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PMC:7319613 JSONTXT 17 Projects

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Id Subject Object Predicate Lexical cue
T1 0-14 Sentence denotes Preterm birth:
T2 15-67 Sentence denotes Potential risk factor for greater COVID-19 severity?
T3 69-257 Sentence denotes The novel coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major health (& economic) issue across the globe.
T4 258-357 Sentence denotes As of June 20th, more than eight and a half million human infections have been confirmed worldwide.
T5 358-522 Sentence denotes While the exact pathophysiology is still investigated, significant individual variability in the disease severity and subsequent consequences has been demonstrated.
T6 523-828 Sentence denotes The respiratory distress syndrome related to SARS-CoV-2 infection seems highly specific with a desaturation despite sometimes an absence of dyspnea and distinct manifestations like large intrapulmonary shunt or vascular abnormalities such as thrombosis and increased angiogenesis (Ackermann et al., 2020).
T7 829-1125 Sentence denotes Current evidence from large prospective COVID-19 patients cohort studies suggests that the key independent risk factors for mortality and severe complications include higher age, male sex and chronic comorbidities, predominantly related to obesity and metabolic dysfunctions (Liang et al., 2020).
T8 1126-1291 Sentence denotes Fast identification of “more-at-risk” populations is key for optimization of therapy selection and timing, especially when health care system capacities are limited.
T9 1292-1422 Sentence denotes One such, to-date neglected population that is potentially more »vulnerable« to COVID-19 consists of prematurely born individuals.
T10 1423-1611 Sentence denotes Given that preterm birth prevalence is currently estimated at approximately 10 % births worldwide, the potential consequences of prematurity relate to a significant part of the population.
T11 1612-1732 Sentence denotes We argue, that three important features associated with prematurity constitute the basis of such probable vulnerability:
T12 1733-1835 Sentence denotes First, the detrimental long-term consequences on respiratory system development, control and function.
T13 1836-2003 Sentence denotes Second, higher levels of (and possibly reduced tolerance to) oxidative stress and third, potentially elevated Angiotensin-converting enzyme (ACE2) activity/expression.
T14 2004-2143 Sentence denotes Prematurity can provoke life-long adverse sequelae in numerous physiological systems but might predominantly affect the respiratory system.
T15 2144-2291 Sentence denotes Importantly, recent accumulating evidence suggests that the respiratory drive/control might be particularly compromised under hypoxemic conditions.
T16 2292-2537 Sentence denotes Indeed, it is well established that the ventilatory response to hypoxic stimuli is blunted in prematurely born individuals as compared to their full-term born and physical capacity matched counterparts (Bates et al., 2014; Debevec et al., 2019).
T17 2538-2754 Sentence denotes Whilst the exact mechanisms of prematurity-related altered resting cardiorespiratory control and carotid chemoreceptor dysfunction remain unknown, perinatal hyperoxia was hypothesized to be the key underlying factor.
T18 2755-2882 Sentence denotes Other anatomical and functional consequences of prematurity might even further exacerbate the observed respiratory dysfunction.
T19 2883-2966 Sentence denotes The reduced ventilatory response to hypoxia may lead to greater systemic hypoxemia.
T20 2967-3046 Sentence denotes This can be particularly problematic in already hypoxemic clinical populations.
T21 3047-3283 Sentence denotes Hypoxemia is a defining feature of COVID-19 that is independently associated with in-hospital mortality (Xie et al., 2020) and might importantly underline the disease-related respiratory challenges and end-point outcomes in this cohort.
T22 3284-3623 Sentence denotes Whilst other factors associated with COVID-19 also importantly modulate the ventilatory drive (i.e., higher metabolic drive related to fever & inflammation) the potentially blunted hypoxic ventilatory response and subsequently greater systemic hypoxemia in prematurely born individuals should be considered when managing COVID-19 patients.
T23 3624-3856 Sentence denotes Recently, it has been speculated that the hypoxemia and associated pulmonary pathology observed in COVID-19 patients may arise from a reduced oxygen-sensing capacity in pulmonary arteries and in carotid bodies (Archer et al., 2020).
T24 3857-4061 Sentence denotes The resulting dysfunctional regulation of ventilation may be particularly deleterious in combination with pre-existing deficits of the ventilatory response, as is the case in prematurely born individuals.
T25 4062-4170 Sentence denotes It is well established that oxygen sensing in the lung and carotid bodies depends on mitochondrial function.
T26 4171-4474 Sentence denotes The known vulnerability of mitochondria to oxidative stress suggests an additional feature of prematurity to be relevant for impaired oxygen sensing and COVID-19 severity; potentially higher oxidative stress levels as compared to full-term born individuals (Filippone et al., 2012; Martin et al., 2018).
T27 4475-4649 Sentence denotes This difference in redox balance has indeed been hypothesized to be directly involved in the modulation of the ventilatory response to hypoxaemia in prematurely born persons.
T28 4650-4777 Sentence denotes Inflammation related to COVID-19 further increases oxidative stress, while oxidative stress, in turn, can promote inflammation.
T29 4778-4892 Sentence denotes A basal redox regulation deficit thus might increase the risk to get trapped in this detrimental feedforward loop.
T30 4893-4998 Sentence denotes Oxidative stress furthermore leads to oxidized phospholipids, commonly present in COVID-19 patient lungs.
T31 4999-5172 Sentence denotes Oxidized phospholipids have been linked to coagulation abnormalities and low platelet counts, which are associated with adverse outcome of COVID-19 (Merad and Martin, 2020).
T32 5173-5388 Sentence denotes Given that COVID-19 risk factors/conditions are commonly characterized by high oxidative stress levels it seems plausible that redox balance deficits are among the underlying mechanisms of vulnerability to COVID-19.
T33 5389-5532 Sentence denotes Therefore, the potentially altered oxidative stress status linked to prematurity must be considered as it might exacerbate the clinical status.
T34 5533-5681 Sentence denotes Finally, accumulating evidence indicates that prematurity might also be associated with higher ACE2 activity and/or expression (South et al., 2018).
T35 5682-5850 Sentence denotes ACE-2 is known to be directly involved in SARS-CoV-2 cell-binding, representing the main host cell receptor for all human pathogenic coronaviruses including SARS-CoV-2.
T36 5851-5971 Sentence denotes Thus, the higher ACE2 activity/expression in the prematurely born individuals might result in greater COVID-19 severity.
T37 5972-6236 Sentence denotes One also has to bear in mind that the prematurity-related higher ACE2 activity might be additionally heightened by potential hypertension or diabetes drug therapies which often include ACE inhibitors and/or angiotensin II receptor blockers, both upregulating ACE2.
T38 6237-6355 Sentence denotes In summary, prematurely born COVID-19 patients could be particularly vulnerable to both infection and adverse outcome.
T39 6356-6448 Sentence denotes High ACE2 activity levels may enable enhanced virus-binding, thus increasing infection risk.
T40 6449-6669 Sentence denotes A pre-existing adverse redox balance could then contribute to the aggravation of inflammatory mechanisms by oxidation of different biomolecules including phospholipids, incidentally exacerbating vascular and lung injury.
T41 6670-6966 Sentence denotes Oxidative damage to oxygen-sensing mitochondria in conjunction with COVID-19-related hypoxemia and prematurity-associated ventilator response deficits may synergistically deteriorate the health status facilitated by a potentially compromised respiratory system of the prematurely born individual.
T42 6967-7127 Sentence denotes We believe that the above-summarized data and mechanisms observed in prematurely born individuals should be considered when managing/treating COVID-19 patients.
T43 7128-7420 Sentence denotes As no sound epidemiological data currently exist on the topic, future epidemiological and experimental efforts are urgently warranted to elucidate the relationship between prematurity and COVID-19 severity and thereby optimize therapeutic approaches for this, up-to-now neglected, population.
T44 7422-7451 Sentence denotes Author contribution statement
T45 7452-7521 Sentence denotes All authors contributed to the preparation and writing of the Letter.
T46 7522-7588 Sentence denotes All authors read and approved the final version of the manuscript.
T47 7590-7623 Sentence denotes Declaration of Competing Interest
T48 7624-7705 Sentence denotes The authors declare no conflicts of interest related to the topic of this Letter.