Functionalized protein microparticles targeting hACE2 as a novel preventive strategy for SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.

Age-related rhesus macaque models of COVID-19.

BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. METHODS: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

A potent, broadly protective vaccine against SARS-CoV-2 variants of concern.

Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

Impact of the COVID-19 Pandemic on Individuals With Low Vision: Life Goes On.

This qualitative case study explored the impact of lockdown and social distancing measures used during COVID-19 on the lives of individuals with low vision. A purposive sample of 6 participants with low vision was recruited. Data were collected using in-depth semistructured interviews consisting of 10 open-ended questions. A thematic analysis was conducted to understand the unified subjective experiences of the participants. The analysis revealed 4 themes: (1) Changes, a lot of them; (2) Emotional roller coaster; (3) Life goes on; and (4) Technology as the catalyst. Participants demonstrated ongoing adaptation to meet the changing demands imposed by the pandemic.

Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques.

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.

Comparative pathology of the nasal epithelium in K18-hACE2 Tg mice, hACE2 Tg mice, and hamsters infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.

Integrated histopathological, lipidomic, and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted on mink farms between minks and humans in many countries. However, the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown. Here, we demonstrated that minks were largely permissive to SARS-CoV-2, characterized by severe and diffuse alveolar damage, and lasted at least 14 days post inoculation (dpi). We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular, hepatobiliary, urinary, endocrine, digestive, and immune systems. The viral protein partially co-localized with activated Mac-2+ macrophages throughout the body. Moreover, we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks, especially at 6 dpi, and were similar to that of patients with severe and fatal COVID-19. Particularly, altered metabolic pathways, abnormal digestion, and absorption of vitamins, lipids, cholesterol, steroids, amino acids, and proteins, consistent with hepatic dysfunction, highlight metabolic and immune dysregulation. Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation. Melatonin, which has significant anti-inflammatory and immunomodulating effects, was significantly downregulated at 6 dpi and displayed potential as a targeted medicine. Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients, delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies, vaccine research, and potential biomarkers.

Community Outbreak Moderates the Association Between COVID-19-Related Behaviors and COVID-19 Fear Among Older People: A One-Year Longitudinal Study in Taiwan.

Although health behavior theories indicate that fear is effective in activating preventive behaviors, the question of whether COVID-19 severity moderates the association between fear of COVID-19 and preventive behaviors remains unclear. The present study investigated the association between the fear of COVID-19 and preventive behaviors during the COVID-19 community outbreak of two severity levels in Taiwan. Data were obtained regarding the fear of COVID-19 and practice of preventive behaviors from 139 older people (mean age = 71.73 years; 30.2% men) through in-person interviews during a mild COVID-19 outbreak period (baseline assessment). Data from 126 of the 139 participants were obtained again through a telephone interview during a severe COVID-19 outbreak period (follow-up assessment). A significant increase in the fear of COVID-19 (d = 0.39, p < 0.001) and a decrease in preventive behaviors (d = 0.63, p < 0.001) were found in the follow-up assessment. The association between fear of COVID-19 and preventive behaviors was not significant at baseline (r = -0.07, p > 0.05) but became significant at the follow-up assessment (r = 0.32, p < 0.001). The severity of a COVID-19 outbreak may alter older people's psychological status and related behaviors.

SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterol-increased endosomal pH of alveolar macrophages.

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.

Gender Differences in the Factors Associated With the Fear of COVID-19 Among Taiwanese Older People.

Objectives: Due to the COVID-19 pandemic, older people are threatened, and there may be different psychological responses toward COVID-19 between women and men. The present study explored the factors and gender differences related to the fear of COVID-19 among older women and men in Taiwan. Methods: Geriatric patients (n = 139; 42 men; mean age = 71.73 years) who visited outpatient departments were recruited. They self-reported demographic data and completed questions asking about (i) their fear of COVID-19, (ii) whether they paid attention to COVID-19 news, (iii) whether searched for COVID-19 news, (iv) whether they believed in COVID-19 news, and (v) their preventive COVID-19 behaviors. Results: Both women and men reported a low fear of COVID-19, paid close attention to COVID-19 news, and practiced good preventive COVID-19 infection behaviors. The perceived chance of COVID-19 infection was a significant factor contributing to the fear of COVID-19 among both women and men. Preventive behaviors had a positive effect in lowering the fear of COVID-19. News about COVID-19 had a negative effect in lowering the fear of the disease among women but not men. Conclusions: As the performing of preventive COVID-19 infection behaviors was associated with a lower fear of COVID-19, healthcare providers should consider strategies for improving preventive behaviors among older people to help ease their worries and fears concerning COVID-19.

Development of recombinant COVID-19 vaccine based on CHO-produced, prefusion spike trimer and alum/CpG adjuvants.

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).

Comparing Fear of COVID-19 and Preventive COVID-19 Infection Behaviors Between Iranian and Taiwanese Older People: Early Reaction May Be a Key.

This study assessed fear of the novel coronavirus-2019 (COVID-19), preventive COVID-19 infection behaviors, and the association between fear of COVID-19 and preventive COVID-19 infection behaviors among older people in Iran and Taiwan. Older people aged over 60 years (n = 144 for Iranians and 139 for Taiwanese) completed the Fear of COVID-19 Scale (FCV-19S) and two items on preventive COVID-19 infection behaviors (i.e., hand washing and mouth covering when sneezing). Iranian older people had a significantly higher level of fear of COVID-19 than did Taiwanese older people. Moreover, Iranian older people had significantly lower frequencies of preventive COVID-19 infection behaviors than did Taiwanese older people. Different timings in implementing COVID-19 infection control policies in Iran and Taiwan may explain why Iranian older people had greater fear of COVID-19 and lower preventive COVID-19 infection behaviors than did Taiwanese older people.

Post-Traumatic Stress Disorder in Chinese Teachers during COVID-19 Pandemic: Roles of Fear of COVID-19, Nomophobia, and Psychological Distress.

There are limited data concerning the prevalence of post-traumatic stress disorder (PTSD) among teachers. Therefore, the present study estimated the prevalence of PTSD among mainland Chinese teachers during the COVID-19 pandemic and to construct a model with mediation and moderation effects to explain the PTSD. Data collection was conducted in schools in the Jiangxi province between October and November 2020 among k-12 schoolteachers. An online survey, including five different psychometric scales, was used to collect data. All participants were assessed for PTSD using the Chinese version of the PTSD Checklist for DSM-5 (PCL-5). Hayes' PROCESS Model 8 was used to examine the potential factors explaining a higher PTSD scores. A total of 2603 teachers from k-12 schools participated. With the cutoff score at 31, the prevalence of PTSD was 12.3% but decreased to 1.0% when the cutoff score was at 49. Nomophobia moderated the effects of Fear of COVID-19 Scale on PTSD. The findings suggest that fear of COVID-19 among teachers leads to PTSD via psychological distress, highlighting the moderating effect of nomophobia in this association. Based on the study's findings, psychological interventions and educational training are needed to reduce fear among teachers at higher risk of developing PTSD.

[Herbalogical study on historical evolution of collection, processing and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium].

In ancient times, the original plants of Citri Exocarpium Rubrum and Citri Grandis Exocarpium had experienced succession and change, including tangerine(Citrus reticulata), pomelo(C. grandis), and Huazhou pomelo(C. grandis 'Tomentosa'), a specific cultivar of C. grandis produced in Huazhou, Guangdong. Before the Qing Dynasty, tangerine was the main original plant, while Huazhou pomelo came to the fore in the Qing Dynasty. In the 1950 s and 1960 s, the producing area of Huazhou pomelo was destroyed, and thus it had to be supplemented with pomelo. From then on, C. grandis 'Tomentosa' and C. grandis were both listed as the original plants of Citri Grandis Exocarpium in the Chinese Pharmacopoeia. This paper reviewed the historical evolution of the collection, processing, and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium. The research showed that:(1)The harvest time of the original plants of Citri Grandis Exocarpium and Citri Grandis Exocarpium had changed from maturity to immaturity. The collection and processing of Citri Exocarpium Rubrum was first recorded in the Illustrated Classics of Materia Medica in the Song Dynasty. During the Ming and Qing Dynasties, the mesocarp of Citri Exocarpium Rubrum needed to be removed completely, and Citri Grandis Exocarpium from C. grandis 'Tomentosa' was processed into different specifications such as seven-piece, five-piece, and single piece. Furthermore, processed young fruits of Huazhou pomelo appeared.(2)Citri Exocarpium Rubrum and Citri Grandis Exocarpium were processed with carp skin for the first time in the Master Lei's Discourse on Medicinal Processing. It was suggested that carp skin might be helpful for eliminating bones stuck in throat. During the Song, Jin, and Yuan Dynasties, some other processing methods such as ba-king, stir-frying, and salt-processing appeared. Honey, soil, ginger juice, and alum were firstly used as adjuvants for the processing in the Ming and Qing Dynasties. Citri Exocarpium Rubrum was mainly prepared with salt in order to improve the effect of lowering Qi, while it was unnecessary for Citri Grandis Exocarpium from C. grandis 'Tomentosa' because of its obvious effect of lowering Qi and eliminating phlegm. The stir-frying and honey-frying methods helped reduce the strong effect of Citri Grandis Exocarpium from C. grandis 'Tomentosa'.(3)According to the application of Citri Exocarpium Rubrum and Citri Grandis Exocarpium in history, their medicinal use began in Han and Tang Dynasties, developed in Song, Jin, and Yuan Dynasties, and matured in Ming and Qing Dynasties. Citri Grandis Exocarpium from C. grandis 'Tomentosa' was originally applied in Ming and Qing Dynasties, and it still plays an important in role treating COVID-19 nowadays. Moreover, Citri Grandis Exocarpium from C. grandis had cold medicinal property, while Citri Grandis Exocarpium from C. grandis 'Tomentosa' had warm medicinal property, and thus they should not be treated the same. At present, Huazhou pomelo has a certain production scale. Therefore, it is recommended that in the next edition of Chinese Pharmacopoeia, only C. grandis 'Tomentosa' should be included as the original plant of Citri Grandis Exocarpium, and C. grandis should be deleted. The results are conducive to the further development and utilization of Citri Exocarpium Rubrum and Citri Grandis Exocarpium, and support the rational use of Citri Grandis Exocarpium and its processed products.

Expanding Protection Motivation Theory to Explain Willingness of COVID-19 Vaccination Uptake among Taiwanese University Students.

Vaccination appears to be one of the effective strategies to control the COVID-19 pandemic. However, the challenge of vaccine hesitancy may lower the uptake rate and affect overall vaccine efficacy. Being a low-risk group in terms of serious consequences of infection, university students may possess low motivation to get vaccinated. Therefore, an expanded Protection Motivation Theory (PMT) incorporating perceived knowledge, adaptive response, and maladaptive response was proposed to investigate the COVID-19 vaccination intention among Taiwanese university students. University students (n = 924; 575 males; mean age = 25.29 years) completed an online survey during January to February 2021. The proposed expanded PMT model was examined using structural equation modeling (SEM). The results showed that perceived knowledge was significantly associated with coping appraisal (standardized coefficient (ß) = 0.820; p < 0.001), and coping appraisal was significantly associated with adaptive response (ß = 0.852; p < 0.001), maladaptive response (ß = 0.300; p < 0.001) and intention (ß = 0.533; p = 0.009). Moreover, maladaptive response (ß = -0.173; p = 0.001) but not adaptive response (ß = 0.148; p = 0.482) was significantly and negatively associated with intention. The present study's results demonstrated a positive path between perceived knowledge, coping appraisal, and intention among university students. Therefore, improving knowledge among this population may increase the intention to uptake the vaccine.

Internet addiction and psychological distress among Chinese schoolchildren before and during the COVID-19 outbreak: A latent class analysis.

BACKGROUND AND AIMS: The present longitudinal study examined the changes in problematic internet use (problematic smartphone use, problematic social media use, and problematic gaming) and changes in COVID-19-related psychological distress (fear of COVID-19 and worry concerning COVID-19) across three time-points (before the COVID-19 outbreak, during the initial stages of the COVID-19 outbreak, and during the COVID-19 outbreak recovery period). METHODS: A total of 504 Chinese schoolchildren completed measures concerning problematic internet use and psychological distress across three time-points. Latent class analysis (LCA) was used to classify participants into three groups of problematic internet use comprising Group 1 (lowest level), Group 2 (moderate level), and Group 3 (highest level). RESULTS: Statistical analyses showed that as problematic use of internet-related activities declined among Group 3 participants across the three time points, participants in Group 1 and Group 2 had increased problematic use of internet-related activities. Although there was no between-group difference in relation to worrying concerning COVID-19 infection, Groups 2 and 3 had significantly higher levels of fear of COVID-19 than Group 1 during the COVID-19 recovery period. Regression analysis showed that change in problematic internet use predicted fear of COVID-19 during the recovery period. CONCLUSION: The varied levels of problematic internet use among schoolchildren reflect different changing trends of additive behaviors during COVID-19 outbreak and recovery periods.

SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration.

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.

The Prevalence of Post-traumatic Stress Disorder Symptoms, Sleep Problems, and Psychological Distress Among COVID-19 Frontline Healthcare Workers in Taiwan.

The adverse effect of COVID-19 pandemic among individuals has been very disturbing especially among healthcare workers. This study aims to examine the prevalence of post-traumatic stress disorder (PTSD) symptoms, sleep problems, and psychological distress among COVID-19 frontline healthcare workers in Taiwan. Hence, a total of 500 frontline healthcare workers were recruited to participate in this cross-sectional study. They responded to measures on fear of COVID-19, depression, anxiety, stress, insomnia, PTSD, perceived stigma, and self-stigma. The results indicated a prevalence rate of 15.4% for PTSD symptoms, 44.6% for insomnia, 25.6% for depressive symptoms, 30.6% for anxiety symptoms, and 23.4% for stress among the participants. There were significantly positive interrelationships between all these variables. Anxiety symptoms and fear of COVID-19 predicted PTSD whereas symptoms of anxiety, fear of COVID-19, and stress predicted insomnia. The prevalence rates of the psychological problems reveal a worrying view of mental health challenges among Taiwanese frontline healthcare workers. Anxiety symptoms and fear of COVID-19 are the common predictive factors of PTSD and sleep problems suggesting that mental healthcare services for them may help prevent future occurrence of psychological problems by allaying fears of healthcare workers. Therefore, there should be mental healthcare services for healthcare workers during the COVID-19 pandemic.

Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and co-vaccination as an effective method of prevention of COVID-19 and influenza.

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus, leading to more serious respiratory diseases during this winter. However, the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear. Using a mammalian model, sequential infection was performed in ferrets and in K18-hACE2 mice, with SARS-CoV-2 infection following H1N1. We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19, and enhanced pulmonary damage, but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets. Moreover, mortality was increased in sequentially infected mice compared with single-infection mice. Compared with single-vaccine inoculation, co-inoculation of PiCoVacc (a SARS-CoV-2 vaccine) and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses. Combined immunization effectively protected K18-hACE2 mice against both H1N1 and SARS-CoV-2 infection. Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2, which together notably enhanced pneumonia in ferrets and mice, as well as demonstrated that simultaneous vaccination against H1N1 and SARS-CoV-2 may be an effective prevention strategy for the coming winter.