Global outbreak research: harmony not hegemony

Akhvlediani, Tamar; Ali, Syed Mansoor; Angus, Derek C.; Arabi, Yaseen M.; Sheharyar, Ashraf; Baillie, J Kenneth; Bakamutumaho, Barnabas; Beane, Abi; Bozza, Fernando A.; Brett, Stephen; Bruzzone, Roberto; Carson, Gail; Castle, Lyndsey; Christian, Michael D.; Cobb, J Perren; Cummings, Matthew J.; D’Ortenzio, Éric; Jong, Menno D. de; Denis, Emmanuelle; Derde, Lennie; Dobell, Emily; Dondorp, Arjen M.; Dunning, Jake; Everett, Dean; Farrar, Jeremy; Fowler, Rob; Gamage, Dilanthi; Gao, Zhancheng; Gomersall, Charles D; Gordon, Anthony; Haniffa, Rashan; Hardwick, Hayley; Hashmi, Madiha; Hayat, Mohammad; Hayden, Frederick G.; Ho, Antonia; Horby, Peter; Jamieson, Nina; Jawad, Issrah; Kennon, Kalynn; Khaskheli, Saleh; Khoo, Saye; Lang, Trudie; Lee, James; Ling, Lowell; John, Marshall; Memon, Mohammad I; Merson, Laura; Moore, Sarah R.; Murthy, Srinivas; Nichol, Alistair; O’Donnell, Max R; Olliaro, Piero; Openshaw, Peter; Parke, Rachael; Pereira, Rui; Plotkin, Daniel; Pritchard, Mark G; Rabindrarajan, Ebenezer; Ramakrishnan, Nagarajan; Richards, Toby; Ruíz-Palacios, Guillermo M.; Russell, Clark D; Scott, Janet T.; Semple, Malcolm G; Shindo, Nahoko; Sigfrid, Louise; Somers, Emily C.; Taqi, Arshad; Turtle, Lance; Thevarajan, Irani; Vijayaraghavan, Bharath Kumar Tirupakuzhi; Udayanga, Ishara; Werf, Sylvie van der; Vatrinet, Renaud; Vecham, Pavan Kumar; Webb, Steve; Amuasi, John; Çevik, Müge; Fischer, William A.; Fletcher, Tom

doi:10.1016/s1473-3099(20)30440-0

Cited by 41 publications

(28 citation statements)

References 9 publications

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“…All clinical information was prospectively collected using a standardized form: International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)/World Health Organization (WHO) Clinical Characterization Protocol for Severe Emerging Infections (CCP-BR). 39 Clinical and laboratory data were recorded on admission in all severe patients included in the study, and the primary outcome analyzed was 28-day mortality (n = 18 survivors and 17 nonsurvivors; supplemental Table 2). Age and the frequency of comorbidities were not different between severe patients requiring mechanical ventilation or noninvasive oxygen supplementation or between survivors and nonsurvivors (supplemental Tables 1 and 2).…”

Section: Methodsmentioning

confidence: 99%

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Hottz

Azevedo-Quintanilha

Palhinha

et al. 2020

Blood

655

754

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregate formation are observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.

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Section: Methodsmentioning

confidence: 99%

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Hottz

Azevedo-Quintanilha

Palhinha

et al. 2020

Blood

655

754

View full text Add to dashboard Cite

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“…Demographic, clinical, and biological data were collected by trained investigators using the standardized form International Severe Acute Respiratory and Emerging Infection Consortium/World Health Organization Clinical Characterization Protocol (ISARIC/WHO CCP) [ 10 ]. Data were entered in electronic case-report forms at Research Electronic Data Capture (REDCap, https://projectredcap.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Liver injury predicts overall mortality in severe COVID-19: a prospective multicenter study in Brazil

et al. 2021

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Background/purpose The relationship between liver injury and mortality remains unclear in patients with COVID-19. We aimed to evaluate the prognostic value of aminotransferases levels at hospital admission to predict mortality in patients with COVID-19. Methods and results This prospective study included 406 patients [57% male, aged 56 years] with COVID-19 hospitalized in 26 centers in Brazil. Overall, 36.7% (95% CI 32.1–41.5) presented at admission with severe disease requiring respiratory support. The prevalence of elevated ALT and AST levels at admission [> 2 × ULN] was 14.0% (95% CI 11.0–17.8) and 12.9% (95% CI 10.0–16.6), respectively. Sixty-two patients [15.3% (95% CI 12.1–19.1)] died during hospitalization and the overall mortality rate was 13.4 (10.5–17.2) deaths per 1000 persons-years. The 15-day-overall survival (95% CI) was significantly lower in patients with ALT levels ≥ 2 × ULN compared to those with ALT < 2 × ULN [67.1% (48.4–80.2) vs 83.4% (76.1–88.6), p = 0.001] and in those with AST levels ≥ 2 × ULN compared to those with AST < 2 × ULN [61.5% (44.7–74.6) vs 84.2% (76.5–89.5), p < 0.001]. The presence of elevated aminotransferases levels at hospital admission significantly increased the risk of in-hospital all-cause mortality adjusted for age-and-sex. Those findings were present in the subgroup of critically ill patients already admitted in need of respiratory support ( n = 149), but not in patients without that requirement at admission ( n = 257). Conclusions Elevated aminotransferases at hospital admission predicted in-hospital all-cause mortality in patients with COVID-19, especially in those with severe disease. Measurement of transaminases levels at hospital admission should be integrated to the care of patients with COVID-19 as an auxiliary strategy to identify patients at higher death risk. Supplementary Information The online version contains supplementary material available at 10.1007/s12072-021-10141-6.

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“…The study builds on an international consensus protocol for investigation of new infectious diseases, the International Severe Acute Respiratory Infection Consortium/World Health Organisation Clinical Characterisation Protocol (ISARIC/WHO CCP), 20 designed to enable internationallyharmonised clinical research during outbreaks. 21 The protocol, revision history, case report form, information leaflets, consent forms, and details of the Independent Data and Material Access Committee are available at https://isaric4c.net. The UK study was approved by the South Central -Oxford C Research Ethics Committee (13/SC/0149) and by the Scotland A Research Ethics Committee (20/SS/0028).…”

Section: Study Design Setting and Populationmentioning

confidence: 99%

Robust, reproducible clinical patterns in hospitalised patients with COVID-19

Millar

Neyton

Seth

et al. 2020

Preprint

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Severe COVID-19 is characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. The clinical associations of different patterns of symptoms can influence diagnostic and therapeutic decision-making: for example, significant differential therapeutic effects in sub-groups of patients with different severities of respiratory failure have already been reported for the only treatment so far shown to reduce mortality in COVID-19, dexamethasone. We obtained structured clinical data on 68914 patients in the UK (the ISARIC Coronavirus Clinical Characterisation Consortium, 4C) and used a principled, unsupervised clustering approach to partition the first 33468 cases according to symptoms reported at recruitment. We validated our findings in a second group of 35446 cases recruited to ISARIC-4C, and in separate cohort of community cases. A core symptom set of fever, cough, and dyspnoea co-occurred with additional symptoms in three patterns: fatigue and confusion, diarrhoea and vomiting, or productive cough. Presentations with a single reported symptom of dyspnoea or confusion were common, and a subgroup of patients reported few or no symptoms. Patients presenting with gastrointestinal symptoms were more commonly female, had a longer duration of symptoms before presentation, and had lower 30-day mortality. Patients presenting with confusion, with or without core symptoms, were older and had a higher unadjusted mortality. Symptom clusters were highly consistent in replication analysis using a further 35446 individuals subsequently recruited to ISARIC-4C. Similar patterns were externally verified in 4445 patients from a study of self-reported symptoms of mild disease. The large scale of ISARIC-4C study enabled robust, granular discovery and replication of patient clusters. Clinical interpretation is necessary to determine which of these observations have practical utility. We propose that four patterns are usefully distinct from the core symptom groups: gastro-intestinal disease, productive cough, confusion, and pauci-symptomatic presentations. Importantly, each is associated with an in-hospital mortality which differs from that of patients with core symptoms. These observations deepen our understanding of COVID-19 and will influence clinical diagnosis, risk prediction, and future mechanistic and clinical studies.

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Global outbreak research: harmony not hegemony

Cited by 41 publications

References 9 publications

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Liver injury predicts overall mortality in severe COVID-19: a prospective multicenter study in Brazil

Robust, reproducible clinical patterns in hospitalised patients with COVID-19

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