed by Notch inhibition. Although progenitor functions have been suggested in other organs, pulmonary tuft cells don't proliferate or give rise to other cell lineages. Consistent with previous reports, Trp63CreERT2 and KRT5-CreERT2-labeled ectopic EBCs do not exhibit alveolar regeneration potential. Intriguingly, when tamoxifen was administrated post-viral infection, Trp63CreERT2 but not KRT5-CreERT2 labels islands of alveolar epithelial cells that are negative for EBC biomarkers. Furthermore, germline deletion of Trpm5 significantly increases the contribution of Trp63CreERT2-labeled cells to the alveolar epithelium. Although Trpm5 is known to regulate tuft cell development, complete ablation of tuft cell production fails to improve alveolar regeneration in Pou2f3-/- mice, implying that Trpm5 promotes alveolar epithelial regeneration through a mechanism independent of tuft cells.

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0µg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.

Social Support and Depressive Symptoms Among Adolescents During the COVID-19 Pandemic: The Mediating Roles of Loneliness and Meaning in Life.

Identifying which factors influence depressive symptom during the COVID-19 pandemic is highly significant for psychological crisis interventions among adolescents. Social support is likely to be one of the main factors. However, the underlying mechanism is still not well understood in the context of COVID-19. The current study examines whether loneliness and meaning in life mediate the association between social support and depressive symptoms in adolescents. A sample of 1,317 high school students in China were surveyed using the Perceived Social Support Scale, the Chinese Child Loneliness Scale, the Meaning in Life Questionnaire, and the Beck Depression Inventory-II. The results showed that social support predicted depressive symptoms directly and indirectly by enhancing loneliness and diminishing the sense of meaning in life. These findings help in providing new entry points in the design of effective depression prevention and intervention for adolescents during the COVID-19 pandemic.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins.

The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the Omicron BA.2 spike trimer exhibits 11-fold and 2-fold higher potency in binding to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to efficiently inhibit Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants via a human-cat-mouse-human circle, which could have important implications in establishing an effective strategy for combating SARS-CoV-2 viral infections.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors.

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis, is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α-glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α-glucosidase inhibitory effect with an IC50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC50 = 24.4 ± 0.3 µM). Some interesting results of structure-activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α-glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e, 9a, 9e, and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2h. Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC50 value of 16.96 ± 2.45 µM, which was lower than the positive control Evans blue (21.98 ± 1.98 µM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l, 9a, and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α-glucosidase and SARS-CoV-2 entry inhibitors.

Recent Progress on Rapid Lateral Flow Assay-Based Early Diagnosis of COVID-19.

The outbreak of the coronavirus disease 2019 (COVID-19) has resulted in enormous losses worldwide. Through effective control measures and vaccination, prevention and curbing have proven significantly effective; however, the disease has still not been eliminated. Therefore, it is necessary to develop a simple, convenient, and rapid detection strategy for controlling disease recurrence and transmission. Taking advantage of their low-cost and simple operation, point-of-care test (POCT) kits for COVID-19 based on the lateral flow assay (LFA) chemistry have become one of the most convenient and widely used screening tools for pathogens in hospitals and at home. In this review, we introduce essential features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, compare existing detection methods, and focus on the principles, merits and limitations of the LFAs based on viral nucleic acids, antigens, and corresponding antibodies. A systematic comparison was realized through summarization and analyses, providing a comprehensive demonstration of the LFA technology and insights into preventing and curbing the COVID-19 pandemic.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11-RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

Neuropilin-1 Mediates SARS-CoV-2 Infection in Bone Marrow-derived Macrophages (preprint)

SARS-CoV-2 infection in human can cause medical complications across various tissues and organs. Despite of the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have suggested possible SARS-CoV-2 infection in human skeleton system. In the present study, we found that authentic SARS-CoV-2 could efficiently infect human and mouse bone marrow-derived macrophages (BMMs) and alter the expression of macrophage chemotaxis and osteoclast-related genes. Importantly, in a mouse SARS-CoV-2 infection model that was enabled by the intranasal adenoviral (AdV) delivery of human angiotensin converting enzyme 2 (hACE2), SARS-CoV-2 was found to be present in femoral BMMs as determined by in situ immunofluorescence analysis. Using single-cell RNA sequencing (scRNA-Seq), we characterized SARS-CoV-2 infection in BMMs. Importantly, SARS-CoV-2 entry on BMMs appeared to be dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor ACE2. It was also noted that unlike brain macrophages which displayed aging-dependent NRP1 expression, BMMs from neonatal and aged mice had constant NRP1 expression, making BMMs constantly vulnerable target cells for SARS-CoV-2. Furthermore, it was found that the abolished SARS-CoV-2 entry in BMM-derived osteoclasts was associated with the loss of NRP1 expression during BMM-to-osteoclast differentiation. Collectively, our study has suggested that NRP1 can mediate SARS-CoV-2 infection in BMMs, which precautions the potential impact of SARS-CoV-2 infection on human skeleton system.

Living with COVID-19: a phenomenological study of hospitalised patients involved in family cluster transmission.

OBJECTIVES: To describe experiences of hospitalised patients with COVID-19 following family cluster transmission of the infection and the meaning of these experiences for them. DESIGN: A descriptive phenomenological design was used to construct themes depicting patients' experiences of living with COVID-19. SETTING: This study was conducted in a major teaching hospital in Wuhan, China, in March 2020. PARTICIPANTS: Fourteen patients involved in family cluster transmission of COVID-19 were recruited into the study. The participants consisted of seven males and seven females. Data were collected through semistructured, in-depth, face-to-face interviews. Interviews were transcribed verbatim and analysed using Colaizzi's approach. RESULTS: Six themes emerged from data analysis during two distinct phases of patients going through COVID-19: the early outbreak phase and the later hospitalisation phase. Early in the outbreak, patients experienced life imbalances between individual well-being and family responsibilities. While facing widespread prejudice and rejection, patients dealt with the heavy toll that the illness had left on their body and mind. After being hospitalised, patients described feelings of living with uncertainty, sadness, fear of death and concerns about family, while simultaneously hoping for a better life after recovery. CONCLUSIONS: Our findings suggest that living with COVID-19 is an emotionally and physically challenging experience for patient participants in the study. Psychological evaluations need to be routinely carried out with patients in a public health crisis. Interprofessional and interorganisational collaborative efforts should be made to examine the physical and psychological sequelae of COVID-19, as well as investigate outcomes of existing intervention programmes.