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1.
Adv Exp Med Biol ; 1318: 499-515, 2021.
Article in English | MEDLINE | ID: covidwho-1222732

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease that can rapidly escalate to respiratory failure and death. It has infected millions of people worldwide. The trajectory of this disease continues to progress in some areas of the United States and worldwide. The Institute for Health Metrics now predicts a resurgence of infections in the fall of 2020. The pathogenesis of COVID-19 includes an inflammatory phase with either resolution or the potential to accelerate to a cytokine storm, characterized by high interleukin (IL)-6 and other inflammatory markers. COVID-19 is a condition without a gold-standard treatment. The US Federal Drug Administration (FDA) issued an emergency use authorization for remdesivir in severe cases of COVID-19, which shortened the recovery time in hospitalized patients with lower respiratory tract infection in one study. Although several vaccine trials are underway, no vaccines are available for primary prevention of COVID-19 at this time. Dietary supplement sales have dramatically risen during the COVID-19 pandemic despite depressed economic conditions. Commonly used immune-modulating dietary supplements, including vitamin D, ascorbic acid, zinc, and melatonin, are reviewed in this manuscript highlighting biological plausibility for salutary benefit against COVID-19. Ongoing clinical trials recruiting subjects at the time of this writing are provided for each dietary supplement.


Subject(s)
Pandemics , Dietary Supplements , Humans , United States/epidemiology , Vitamin D
2.
Acta Pharmacol Sin ; 2021 Apr 27.
Article in English | MEDLINE | ID: covidwho-1205431

ABSTRACT

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

3.
Engineering (Beijing) ; 2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1198742

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic increased the burden on many healthcare systems and in the process, exposed the need for medical resources and physical space. While few studies discussed the efficient utilization of medical resources and physical space so far. Therefore, this study aimed to summarize experiences related to facilities used for centralized isolation for medical observation and treatment during the COVID-19 pandemic in China and to provide suggestions to further improve the management of confirmed cases, suspected cases, and close contacts. In China, three types of facilities for centralized isolation (Fangcang shelter hospitals, refitted non-designated hospitals, and quarantine hotels) underwent retrofitting for the treatment and isolation of confirmed and suspected cases. These facilities mitigated the immediate high demand for space. Moreover, in order to minimize infection risks in these facilities, regulators and governmental agencies implemented new designs, management measures, and precautionary measures to minimize infection risk. Other countries and regions could refer to China's experience in optimally allocating social resources in response to the COVID-19 pandemic. As a conclusion, government should allocate social resources and construct centralized isolation and quarantine facilities for an emergency response, health authorities should issue regulations for centralized isolation facilities and pay strict attention to the daily management of these facilities, a multidisciplinary administration team is required to support the daily operation of a centralized isolation facility, in-depth studies and international collaboration on the centralized isolation policy are encouraged.

4.
Int J Biol Sci ; 17(5): 1277-1288, 2021.
Article in English | MEDLINE | ID: covidwho-1191953

ABSTRACT

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo. Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro. Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.


Subject(s)
/pathology , Cell Differentiation , Fracture Healing , MicroRNAs/metabolism , Osteogenesis , /physiology , Adult , Aged , Aged, 80 and over , /virology , Female , Humans , Male , Middle Aged , Toll-Like Receptor 4/metabolism
6.
EBioMedicine ; 66: 103319, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1174196

ABSTRACT

BACKGROUND: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. METHODS: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. FINDINGS: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades 'O' were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. INTERPRETATION: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.

7.
Lancet Infect Dis ; 2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-1164676

ABSTRACT

BACKGROUND: The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19. METHODS: This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors. FINDINGS: Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission. INTERPRETATION: Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted. FUNDING: Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.

8.
Lancet Microbe ; 2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1155679

ABSTRACT

Background: Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. Methods: We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. Findings: We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (52 [29%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Interpretation: Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphasise the importance of public health and social measures in the ongoing pandemic outbreak response, and might have implications for longevity of immunity after vaccination. Funding: National Medical Research Council, Biomedical Research Council, and A*STAR, Singapore.

9.
Farm Hosp ; 45(2): 89-95, 2021 Feb 22.
Article in English | MEDLINE | ID: covidwho-1154798

ABSTRACT

All over the world pharmacists are standing up to the challenge of COVID- 19 and showing their commitment to the communities they serve. As the COVID-19 pandemic has tested global health systems to their limits, pharmacy professionals have shown themselves to be an integral part of them. Community pharmacists have supported government initiatives to control the pandemic and have ensured patients continued to receive their medicines. Hospital pharmacists have been moving beyond their specialties to help provide critical care to patients while dealing with ICU drug shortages. Pharmaceutical scientists have been involved in finding effective vaccines and identifying effective treatments. In short, the pharmacy profession has been demonstrating expertise, strength, courage and dedication to care at the highest level. The International Pharmaceutical Federation (FIP), which represents the pharmacy profession globally, has a mission to advance pharmacy worldwide by sharing best pharmacy practice and innovation with the world. In this article, it describes how pharmacy has stepped up during the COVID­19 crisis by giving examples from several countries. It highlights, for example, how virtual practice became more prominent as face-to-face meetings became impossible, how pharmacists' scope of practice has been extended, and how pharmacy educators have embraced digital technologies to teach and assess students remotely. In particular, the article highlights pharmacists' involvement in the COVID-19 vaccination programmes in Australia, Canada, Germany, Ireland, Switzerland, the UK and the USA. As a result of all this, FIP sees an exciting future for the profession. Health ministers and heads of state have been praising pharmacists for their service, and FIP wants governments to translate this recognition into support for expanded roles and scientific research. It continues to gather data and intelligence to support an expansion of pharmacy practice, education and pharmaceutical workforce that builds on the profession's scientific base. All these advances are supported by scientific studies about our specialty. Finally, FIP expresses its worries about equity of access to medicines during the pandemic, as younger, healthier people in rich countries are vaccinated before people at greater risk in poor countries. It insists it will continue to advocate on this topic as a core component of its global vision. In this article, we share with readers a snapshot of how our profession around the world has adapted to the challenges posed by the COVID-19 pandemic, and our thoughts on the how it is affecting the evolution of pharmacy practice.


Subject(s)
Pharmacists , Pharmacy , Professional Role , Global Health , Humans
10.
Biosci Trends ; 15(2): 129-131, 2021 May 11.
Article in English | MEDLINE | ID: covidwho-1154738

ABSTRACT

During the COVID-19 pandemic, frontline nurses have faced extraordinary personal and professional challenges. These challenges have had mental health consequences, and concerning reports of burnout have emerged globally. We conducted a cross-sectional survey at a designated COVID-19 hospital in Shanghai at the peak of the pandemic, i.e. about 2 months after the onset of the outbreak from February to April 2020. Findings revealed burnout in 6.85% of nurses. Of 336 respondents, 87 (25.89%) had a high level of emotional exhaustion, 61 (18.15%) had a high level of depersonalization, and 100 (29.76%) had a low level of personal accomplishment. Burnout can be prevented by offering more support from families and supervisors, paying attention to health monitoring and personal protection, and creating a rational human resource allocation and shift management system. Specific training on infection control and self-protection, mental health guidance, and stress coping techniques must be implemented. As the current health crisis ultimately abates, moving the focus from mental health issues to public health issues, more attention and support at the national and organizational levels are needed to reduce occupational discrimination, nurse autonomy and status need to be promoted, and public health emergency teams need to be created. A positive and fair working environment is essential to effective healthcare delivery.

11.
Infect Dis Poverty ; 10(1): 37, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1150428

ABSTRACT

BACKGROUND: The COVID-19 has caused significant toll over the globe. Pregnant women are at risk of infection. The present study examined the frequency of washing hands with soap and wearing face mask when going out, prevalence of depression and anxiety, and identified their associated factors among pregnant women during the early phase of COVID-19 outbreak in China. METHODS: A cross-sectional online survey was conducted between 24 February and 3 March 2020. A total of 15 428 pregnant women who were using maternal health care services in China completed a questionnaire which assessed their socio-demographic and pregnancy-related characteristics, contextual, cognitive and social factors related to COVID-19, frequency of washing hands and wearing face masks, and depression and anxiety. Logistics regression analyses were performed to identify the associated factors of preventive behaviours and mental health. RESULTS: The prevalence of probable anxiety and depression was 28.2% and 43.6% respectively. 19.8% reported always wearing face mask when going out, and 19.1% reported washing hands with soap for more than 10 times per day. Results from logistic regression analyses showed that older age was associated with lower levels of depression and anxiety (OR = 0.42-0.67) and higher frequency of washing hands (OR = 1.57-3.40). Higher level of education level was associated with probable depression (OR = 1.31-1.45) and higher frequency of wearing face mask (OR = 1.50-1.57). After adjusting for significant socio-demographic and pregnancy-related factors, place of residence being locked down (aOR = 1.10-1.11), being quarantined (aOR = 1.42-1.57), personally knowing someone being infected with COVID-19 (aOR = 1.80-1.92), perception that COVID-19 would pose long term physical harm to human (aOR = 1.25-1.28) were associated with higher levels of depression and anxiety, while the perception that the disease will be under control in the coming month was associated with lower levels of depression and anxiety (aOR = 0.59-0.63) and lower tendency of always wearing face mask (aOR = 0.85). Social support was associated with lower levels of depression and anxiety (aOR = 0.86-0,87) and higher frequency of washing hands (aOR = 1.06). CONCLUSIONS: The mental health and preventive behaviours of pregnant women during COVID-19 outbreak was associated with a range of socio-demographic, pregnancy-related, contextual, cognitive and social factors. Interventions to mitigate their mental health problems and to promote preventive behaviours are highly warranted.


Subject(s)
/prevention & control , Health Behavior , Mental Health , Pregnancy Complications, Infectious/prevention & control , Adult , Age Factors , China , Depression/epidemiology , Educational Status , Female , Hand Disinfection/trends , Humans , Logistic Models , Maternal Health Services/statistics & numerical data , Odds Ratio , Personal Protective Equipment , Pregnancy , Pregnancy Complications, Infectious/psychology , Prenatal Care , Prevalence , Risk Factors , Social Support , Surveys and Questionnaires , Young Adult
12.
Emerg Infect Dis ; 27(5): 1527-1529, 2021 05.
Article in English | MEDLINE | ID: covidwho-1148279

ABSTRACT

A fast-spreading severe acute respiratory syndrome coronavirus 2 variant identified in the United Kingdom in December 2020 has raised international alarm. We analyzed data from 15 countries and estimated that the chance that this variant was imported into these countries by travelers from the United Kingdom by December 7 is >50%.

13.
Infect Dis Ther ; 2021 Mar 14.
Article in English | MEDLINE | ID: covidwho-1130961

ABSTRACT

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a severe respiratory disease with a 3% global mortality. In the absence of effective treatment, controlling of risk factors that predispose to severe disease is essential to reduce coronavirus disease 2019 (COVID-19) mortality. Large observational studies suggest that exercise can reduce the risk of all-cause and disease-specific mortality. The aim of this study was to analyze the influence of the baseline physical activity level on COVID-19 mortality METHODS: This is a retrospective cohort study that included patients between 18 and 70 years old, diagnosed with COVID-19 and hospitalized in our center between February 15 and April 15, 2020. After discharge all the patients included in the study were contacted by telephone. Baseline physical activity level was estimated using the Rapid Assessment of Physical Activity Scale questionnaire and patients were divided into two groups for comparison: sedentary patients (group 1) and active patients (group 2). RESULTS: During the study period 552 patients were admitted to our hospital and met the inclusion criteria. Global mortality in group 1 was significantly higher than in group 2 (13.8% vs 1.8%; p < 0.001). Patients with a sedentary lifestyle had increased COVID-19 mortality independently of other risk factors previously described (hazard ratio 5.91 (1.80-19.41); p = 0.003). CONCLUSION: A baseline sedentary lifestyle increases the mortality of hospitalized patients with COVID-19. This finding may be of great utility in the prevention of severe COVID-19 disease.

14.
JAMA Netw Open ; 4(3): e212574, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1126330

ABSTRACT

Importance: Face masks are recommended to prevent transmission of coronavirus disease 2019 (COVID-19); however, there is scarce evidence on their protection efficacy and ways to improve it. Objective: To determine the proportion of improper face mask use, the factors associated with face mask protection efficacy, and ways to improve efficacy. Design, Setting, and Participants: This population-based cross-sectional study was conducted in China from July to August 2020 in 5 kinds of public places. Participants included convenience samples of individuals wearing face masks and able to taste the check solution. Exposures: Demographic and socioeconomic characteristics, including sex, age, and education level; information on face mask model and the worn duration was recorded. Main Outcomes and Measures: The main outcome as airtightness, assessed by detecting face-to-face mask gaps, movement of cotton fiber placed at the face mask edges, and using a qualitative fit test with a bitter solution spray. Masks were further assessed for whether sealing the upper face mask edge with an adhesive tape strip was associated with improved face mask airtightness. Results: Among 6003 face mask wearers enrolled, the mean (SD) age of participants was 31.1 (13.7) years, and 3047 participants (50.8%) were female. The first qualitative fit test found air leakage in 2754 participants (45.9%; 95% CI, 44.6%-47.1%), which was mostly attributable to gaps at the upper face mask edge. After sealing the upper face mask edge with an adhesive tape strip, 69.7% (95% CI, 68.0%-71.5%) of masks that had exhibited leakage became airtight in the second qualitative fit test, and the rate of airtightness reached 96.2% (95% CI, 95.4%-96.8%) in a third qualitative fit test after new surgical face masks with tape on the upper edge were provided to those who had not converted initially. The tape was well tolerated; overall, 6 participants (1.2%) reported a rash and 24 participants (5.8%) reported significant discomfort. Conclusions and Relevance: In this study of face mask fit among participants in China, although most people used face masks in public places, compromised protection due to suboptimal airtightness was common. The simple approach of sealing the upper edge of the face mask with an adhesive tape strip was associated with substantially improved its airtightness.


Subject(s)
/prevention & control , Cotton Fiber , Disposable Equipment , Masks , Adult , China , Cross-Sectional Studies , Female , Humans , Male , Young Adult
15.
Front Immunol ; 11: 580237, 2020.
Article in English | MEDLINE | ID: covidwho-1116681

ABSTRACT

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results: The counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

16.
Nat Rev Immunol ; 21(5): 269-271, 2021 05.
Article in English | MEDLINE | ID: covidwho-1116029
17.
Nat Ecol Evol ; 5(5): 600-608, 2021 05.
Article in English | MEDLINE | ID: covidwho-1111986

ABSTRACT

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.


Subject(s)
Chiroptera , Animals , Humans , Peptidyl-Dipeptidase A/genetics , Receptors, Virus/genetics , Spike Glycoprotein, Coronavirus/genetics
18.
J Exp Med ; 218(5)2021 05 03.
Article in English | MEDLINE | ID: covidwho-1109140

ABSTRACT

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2-specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2-specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1ß) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2-infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.


Subject(s)
Asymptomatic Infections , Cytokines/immunology , Lymphocyte Activation , T-Lymphocytes/immunology , Adult , Cytokines/blood , Humans , Male , Middle Aged , T-Lymphocytes/metabolism
19.
Int J Environ Res Public Health ; 18(4)2021 02 18.
Article in English | MEDLINE | ID: covidwho-1102526

ABSTRACT

Coronavirus disease 2019 (COVID-19) occurred in Wuhan and rapidly spread around the world. Assessing the impact of COVID-19 is the first and foremost concern. The inflection point (IP) and the corresponding cumulative number of infected cases (CNICs) are the two viewpoints that should be jointly considered to differentiate the impact of struggling to fight against COVID-19 (SACOVID). The CNIC data were downloaded from the GitHub website on 23 November 2020. The item response theory model (IRT) was proposed to draw the ogive curve for every province/metropolitan city/area in China. The ipcase-index was determined by multiplying the IP days with the corresponding CNICs. The IRT model was parameterized, and the IP days were determined using the absolute advantage coefficient (AAC). The difference in SACOVID was compared using a forest plot. In the observation study, the top three regions hit severely by COVID-19 were Hong Kong, Shanghai, and Hubei, with IPcase indices of 1744, 723, and 698, respectively, and the top three areas with the most aberrant patterns were Yunnan, Sichuan, and Tianjin, with IP days of 5, 51, and 119, respectively. The difference in IP days was determined (χ2 = 5065666, df = 32, p < 0.001) among areas in China. The IRT model with the AAC is recommended to determine the IP days during the COVID-19 pandemic.


Subject(s)
/epidemiology , Pandemics , China/epidemiology , Cities , Hong Kong , Humans
20.
J Pediatr Hematol Oncol ; 2021 Mar 31.
Article in English | MEDLINE | ID: covidwho-1099654

ABSTRACT

Data regarding the epidemiologic characteristics and clinical features of pediatric hematological patients are limited in this corona virus disease 2019 (COVID-19) crisis. We investigated the status of 113 pediatric hematological patients in Wuhan union hospital during the COVID-19 pandemic from January 23 to March 10, 2020. All the patients had routine blood and biochemical examination, as well as chest computed tomography scans, and the nucleic acid, immunoglobulin G-immunoglobulin M combined antibodies tests for SARS-CoV-2. After admission, all patients were single-room isolated for 5 to 7 days. The results showed that only 1 (0.88%) child with leukemia was confirmed to have SARS-CoV-2 infection and 15 (13.2%) children were considered as suspected cases. Comparing to the nonsuspected patients, the suspected cases had lower white blood cell count, hemoglobin level, neutrophil count, serum calcium ion level and serum albumin concentration, as well as higher levels of C-reactive protein. All the suspected cases were ruled out of SARS-CoV-2 infection by twice negative tests for the virus. Therefore, the incidence of SARS-CoV-2 infection in hematological malignancy children was low during the COVID-19 pandemic in China. COVID-19 got early detected and the virus spread out in the ward was effectively blocked by increasing test frequency and using single-room isolation for 5 to 7 days after admission.

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