LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T155 0-4 Sentence denotes 4.3.
T156 5-64 Sentence denotes Possible Reasons for Methemoglobinemia in COVID-19 Patients
T157 65-195 Sentence denotes There are several factors relevant to explain why methemoglobinemia and carboxyhemoglobinemia can be present in COVID-19 patients.
T158 196-302 Sentence denotes The SARS-CoV-2 infection, the individual constitution and the medical treatment seem to be the major ones.
T159 303-418 Sentence denotes It is well known that several medical drugs can increase MetHb concentration in the blood as a side-effect [26,27].
T160 419-551 Sentence denotes A recent review reports the early recognition, pathophysiology, and management of methemoglobinemia in the intensive care unit [28].
T161 552-677 Sentence denotes Chloroquine is such a drug for which reports were published regarding induced methemoglobinemia due to its intake [29,30,31].
T162 678-873 Sentence denotes Both chloroquine and hydroxychloroquine (a derivative of chloroquine) are currently used to treat COVID-19, while debate is ongoing about their effectiveness and safety [32,33,34,35,36,37,38,39].
T163 874-1081 Sentence denotes Moderately certain evidence suggests that hydroxychloroquine lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or at risk of hospitalization in outpatients with COVID-19.
T164 1082-1209 Sentence denotes A G6PD deficiency can enhance the probability of methemoglobinemia induced by oxidizing drugs, such as hydroxychloroquine [40].
T165 1210-1452 Sentence denotes However, a very recent experimental animal study suggests that short-course high doses of hydroxychloroquine do not induce methemoglobinemia or clinically significant hemolytic anemia or organ damage in a murine model of G6PD deficiency [41].
T166 1453-1535 Sentence denotes Clinically, chronic hemolytic anemia associated with G6PD deficiency is rare [42].
T167 1536-1668 Sentence denotes So far, no evidence of hemolysis was observed in patients with G6PD deficiency when exposed to low doses of hydroxychloroquine [43].
T168 1669-1841 Sentence denotes The first case of severe hemolytic crisis was found in a seriously ill COVID-19 patient with G6PD deficiency following treatment with high doses of hydroxychloroquine [44].
T169 1842-1915 Sentence denotes Several other cases have subsequently been reported by others [45,46,47].
T170 1916-2156 Sentence denotes Nevertheless, Mastroianni et al. [47] and Afra [48], concerning hydroxychloroquine use in G6PD-deficient patients, have indicated that it is difficult to assess the relationship between hydroxychloroquine and hemolysis in COVID-19 patients.
T171 2157-2379 Sentence denotes With the global spread of COVID-19, especially in regions with a high prevalence of G6PD deficiency, these cases should alert physicians to the possible correlation between G6PD-deficiency and hydroxychloroquine treatment.
T172 2380-2502 Sentence denotes In the reports on MetHb and COVID-19 summarized in Section 3.2, the use of chloroquine or hydroxychloroquine is described.
T173 2503-2881 Sentence denotes In the case reported by Kuipers et al. [17], the subject received chloroquine and had a G6PD deficiency; hydroxychloroquine was administered to the subject reported by Faisal et al. [20] (the G6PD status was not reported); and in the three cases reported by Naymagon et al. [18] all received hydroxychloroquine, while one subject was tested for G6PD deficiency and was positive.
T174 2882-3084 Sentence denotes In the cases reported by Al-Aamri et al. [23] and Palmer et al. [22], the patients did not receive chloroquine and hydroxychloroquine, but the patient described by Al-Aamri et al. had a G6PD deficiency.
T175 3085-3279 Sentence denotes A G6PD deficiency is not only relevant with respect to the reaction to antiviral oxidizing drugs, but also for the effects of the drug methylene blue administered to treat the methemoglobinemia.
T176 3280-3488 Sentence denotes Methylene blue may be ineffective in patients with a G6PD deficiency since they lack sufficient reduced nicotinamide adenine dinucleotide phosphate (NADPH) to reduce methylene blue to leuko-methylene [49,50].
T177 3489-3720 Sentence denotes Despite the obvious effect of oxidizing drugs on the formation of MetHb, it can also be formed as a byproduct of a physiological reaction in the form of an adaptive increased nitric oxide (NO) signaling due to an acute anemia [51].
T178 3721-3899 Sentence denotes Anemia can be associated with an infection and/or a systemic inflammatory reaction, termed “anemia of inflammation”, as part of the physiological reaction to the disease [52,53].
T179 3900-4092 Sentence denotes According to a study by Bellmann-Weiler et al. [54] on 259 hospitalized patients with COVID-19, 24.7% were anemic on admission, with the majority suffering from anemia of inflammation (68.8%).
T180 4093-4190 Sentence denotes During hospitalization, the percentage of patients with anemia increased (around 68.8% at day 7).
T181 4191-4298 Sentence denotes A significantly higher mortality during hospitalization was also found in those with anemia upon admission.
T182 4299-4479 Sentence denotes Anemia is associated with an increased NO expression, leading to vasodilation and thus preventing tissue hypoxia, but also causing increased NO-based oxidation of Hb to MetHb [51].
T183 4480-4583 Sentence denotes Interestingly, anemia, and drops in total Hb (tHb), have been reported in COVID-19 patients [22,55,56].
T184 4584-4795 Sentence denotes An anticorrelated development of tHb levels and MetHb levels in a COVID-19 patient has been reported [22], in line with the pathway described by Hare et al. [51] of an NO-induced MetHb increase caused by anemia.
T185 4796-4953 Sentence denotes The role of MetHb as a marker of anemic stress has been also been validated in a study investigating MetHb changes in patients undergoing heart surgery [57].
T186 4954-5160 Sentence denotes While “anemia of inflammation” is associated with methemoglobinemia, iron-deficient anemia seems to be a further risk factor for acquired methemoglobinemia by enhancing red blood cell oxidative stress [58].
T187 5161-5282 Sentence denotes The occurrence of methemoglobinemia due to a viral infection has been reported for several types of infection [59,60,61].
T188 5283-5454 Sentence denotes For example, the activity of MetHb reductase has been shown to be negatively affected by infections with Plasmodium yoelii nigeriensis [62,63] or Plasmodium knowlesi [61].
T189 5455-5796 Sentence denotes The fact that the severity of the methemoglobinemia observed in COVID-19 patients was dependent on the subject firstly reflects the different disease severities of the patients but is also most probably due to the physiological constitution of the subjects before the disease, related to their medical history, their overall fitness and age.
T190 5797-5987 Sentence denotes The age factor seems to be of particular interest since, for example, erythrocytes from elderly humans are more easily affected by oxidative stress, facilitating the formation of MetHb [64].
T191 5988-6030 Sentence denotes MetHb can have proinflammatory properties.
T192 6031-6165 Sentence denotes For example, it activates the NF-κB pathway in endothelial cells associated with chemokine (IL-8) and cytokine (IL-6) production [65].
T193 6166-6386 Sentence denotes The activation of the NF-κB and MAPK pathways with subsequent release of the chemokines IL-8 and the chemokine monocyte chemoattractant protein-1 (MCP-1) has also been observed in endothelial cells exposed to MetHb [66].
T194 6387-6638 Sentence denotes This underlines that an elevation of MetHb in the blood has an effect on cytokine/chemokine production—a fact that might be of particular relevance for COVID-19 since a “cytokine storm” has been observed in severe courses of the disease [67,68,69,70].
T195 6639-6782 Sentence denotes At the same time, it must also be borne in mind that hypoxia also causes the production of cytokines and cytokines, like IL-8 and IL-6 [71,72].