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1.
Front Immunol ; 12: 763292, 2021.
Article in English | MEDLINE | ID: covidwho-1581338

ABSTRACT

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.


Subject(s)
Biomarkers/blood , COVID-19/immunology , Cytokines/blood , Adult , Aged , COVID-19/blood , Cytokines/immunology , Female , Hong Kong , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Severity of Illness Index
2.
JAMA Netw Open ; 4(11): e2132923, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1516695

ABSTRACT

Importance: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic. Objective: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong. Design, Setting, and Participants: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected. Main Outcomes and Measures: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein. Results: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%. Conclusions and Relevance: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.


Subject(s)
COVID-19 Testing , COVID-19/epidemiology , Pandemics , Population Health , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/virology , Communicable Disease Control , Cross-Sectional Studies , Female , Hong Kong , Humans , Immunoglobulin G/blood , Male , Middle Aged , Population Surveillance , Prevalence , Prospective Studies , RNA, Viral , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Seroepidemiologic Studies , Young Adult
3.
mBio ; 12(5): e0268721, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1494975

ABSTRACT

SARS-CoV-2 is a positive-sense single-stranded RNA virus with emerging mutations, especially on the Spike glycoprotein (S protein). To delineate the genomic diversity in association with geographic dispersion of SARS-CoV-2 variant lineages, we collected 939,591 complete S protein sequences deposited in the Global Initiative on Sharing All Influenza Data (GISAID) from December 2019 to April 2021. An exponential emergence of S protein variants was observed since October 2020 when the four major variants of concern (VOCs), namely, alpha (α) (B.1.1.7), beta (ß) (B.1.351), gamma (γ) (P.1), and delta (δ) (B.1.617), started to circulate in various communities. We found that residues 452, 477, 484, and 501, the 4 key amino acids located in the hACE2 binding domain of S protein, were under positive selection. Through in silico protein structure prediction and immunoinformatics tools, we discovered D614G is the key determinant to S protein conformational change, while variations of N439K, T478I, E484K, and N501Y in S1-RBD also had an impact on S protein binding affinity to hACE2 and antigenicity. Finally, we predicted that the yet-to-be-identified hypothetical N439S, T478S, and N501K mutations could confer an even greater binding affinity to hACE2 and evade host immune surveillance more efficiently than the respective native variants. This study documented the evolution of SARS-CoV-2 S protein over the first 16 months of the pandemic and identified several key amino acid changes that are predicted to confer a substantial impact on transmission and immunological recognition. These findings convey crucial information to sequence-based surveillance programs and the design of next-generation vaccines. IMPORTANCE Our study showed the global distribution of SARS-CoV-2 S protein variants from January 2020 to the end of April 2021. We highlighted the key amino acids of S protein subjected to positive selection. Using computer-aided approaches, we predicted the impact of the amino acid variations in S protein on viral infectivity and antigenicity. We also predicted the potential amino acid mutations that could arise in favor of SARS-CoV-2 virulence. These findings are vital for vaccine designing and anti-SARS-CoV-2 drug discovery in an effort to combat COVID-19.


Subject(s)
SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/virology , Humans , Molecular Dynamics Simulation , Phylogeny , Protein Binding , Spike Glycoprotein, Coronavirus/genetics , Virulence
4.
Microbiome ; 9(1): 91, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1183579

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. METHODS: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. RESULTS: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. CONCLUSIONS: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19. Video Abstract.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Child, Preschool , DNA , Gastrointestinal Microbiome/genetics , Humans , RNA , SARS-CoV-2 , Virome
5.
Clin Microbiol Infect ; 2021 Jan 30.
Article in English | MEDLINE | ID: covidwho-1095918

ABSTRACT

OBJECTIVES: To examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant replacement in association with containment capacity and changes in case fatality at country level. METHODS: Altogether, 69 571 full SARS-CoV-2 genomes collected globally within the first 6 months of the pandemic were examined. The correlation between variant replacement and containment capacity was examined by logistic regression models using the WHO International Health Regulation (IHR) score, the Oxford COVID-19 Government Response Tracker (OxCGRT) and the vulnerability index INFORM as proxies, while correlation with changes in monthly crude case fatality ratios was examined by a mixed effect model. RESULTS: At the global level, variant lineage G∗, characterized by the S-D614G mutation, replaced the older lineages L and S in March 2020. European countries-including Finland, France and Italy-were the first to reach a 50% increment of G∗, whereas only Singapore and South Korea had non-G∗ persisting throughout the first 6 months. Countries with higher IHR scores (ß-coefficient -0.001, 95%CI -0.016, -0.001; p 0.034) and higher stringency indexes (OxCGRT) (ß-coefficient -0.011, 95%CI -0.020, -0.001; p 0.035) were associated with lower levels of G∗ replacement, whereas higher vulnerability indexes (INFORM) (ß-coefficient 0.049, 95%CI 0.001, 0.097; p 0.044) were associated with higher replacement levels. Crude case fatality ratio showed a positive correlation with G∗ replacement (ß-coefficient: 0.034, 95%CI 0.011, 0.058; p 0.004), even after adjusting for testing capacity and other country-specific characteristics. CONCLUSIONS: SARS-CoV-2 variant lineage G∗ (S-D614G) replaced older lineages more efficiently in countries with lower containment capacity, and its possible association with increased disease severity deserves further investigation.

6.
Vaccine ; 39(7): 1148-1156, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1009913

ABSTRACT

BACKGROUND: Vaccines for COVID-19 are anticipated to be available by 2021. Vaccine uptake rate is a crucial determinant for herd immunity. We examined factors associated with acceptance of vaccine based on (1). constructs of the Health Belief Model (HBM), (2). trust in the healthcare system, new vaccine platforms and manufacturers, and (3). self-reported health outcomes. METHODS: A population-based, random telephone survey was performed during the peak of the third wave of COVID-19 outbreak (27/07/2020 to 27/08/2020) in Hong Kong. All adults aged ≥ 18 years were eligible. The survey included sociodemographic details; self-report health conditions; trust scales; and self-reported health outcomes. Multivariable regression analyses were applied to examine independent associations. The primary outcome is the acceptance of the COVID-19 vaccine. RESULTS: We conducted 1200 successful telephone interviews (response rate 55%). The overall vaccine acceptance rate after adjustment for population distribution was 37.2% (95% C.I. 34.5-39.9%). The projected acceptance rates exhibited a "J-shaped" pattern with age, with higher rates among young adults (18-24 years), then increased linearly with age. Multivariable regression analyses revealed that perceived severity, perceived benefits of the vaccine, cues to action, self-reported health outcomes, and trust in healthcare system or vaccine manufacturers were positive correlates of acceptance; whilst perceived access barriers and harm were negative correlates. Remarkably, perceived susceptibility to infection carried no significant association, whereas recommendation from Government (aOR = 10.2, 95% C.I. 6.54 to 15.9, p < 0.001) was as the strongest driving factor for acceptance. Other key obstacles of acceptance included lack of confidence on newer vaccine platforms (43.4%) and manufacturers without track record (52.2%), which are of particular relevance to the current context. CONCLUSIONS: Governmental recommendation is an important driver, whereas perceived susceptibility is not associated with acceptance of COVID-19 vaccine. These HBM constructs and independent predictors inform evidence-based formulation and implementation of vaccination strategies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Health Knowledge, Attitudes, Practice , Patient Acceptance of Health Care/statistics & numerical data , Vaccination/psychology , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Hong Kong , Humans , Male , Middle Aged , Young Adult
7.
J Infect Dis ; 222(10): 1612-1619, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-863294

ABSTRACT

BACKGROUND: Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. METHODS: We performed a prospective study in 2 regional hospitals in Hong Kong. RESULTS: We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62-0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum. CONCLUSIONS: Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Nasopharynx/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Saliva/virology , Sputum/virology , Adolescent , Adult , Aged , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/methods , Coronavirus Infections/virology , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , Prospective Studies , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Specimen Handling/methods , Young Adult
9.
BMJ Glob Health ; 5(10)2020 10.
Article in English | MEDLINE | ID: covidwho-841444

ABSTRACT

INTRODUCTION: An international city, Hong Kong, in proximity to the first epicentre of COVID- 19, experienced two epidemic waves with different importation pressure. We compared the epidemiological features of patients with COVID-19 in the context of containment policies between the first and second waves. METHODS: We retrieved information on the first 1038 cases detected in Hong Kong (23 January to 25 April 2020) to analyse the epidemiological characteristics including age/gender-specific incidence, clustering, reproduction number (Rt ) and containment delay; in relation to the containment measures implemented. Factors associated with containment delay were evaluated by multiple linear regression analysis with age, gender, epidemic wave and infection source as covariates. A time series of 5-day moving average was plotted to examine the changes across the two epidemic waves. RESULTS: The incidence and mortality (135.5 and 0.5 per 1 000 000 population) was among the lowest in the world. Aggressive escalation of border control correlated with reductions in Rt from 1.35 to 0.57 and 0.92 to 0.18, and aversions of 450 and 1650 local infections during the first and second waves, respectively. Implementing COVID-19 tests for overseas returners correlated with an upsurge of asymptomatic case detection, and shortened containment delay in the second wave. Medium-sized cluster events in the first wave were family gatherings, whereas those in the second wave were leisure activities among youngsters. Containment delay was associated with older age (adjusted OR (AOR)=1.01, 95% CI 1.00 to 1.02, p=0.040), male gender (AOR=1.41, 95% CI 1.02 to 1.96, p=0.039) and local cases (AOR=11.18, 95% CI 7.43 to 16.83, p<0.001), and with significant improvement in the second wave compared with the first wave (average: 6.8 vs 3.7 days). A higher incidence rate was observed for males, raising possibility of gender predilection in susceptibility of developing symptoms. CONCLUSION: Prompt and stringent all-round containment strategies represent successful measures in pandemic control. These findings could inform formulation and implementation of pandemic mitigation strategies.


Subject(s)
Communicable Disease Control , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Child , Child, Preschool , Communicable Disease Control/methods , Communicable Disease Control/standards , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/prevention & control , Female , Hong Kong , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Young Adult
10.
Int J Epidemiol ; 49(4): 1096-1105, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-624372

ABSTRACT

BACKGROUND: Hong Kong (HK) is a densely populated city near the epicentre of the coronavirus disease 2019 (COVID-19) outbreak. Stringent border control together with aggressive case finding, contact tracing, social distancing and quarantine measures were implemented to halt the importation and spread of the virus. METHODS: We performed an epidemiological study using government information covering the first 100 confirmed cases to examine the epidemic curve, incidence, clusters, reproduction number (Rt), incubation period and time to containment. RESULTS: A total of 93 of the 100 cases were HK residents (6 infected in Mainland China, 10 on the Diamond Princess Cruise). Seven were visitors infected in Mainland China before entering HK. The majority (76%) were aged ≥45 years, and the incidence increased with age (P < 0.001). Escalation of border control measures correlated with a decrease in the proportion (62.5% to 0%) of cases imported from Mainland China, and a reduction in Rt (1.07 to 0.75). The median incubation period was 4.2 days [95% confidence interval (CI), 4.0-4.5; 5th and 95th percentiles: 1.3 and 14.0). Most clusters with identifiable epidemiological links were households involving 2-4 people. Three medium-spreading events were identified: two from New Year gatherings (6-11 people), and another from environmental contamination of a worship hall (12 people). Despite intensified contact tracing, containment was delayed in 78.9% of cases (mean = 5.96 days, range = 0-24 days). An unusual transmission in a multi-storey building via faulty toilet plumbing was suspected with >100 residents evacuated overnight. Our analysis indicated that faulty plumbing was unlikely to be the source of this transmission. CONCLUSION: Timely stringent containment policies minimized the importation and transmission of COVID-19 in HK.


Subject(s)
Coronavirus Infections , Coronavirus , Disease Outbreaks/prevention & control , Pandemics/prevention & control , Pneumonia, Viral , Adult , Aged , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Female , Hong Kong/epidemiology , Humans , Incidence , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Psychological Distance , Quarantine , SARS-CoV-2
11.
Emerg Infect Dis ; 26(9)2020 Sep.
Article in English | MEDLINE | ID: covidwho-506041

ABSTRACT

We detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on disposable wooden chopsticks used by 5 consecutive asymptomatic and postsymptomatic patients admitted for isolation and care at our hospital. Although we did not assess virus viability, our findings may suggest potential for transmission through shared eating utensils.


Subject(s)
Betacoronavirus/genetics , Cooking and Eating Utensils , Coronavirus Infections/virology , Fomites/virology , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , COVID-19 , Coronavirus Infections/transmission , Hong Kong , Humans , Pandemics , Pneumonia, Viral/transmission , SARS-CoV-2 , Wood/virology
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