Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
1.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-331885

ABSTRACT

Background: Data on the impact of dysnatraemia and pre-existing hyponatraemia on clinical outcomes of COVID-19 remains elusive. Methods: We performed a territory-wide retrospective cohort study of COVID-19 patients between 23 January 2020 and 1 January 2021 in Hong Kong. The primary endpoint was all-cause mortality. The secondary endpoint was intensive care unit (ICU) admission and/or use of invasive mechanical ventilation (IMV). Mild hyponatraemia, moderate-to-severe hyponatraemia, normonatraemia, and hypernatraemia were defined as serum sodium of 130-<135, <130, 135-145, and >145 mmol/L , respectively. Background sodium level was measured at least one month before COVID-19 diagnosis. Findings: Of 8,407 patients, 738 (8·8%), 143 (1·7%), and 24 (0·3%) had mild hyponatraemia, moderate-to-severe hyponatraemia, and hypernatraemia at COVID-19 diagnosis, respectively. At a median follow-up of 12 days, 156 (1·9%) patients died;413 (4·9%) patients were admitted to ICU and/or required IMV use. Moderate-to-severe hyponatraemia (adjusted hazard ratio [aHR] 2·92, 95% CI 1·59–5·36, P<0·001) and hypernatraemia (aHR 7·60, 95% CI 5·16–11·20, P <0·001) were independently associated with an increased mortality rate . Mild (adjusted cause-specific HR [aCSHR] 1·94) and moderate-to-severe hyponatraemia (aCSHR 2·08) were independently associated with a higher rate of ICU admission/IMV use. Hypernatraemia was not associated with a higher rate of ICU admission/IMV use, yet was associated with a higher rate of competing death. Background hyponatraemia was associated with a higher rate of mortality. Interpretation: COVID-19 patients with dysnatraemia are associated with adverse clinical outcomes, in whom vigilant monitoring of serum sodium would be important.

2.
Pathogens ; 11(4):397, 2022.
Article in English | MDPI | ID: covidwho-1762173

ABSTRACT

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. Methods: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. Results: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF 'receptor-blocking';S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. Conclusions: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection.

3.
Microbiol Spectr ; : e0018222, 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1752768

ABSTRACT

SARS-CoV-2 transcribes a set of subgenomic RNAs (sgRNAs) essential for the translation of structural and accessory proteins to sustain its life cycle. We applied RNA-seq on 375 respiratory samples from individual COVID-19 patients and revealed that the majority of the sgRNAs were canonical transcripts with N being the most abundant (36.2%), followed by S (11.6%), open reading frame 7a (ORF7a; 10.3%), M (8.4%), ORF3a (7.9%), ORF8 (6.0%), E (4.6%), ORF6 (2.5%), and ORF7b (0.3%); but ORF10 was not detected. The profile of most sgRNAs, except N, showed an independent association with viral load, time of specimen collection after onset, age of the patient, and S-614D/G variant with ORF7b and then ORF6 being the most sensitive to changes in these characteristics. Monitoring of 124 serial samples from 10 patients using sgRNA-specific real-time RT-PCR revealed a potential of adopting sgRNA as a marker of viral activity. Respiratory samples harboring a full set of canonical sgRNAs were mainly collected early within 1 to 2 weeks from onset, and most of the stool samples (90%) were negative for sgRNAs despite testing positive by diagnostic PCR targeting genomic RNA. ORF7b was the first to become undetectable and again being the most sensitive surrogate marker for a full set of canonical sgRNAs in clinical samples. The potential of using sgRNA to monitor viral activity and progression of SARS-CoV-2 infection, and hence as one of the objective indicators to triage patients for isolation and treatment should be considered. IMPORTANCE Attempts to use subgenomic RNAs (sgRNAs) of SARS-CoV-2 to identify active infection of COVID-19 have produced diverse results. In this work, we applied next-generation sequencing and RT-PCR to profile the full spectrum of SARS-CoV-2 sgRNAs in a large cohort of respiratory and stool samples collected throughout infection. Numerous known and novel discontinuous transcription events potentially encoding full-length, deleted and frameshift proteins were observed. In particular, the expression profile of canonical sgRNAs was associated with genomic RNA level and clinical characteristics. Our study found sgRNAs as potential biomarkers for monitoring infectivity and progression of SARS-CoV-2 infection, which provides an alternative target for the management and treatment of COVID-19 patients.

4.
Clin Exp Ophthalmol ; 2022 Feb 26.
Article in English | MEDLINE | ID: covidwho-1714157

ABSTRACT

BACKGROUND: We investigated the ocular surface disturbances in COVID-19 patients discharged from the hospital. METHODS: One hundred and seventy-nine eyes of 109 healthy participants and 456 eyes of 228 post-COVID-19 patients received comprehensive eye examinations; the latter were interviewed with questionnaires on ocular symptoms before and after COVID-19 diagnosis. Associations of ocular surface manifestations with virological and ophthalmic parameters were evaluated by multivariable mixed linear or logistic regression models. RESULTS: Mean interval between COVID-19 diagnosis and ophthalmic evaluation was 52.23 ± 16.12 days. The severity of meibomian gland dysfunction (MGD) based on clinical staging was higher in post-COVID-19 than healthy eyes (1.14 ± 0.67 vs. 0.92 ± 0.68, p = 0.002) and so was ocular surface staining score (0.60 ± 0.69 vs. 0.49 ± 0.68, p = 0.044). Patients requiring supplementary oxygen during hospitalisation had shorter tear break-up time (ß -1.63, 95% CI -2.61 to -0.65). Cycle threshold (Ct) value from upper respiratory samples (inversely correlated with viral load) at diagnosis had an OR = 0.91 (95% CI 0.84-0.98) with new ocular surface symptoms 4 weeks after diagnosis. The presence of ocular surface symptoms 1 week prior to COVID-19 diagnosis showed an OR of 20.89 (95% CI 6.35-68.66) of persistent or new ocular symptoms 4 weeks afterward. CONCLUSIONS: MGD and ocular surface staining are more common and severe in post-COVID-19 patients. Patients with higher viral loads have greater risks of ocular surface symptoms. Patients requiring supplementary oxygen are more likely to show tear film instability. Ocular surface evaluation should be considered 1-3 months following hospital discharge for any COVID-19 patient.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325537

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 faecal 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 faecal 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 faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal 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 faecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured 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.

6.
J Gastroenterol Hepatol ; 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1685355

ABSTRACT

BACKGROUND AND AIM: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS: Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS: This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.

7.
J Clin Virol Plus ; 2(1): 100062, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1616571

ABSTRACT

Objectives: Little is known whether differences exist in virus shedding, immune and inflammatory response related to SARS-CoV-2 in people living with human immunodeficiency virus (PLWH). We assessed viral RNA and cytokine profiles of HIV and SARS-CoV-2 coinfection in Hong Kong. Methods: PLWH hospitalized with SARS-CoV-2 infection in Hong Kong were included, compared with age-matched and disease severity-matched SARS-CoV-2 infected controls (ratio of 1:5) from February 1st 2020 to July 31st 2020. SARS-CoV-2 infection was confirmed by public health laboratory and virus concentration was quantified by an in-house real-time reverse transcription-quantitative polymerase chain reaction. A panel of cytokines and chemokines were performed. Results: HIV patients had a similar respiratory shedding profile compared to controls. Duration of faecal shedding of patient A, B, C and D were at least 9, 10, 33, and 11 days, respectively. HIV patients had lower plasma levels of IL-10 and NT-pro-BNP. All 4 PLWH cases showed seroconversion to SARS-CoV-2 with anti-SARS-CoV-2 S antibodies detected in serum collected between day 18 and 30 after symptom onset. Conclusions: PLWH behaves similarly with HIV-negative controls in respiratory viral load, but with decrease in IL-10 and NT-proBNP. PLWH may have a lower risk of immunostimulatory effect due to lower IL-10.

8.
Clin Infect Dis ; 73(7): e1782-e1783, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1584993

Subject(s)
Wolves , Animals
9.
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
10.
Respirology ; 27(4): 301-310, 2022 04.
Article in English | MEDLINE | ID: covidwho-1532912

ABSTRACT

BACKGROUND AND OBJECTIVE: Few head-to-head evaluations of immune responses to different vaccines have been reported. METHODS: Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells. RESULTS: One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50 , PRNT90 , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T-cell responses. CONCLUSION: Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4+ and CD8+ T-cell responses to the structural protein than BNT162b2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , COVID-19/prevention & control , Hong Kong , Humans , Leukocytes, Mononuclear , SARS-CoV-2
11.
Gastroenterology ; 162(2): 548-561.e4, 2022 02.
Article in English | MEDLINE | ID: covidwho-1475507

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2-infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution. METHODS: We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non-COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites. RESULTS: Compared with non-COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05). CONCLUSIONS: Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome.


Subject(s)
COVID-19/microbiology , Fatty Acids, Volatile/biosynthesis , Gastrointestinal Microbiome/genetics , Immunity/physiology , Isoleucine/biosynthesis , Adult , Biomarkers/blood , Case-Control Studies , Feces/microbiology , Female , Humans , Male , Metagenomics , Middle Aged , Phylogeny , SARS-CoV-2 , Severity of Illness Index
14.
Hepatology ; 74(4): 1750-1765, 2021 10.
Article in English | MEDLINE | ID: covidwho-1274697

ABSTRACT

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P < 0.001), but not current (aHR, 1.29; 95% CI, 0.61-2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56-1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir-ritonavir (adjusted OR [aOR], 2.55-5.63), but not current (aOR, 1.93; 95% CI, 0.88-4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62-2.55; P = 0.533) HBV infection, was associated with acute liver injury. CONCLUSION: Current or past HBV infections were not associated with more liver injury and mortality in COVID-19.


Subject(s)
Acute Lung Injury/epidemiology , COVID-19/mortality , Hepatitis B, Chronic/epidemiology , Acute Lung Injury/blood , Acute Lung Injury/diagnosis , Acute Lung Injury/virology , Adult , Age Factors , Aged , Alanine Transaminase , Aspartate Aminotransferases , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Female , Hepatitis B Surface Antigens/isolation & purification , Hepatitis B virus/immunology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/virology , Hong Kong/epidemiology , Humans , Male , Medical History Taking/statistics & numerical data , Middle Aged , Retrospective Studies , Risk Assessment/statistics & numerical data , Risk Factors
15.
Open Forum Infect Dis ; 8(6): ofab205, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1261053

ABSTRACT

BACKGROUND: Liver injury in patients with coronavirus disease 2019 (COVID-19) is common and prognostic. Direct viral tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for angiotensin-converting enzyme 2 receptors in hepatocytes may be one of the mechanisms of liver injury. We aimed to determine the role of viral persistence of SARS-CoV-2, based on cycle threshold (Ct) value, in liver injury in COVID-19. METHODS: This was a territory-wide retrospective cohort study of all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 was identified. Serial liver biochemistries and Ct values of SARS-CoV-2 RNA were analyzed. RESULTS: We identified 7622 COVID-19 patients (mean age, 47 years; 48.2% male) diagnosed from March 24 to January 1, 2021, who had serial liver biochemistries and Ct values. A total of 1363 (17.9%) COVID-19 patients had alanine transferase (ALT)/aspartate aminotransferase (AST) elevations with 2 temporal patterns-early (within first 14 days of symptom onset) and late (>14 days from symptom onset). COVID-19 patients with ALT/AST elevations had a lower Ct value at admission (23 vs 25; P < .001), day 5 (24 vs 26; P < .001), and day 20 (31 vs 32; P < .001) after admission, compared with those without ALT/AST elevations. COVID-19 patients with ALT/AST elevations had a longer duration from first positive to first negative reverse transcription polymerase chain reaction test for SARS-CoV-2 (13 vs 9 days; P < .001). ALT/AST elevation and presence of diabetes were independent risk factors of viral persistence. CONCLUSIONS: Liver injury in COVID-19 is linked to a higher SARS-CoV-2 viral load during the early phase of infection, signifying a possible direct viral injury to the liver. Prolonged viral persistence of SARS-CoV-2 is associated with liver injury.

17.
J Am Soc Nephrol ; 2021 Jan 22.
Article in English | MEDLINE | ID: covidwho-1197445

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

18.
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
19.
Gut ; 70(4): 698-706, 2021 04.
Article in English | MEDLINE | ID: covidwho-1024254

ABSTRACT

OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.


Subject(s)
Bacteria , COVID-19 , Dysbiosis , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract , Immunity , SARS-CoV-2 , Adult , Bacteria/genetics , Bacteria/immunology , Bacteria/isolation & purification , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , Cytokines/analysis , DNA, Bacterial/isolation & purification , Dysbiosis/epidemiology , Dysbiosis/etiology , Dysbiosis/immunology , Dysbiosis/virology , Female , Gastrointestinal Tract/immunology , Gastrointestinal Tract/microbiology , Gastrointestinal Tract/virology , Hong Kong , Humans , Male , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferases/analysis
20.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1015001

ABSTRACT

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Subject(s)
COVID-19/metabolism , Immunity, Innate/drug effects , Influenza, Human/metabolism , Interleukins/pharmacology , Pneumonia/prevention & control , Poly I-C/toxicity , Respiratory System/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/metabolism , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Influenza A virus/isolation & purification , Influenza, Human/immunology , Influenza, Human/virology , Interleukin-1/blood , Interleukins/blood , Male , Mice , Mice, Inbred C57BL , Pneumonia/chemically induced , Pneumonia/immunology , Pneumonia/pathology , Respiratory System/metabolism , Respiratory System/pathology , SARS-CoV-2/isolation & purification
SELECTION OF CITATIONS
SEARCH DETAIL