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1.
Public Health ; 209: 46-51, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1946325

ABSTRACT

OBJECTIVES: Healthcare worker (HCW) SARS-CoV-2 contacts in England have been required to quarantine, creating staff shortages. We piloted daily contact testing (DCT) to assess its feasibility as an alternative. STUDY DESIGN: Observational service evaluation. METHODS: We conducted an observational service evaluation of 7-day DCT using antigen lateral flow devices (LFDs) at four acute hospital trusts and one ambulance trust in England. Mixed methods were used, using aggregate and individual-level test monitoring data, semi-structured interviews, and a survey of eligible contacts. RESULTS: In total, 138 HCWs were identified as contacts of a confirmed SARS-CoV-2 case. Of these, 111 (80%) consented to daily LFD testing, of whom 82 (74%) completed the required programme without interruption and 12 (11%) completed with interruption. Fifty-eight participants (52%) and two non-participants (7.4%) completed the survey. In total, 28 interviews were conducted with participants, site and infection control leads, and union representatives. One participant tested positive on LFD and polymerase chain reaction (PCR) test. Three participants tested positive on PCR but not LFD. DCT was well-accepted by trusts and staff. Participants reported no relaxation of their infection prevention and control behaviours. No incidents of transmission were detected. An estimated 729 potential days of work absence were averted. CONCLUSIONS: DCT can be acceptably operated in a healthcare setting, averting quarantine-related work absences in HCW SARS-CoV-2 contacts.


Subject(s)
COVID-19 , SARS-CoV-2 , Ambulances , COVID-19/diagnosis , England , Hospitals , Humans
2.
J Med Entomol ; 59(4): 1479-1483, 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1873941

ABSTRACT

Flies and other arthropods mechanically transmit multiple pathogens and a recent experimental study demonstrated house flies, Musca domestica L. (Diptera: Muscidae), can mechanically transmit SARS-CoV-2. The purpose of this study was to explore the possibility of mechanical transmission of SARS-CoV-2 by domestic insects and their potential as a xenosurveillance tool for detection of the virus. Flies were trapped in homes where at least one confirmed human COVID-19 case(s) resided using sticky and liquid-baited fly traps placed inside and outside the home in the Texas counties of Brazos, Bell, and Montgomery, from June to September 2020. Flies from sticky traps were identified, pooled by taxa, homogenized, and tested for the presence of SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR). Liquid traps were drained, and the collected fluid similarly tested after RNA concentration. We processed the contents of 133 insect traps from 40 homes, which contained over 1,345 individual insects of 11 different Diptera families and Blattodea. These individuals were grouped into 243 pools, and all tested negative for SARS-CoV-2 RNA. Fourteen traps in seven homes were deployed on the day that cat or dog samples tested positive for SARS-CoV-2 RNA by nasal, oral, body, or rectal samples. This study presents evidence that biting and nonbiting flies and cockroaches (Blattodea) are not likely to contribute to mechanical transmission of SARS-CoV-2 or be useful in xenosurveillance for SARS-CoV-2.


Subject(s)
COVID-19 , Cockroaches , Dog Diseases , Houseflies , Muscidae , Animals , Dogs , Humans , Insect Control , RNA, Viral , SARS-CoV-2
4.
Emerg Infect Dis ; 28(2): 440-444, 2022 02.
Article in English | MEDLINE | ID: covidwho-1650669

ABSTRACT

Inhabitants of the Greater Mekong Subregion in Cambodia are exposed to pathogens that might influence serologic cross-reactivity with severe acute respiratory syndrome coronavirus 2. A prepandemic serosurvey of 528 malaria-infected persons demonstrated higher-than-expected positivity of nonneutralizing IgG to spike and receptor-binding domain antigens. These findings could affect interpretation of large-scale serosurveys.


Subject(s)
COVID-19 , Malaria , Antibodies, Viral , Cambodia/epidemiology , Humans , Malaria/epidemiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Clin Radiol ; 77(2): 148-155, 2022 02.
Article in English | MEDLINE | ID: covidwho-1611681

ABSTRACT

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.


Subject(s)
COVID-19/diagnostic imaging , Computed Tomography Angiography , SARS-CoV-2/genetics , Severity of Illness Index , Whole Genome Sequencing , Aged , COVID-19/mortality , COVID-19/virology , Cohort Studies , Critical Care , Female , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Time Factors , United Kingdom , Viral Load
7.
Sci Transl Med ; 13(620): eabj7790, 2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1467665

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.


Subject(s)
COVID-19 , Cellular Senescence , Fibrinolysis , Humans , Lung , SARS-CoV-2
8.
Antimicrobial Resistance and Infection Control ; 10(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1448382

ABSTRACT

Introduction: A better understanding of the relative importance of different transmission pathways of SARS-CoV-2 in hospital settings has the potential to help improve targeting of control measures aimed at reducing nosocomial spread. Objectives: To quantify the associations between risks of nosocomial SARS-CoV-2 infection and exposure on the same ward to infected healthcare workers (HCWs), to patients likely to have been infected nosocomially, and to patients with community onset COVID-19. Methods: Ward-level data were collected from four teaching hospitals in Oxfordshire, UK, over an 8 month period in 2020. SARS-CoV-2 infections were identified using both PCR results from symptomatic and asymptomatic testing and serological data coupled with symptom recall. A series of statistical models were used to quantify associations between exposures and probable hospital transmission events. Results: Risk to patients of probable nosocomial acquisition was most strongly associated with exposure to other patients with hospitalacquired SARS-CoV-2 (aOR, 1.76, 95%CI 1.51, 2.04), followed by the presence of an infected HCW on the same ward (aOR 1.45, 95%CI 1.22,1.71). The association with patients with community onset COVID- 19 was weaker (aOR 1.12, 95%CI 0.96,1.26). Transmission to HCWs was associated with exposure to other infectious HCWs and patients with hospital-acquired SARS-CoV-2 (aOR 1.66, 95%CI 1.55,1.78 and aOR 1.45, 95%CI 1.32,1.58 respectively). The introduction of more stringent infection prevention and control measures which included testing all patients for SARS-CoV-2 by PCR on admission and at weekly intervals was associated with substantial reduction in transmission risk to both patients (adjusted odds ratio, aOR 0.25, 95%CI 0.14, 0.42) and HCWs (aOR 0.43, 95%CI 0.34, 0.53). Conclusion: Patients who acquired SARS-CoV-2 in the hospital and, to a lesser degree, infectious HCWs likely working prior to the onset of symptoms, were the most strongly associated with increased risk of SARSCoV- 2 transmission. In contrast, exposure to patients who had acquired SARS-CoV-2 in the community was associated with, at most, modest increases in the daily risk of infection for both healthcare staff and the other patients.

10.
Am J Public Health ; 111(7): 1267-1272, 2021 07.
Article in English | MEDLINE | ID: covidwho-1350205

ABSTRACT

Both the 1918 influenza pandemic and the 2019‒2021 COVID-19 pandemic are among the most disastrous infectious disease emergences of modern times. In addition to similarities in their clinical, pathological, and epidemiological features, the two pandemics, separated by more than a century, were each met with essentially the same, or very similar, public health responses, and elicited research efforts to control them with vaccines, therapeutics, and other medical approaches. Both pandemics had lasting, if at times invisible, psychosocial effects related to loss and hardship. In considering these two deadly pandemics, we ask: what lessons have we learned over the span of a century, and how are we applying those lessons to the challenges of COVID-19?


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/organization & administration , Influenza, Human/epidemiology , Pandemics/history , COVID-19/history , COVID-19/pathology , History, 20th Century , History, 21st Century , Humans , Influenza, Human/history , Public Health/history
11.
Sci Transl Med ; 13(601)2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301563
12.
Am J Public Health ; 111(6): 1086-1094, 2021 06.
Article in English | MEDLINE | ID: covidwho-1217009

ABSTRACT

Separated by a century, the influenza pandemic of 1918 and the COVID-19 pandemic of 2019-2021 are among the most disastrous infectious disease emergences of modern times. Although caused by unrelated viruses, the two pandemics are nevertheless similar in their clinical, pathological, and epidemiological features, and in the civic, public health, and medical responses to combat them. Comparing and contrasting the two pandemics, we consider what lessons we have learned over the span of a century and how we are applying those lessons to the challenges of COVID-19.


Subject(s)
COVID-19/epidemiology , Influenza, Human/epidemiology , Pandemics/history , SARS-CoV-2/isolation & purification , COVID-19/history , COVID-19/pathology , History, 20th Century , History, 21st Century , Humans , Influenza A virus/isolation & purification , Influenza, Human/history , Influenza, Human/pathology , Public Health
13.
Nat Immunol ; 22(1): 67-73, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065904

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Immunoglobulin G/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , COVID-19/metabolism , COVID-19/virology , Child , Cytokines/metabolism , Female , Glycosylation , Humans , Immunoglobulin G/metabolism , Interleukin-6 , Male , Middle Aged , Receptors, IgG/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Severity of Illness Index , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
14.
Am J Trop Med Hyg ; 103(3): 955-959, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-671152

ABSTRACT

The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a ß-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. The risk of similar coronavirus outbreaks in the future remains high. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , COVID-19 , Chiroptera/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Public Health , SARS-CoV-2
15.
Histopathology ; 77(6): 915-925, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-625485

ABSTRACT

INTRODUCTION: We describe post-mortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalisation. METHODS AND RESULTS: Histopathologic findings in post-mortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to detect virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organising phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organising DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium- and large-calibre vessels, platelet microthrombi detected by CD61 IHC and fibrin microthrombi. CONCLUSIONS: Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute, but not in the organising phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organising phase the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Adult , Aged , Autopsy , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , Humans , Immunohistochemistry , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , RNA, Viral , SARS-CoV-2
16.
mBio ; 11(3)2020 05 29.
Article in English | MEDLINE | ID: covidwho-428675

ABSTRACT

With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history. Some have killed sizeable percentages of humanity, but humans have always searched for, and often found, ways of mitigating their deadly effects. We here review the ancient and modern histories of such diseases, discuss factors associated with their emergences, and attempt to identify lessons that will help us meet the current challenge.


Subject(s)
Coronavirus Infections/epidemiology , Pandemics/history , Pneumonia, Viral/epidemiology , Animals , Betacoronavirus/pathogenicity , COVID-19 , Communicable Disease Control/history , Conservation of Natural Resources , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , History, Ancient , History, Medieval , Humans , International Cooperation , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Public Health/history , SARS-CoV-2 , Zoonoses/epidemiology , Zoonoses/prevention & control , Zoonoses/transmission
17.
Preprint in English | medRxiv | ID: ppmedrxiv-20103341

ABSTRACT

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a public health crisis that is exacerbated by our poor understanding of correlates of immunity. SARS-CoV-2 infection can cause Coronavirus Disease 2019 (COVID-19), with a spectrum of symptoms ranging from asymptomatic carriage to life threatening pneumonia and cytokine dysregulation [1-3]. Although antibodies have been shown in a variety of in vitro assays to promote coronavirus infections through mechanisms requiring interactions between IgG antibodies and Fc gamma receptors (Fc{gamma}Rs), the relevance of these observations to coronavirus infections in humans is not known [4-7]. In light of ongoing clinical trials examining convalescent serum therapy for COVID-19 patients and expedited SARS-CoV-2 vaccine testing in humans, it is essential to clarify the role of antibodies in the pathogenesis of COVID-19. Here we show that adults with PCR-diagnosed COVID-19 produce IgG antibodies with a specific Fc domain repertoire that is characterized by reduced fucosylation, a modification that enhances interactions with the activating Fc{gamma}R, Fc{gamma}RIIIa. Fc fucosylation was reduced when compared with SARS-CoV-2-seropositive children and relative to adults with symptomatic influenza virus infections. These results demonstrate an antibody correlate of symptomatic SARS-CoV-2 infections in adults and have implications for novel therapeutic strategies targeting Fc{gamma}RIIIa pathways.

18.
Journal of Clinical Microbiology ; 58(1):e00963, 2020.
Article | WHO COVID | ID: covidwho-17602

ABSTRACT

Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 102 to 103 genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P=4.7×10-5). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [CT] values, <30) and 6/13 samples with low viral titers (CT values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.

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