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2.
Front Immunol ; 12: 744696, 2021.
Article in English | MEDLINE | ID: covidwho-1485054

ABSTRACT

Background: Little is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection. Methods: We systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition. Results: 21 studies were included in the primary MA, describing 8,251 admissions across 8 countries during the first wave, comprising 1513 probable or definite nosocomial COVID-19, and 6738 community-acquired cases. Across all studies, the risk of mortality was 1.3 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.005 to 1.683). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61). Conclusions: Adults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups. Systematic Review Registration: PROSPERO CRD42021249023.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Hospitalization , Immunocompromised Host , Inpatients , SARS-CoV-2 , Adult , COVID-19/therapy , Disease-Free Survival , Humans , Risk Factors , Survival Rate
3.
Curr Opin Allergy Clin Immunol ; 21(6): 525-534, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1447630

ABSTRACT

PURPOSE OF REVIEW: The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). RECENT FINDINGS: Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. SUMMARY: In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/genetics , Agammaglobulinemia/complications , COVID-19/immunology , Genetic Diseases, X-Linked/complications , SARS-CoV-2/immunology , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , COVID-19/diagnosis , COVID-19/virology , Evolution, Molecular , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index
4.
Thorax ; 76(12): 1246-1249, 2021 12.
Article in English | MEDLINE | ID: covidwho-1322847

ABSTRACT

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%-35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21-63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures.


Subject(s)
COVID-19 , Cross Infection , Adult , Cross Infection/epidemiology , Hospitals , Humans , Retrospective Studies , SARS-CoV-2 , Wales/epidemiology
5.
Immunology ; 164(1): 135-147, 2021 09.
Article in English | MEDLINE | ID: covidwho-1295026

ABSTRACT

Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalized SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Saliva
6.
J Clin Pathol ; 2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1090886

ABSTRACT

BACKGROUND: The role of specific blood tests to predict poor prognosis in patients admitted with infection from SARS-CoV-2 remains uncertain. During the first wave of the global pandemic, an extended laboratory testing panel was integrated into the local pathway to guide triage and healthcare resource utilisation for emergency admissions. We conducted a retrospective service evaluation to determine the utility of extended tests (D-dimer, ferritin, high-sensitivity troponin I, lactate dehydrogenase and procalcitonin) compared with the core panel (full blood count, urea and electrolytes, liver function tests and C reactive protein). METHODS: Clinical outcomes for adult patients with laboratory-confirmed COVID-19 admitted between 17 March and 30 June 2020 were extracted, alongside costs estimates for individual tests. Prognostic performance was assessed using multivariable logistic regression analysis with 28-day mortality used as the primary endpoint and a composite of 28-day intensive care escalation or mortality for secondary analysis. RESULTS: From 13 500 emergency attendances, we identified 391 unique adults admitted with COVID-19. Of these, 113 died (29%) and 151 (39%) reached the composite endpoint. 'Core' test variables adjusted for age, gender and index of deprivation had a prognostic area under the curve of 0.79 (95% CI 0.67 to 0.91) for mortality and 0.70 (95% CI 0.56 to 0.84) for the composite endpoint. Addition of 'extended' test components did not improve on this. CONCLUSION: Our findings suggest use of the extended laboratory testing panel to risk stratify community-acquired COVID-19 positive patients on admission adds limited prognostic value. We suggest laboratory requesting should be targeted to patients with specific clinical indications.

7.
Ann Clin Biochem ; 58(2): 123-131, 2021 03.
Article in English | MEDLINE | ID: covidwho-1067019

ABSTRACT

BACKGROUND: Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. METHODS: A pathway utilizing a newborn screening laboratory infrastructure was developed using an enzyme-linked immunosorbent assay to detect IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody-positive and -negative subjects and polymerase chain reaction positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. RESULTS: DBS specimens from antibody-negative (n = 85) and -positive (n = 35) subjects and polymerase chain reaction positive subjects (n = 11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y = 0.004041 + 1.005x, r = 0.991, Sy/x 0.171, n = 82. Extraction efficiency of antibodies from DBS specimens was >99%. DBS specimens were stable for at least 28 days at ambient room temperature and humidity. CONCLUSIONS: SARS-CoV-2 IgG receptor-binding domain antibodies can be reliably detected in DBS specimens. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing , COVID-19/immunology , Dried Blood Spot Testing , Immunoglobulin G/immunology , SARS-CoV-2/immunology , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Spike Glycoprotein, Coronavirus/immunology
9.
BMJ ; 371: m4288, 2020 11 11.
Article in English | MEDLINE | ID: covidwho-970809
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