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PMC:7795966 / 19509-26291 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
658 26-43 Disease denotes Methemoglobinemia MESH:D008708
659 47-55 Disease denotes COVID-19 MESH:C000657245
665 186-194 Species denotes patients Tax:9606
666 115-132 Disease denotes methemoglobinemia MESH:D008708
667 137-158 Disease denotes carboxyhemoglobinemia
668 177-185 Disease denotes COVID-19 MESH:C000657245
669 200-220 Disease denotes SARS-CoV-2 infection MESH:C000657245
683 360-365 Gene denotes MetHb Gene:3048
684 986-994 Species denotes patients Tax:9606
685 552-563 Chemical denotes Chloroquine MESH:D002738
686 683-694 Chemical denotes chloroquine MESH:D002738
687 699-717 Chemical denotes hydroxychloroquine MESH:D006886
688 735-746 Chemical denotes chloroquine MESH:D002738
689 916-934 Chemical denotes hydroxychloroquine MESH:D006886
690 501-518 Disease denotes methemoglobinemia MESH:D008708
691 630-647 Disease denotes methemoglobinemia MESH:D008708
692 776-784 Disease denotes COVID-19 MESH:C000657245
693 973-982 Disease denotes mortality MESH:D003643
694 1013-1021 Disease denotes COVID-19 MESH:C000657245
695 1072-1080 Disease denotes COVID-19 MESH:C000657245
724 1415-1421 Species denotes murine Tax:10090
725 1585-1593 Species denotes patients Tax:9606
726 1749-1756 Species denotes patient Tax:9606
727 2021-2029 Species denotes patients Tax:9606
728 2147-2155 Species denotes patients Tax:9606
729 1185-1203 Chemical denotes hydroxychloroquine MESH:D006886
730 1300-1318 Chemical denotes hydroxychloroquine MESH:D006886
731 1644-1662 Chemical denotes hydroxychloroquine MESH:D006886
732 1817-1835 Chemical denotes hydroxychloroquine MESH:D006886
733 1980-1998 Chemical denotes hydroxychloroquine MESH:D006886
734 2102-2120 Chemical denotes hydroxychloroquine MESH:D006886
735 2350-2368 Chemical denotes hydroxychloroquine MESH:D006886
736 1084-1099 Disease denotes G6PD deficiency MESH:D005955
737 1131-1148 Disease denotes methemoglobinemia MESH:D008708
738 1333-1350 Disease denotes methemoglobinemia MESH:D008708
739 1397-1409 Disease denotes organ damage MESH:D019965
740 1431-1446 Disease denotes G6PD deficiency MESH:D005955
741 1506-1521 Disease denotes G6PD deficiency MESH:D005955
742 1559-1568 Disease denotes hemolysis MESH:D006461
743 1599-1614 Disease denotes G6PD deficiency MESH:D005955
744 1740-1748 Disease denotes COVID-19 MESH:C000657245
745 1762-1777 Disease denotes G6PD deficiency MESH:D005955
746 2006-2020 Disease denotes G6PD-deficient MESH:D005955
747 2125-2134 Disease denotes hemolysis MESH:D006461
748 2138-2146 Disease denotes COVID-19 MESH:C000657245
749 2183-2191 Disease denotes COVID-19 MESH:C000657245
750 2241-2256 Disease denotes G6PD deficiency MESH:D005955
751 2330-2345 Disease denotes G6PD-deficiency MESH:D005955
777 2695-2699 Gene denotes G6PD Gene:2539
778 2398-2403 Gene denotes MetHb Gene:3048
779 2956-2964 Species denotes patients Tax:9606
780 3025-3032 Species denotes patient Tax:9606
781 3317-3325 Species denotes patients Tax:9606
782 2455-2466 Chemical denotes chloroquine MESH:D002738
783 2470-2488 Chemical denotes hydroxychloroquine MESH:D006886
784 2569-2580 Chemical denotes chloroquine MESH:D002738
785 2608-2626 Chemical denotes hydroxychloroquine MESH:D006886
786 2795-2813 Chemical denotes hydroxychloroquine MESH:D006886
787 2981-2992 Chemical denotes chloroquine MESH:D002738
788 2997-3015 Chemical denotes hydroxychloroquine MESH:D006886
789 3220-3234 Chemical denotes methylene blue MESH:D008751
790 3280-3294 Chemical denotes Methylene blue MESH:D008751
791 3384-3427 Chemical denotes nicotinamide adenine dinucleotide phosphate MESH:D009249
792 3429-3434 Chemical denotes NADPH MESH:D009249
793 3446-3460 Chemical denotes methylene blue MESH:D008751
794 3469-3479 Chemical denotes -methylene MESH:C030011
795 2408-2416 Disease denotes COVID-19 MESH:C000657245
796 2591-2606 Disease denotes G6PD deficiency MESH:D005955
797 2848-2863 Disease denotes G6PD deficiency MESH:D005955
798 3068-3083 Disease denotes G6PD deficiency MESH:D005955
799 3087-3102 Disease denotes G6PD deficiency MESH:D005955
800 3261-3278 Disease denotes methemoglobinemia MESH:D008708
801 3333-3348 Disease denotes G6PD deficiency MESH:D005955
825 3555-3560 Gene denotes MetHb Gene:3048
826 4468-4473 Gene denotes MetHb Gene:3048
827 3972-3980 Species denotes patients Tax:9606
828 4135-4143 Species denotes patients Tax:9606
829 4563-4571 Species denotes patients Tax:9606
830 3664-3676 Chemical denotes nitric oxide MESH:D009569
831 4526-4529 Chemical denotes tHb
832 3708-3714 Disease denotes anemia MESH:D000740
833 3721-3727 Disease denotes Anemia MESH:D000740
834 3754-3763 Disease denotes infection MESH:D007239
835 3813-3819 Disease denotes anemia MESH:D000740
836 3823-3835 Disease denotes inflammation MESH:D007249
837 3986-3994 Disease denotes COVID-19 MESH:C000657245
838 4007-4013 Disease denotes anemic MESH:D000740
839 4061-4067 Disease denotes anemia MESH:D000740
840 4071-4083 Disease denotes inflammation MESH:D007249
841 4149-4155 Disease denotes anemia MESH:D000740
842 4214-4223 Disease denotes mortality MESH:D003643
843 4276-4282 Disease denotes anemia MESH:D000740
844 4299-4305 Disease denotes Anemia MESH:D000740
845 4404-4411 Disease denotes hypoxia MESH:D000860
846 4495-4501 Disease denotes anemia MESH:D000740
847 4554-4562 Disease denotes COVID-19 MESH:C000657245
869 4897-4902 Gene denotes MetHb Gene:3048
870 4808-4813 Gene denotes MetHb Gene:3048
871 4763-4768 Gene denotes MetHb Gene:3048
872 4632-4637 Gene denotes MetHb Gene:3048
873 4659-4666 Species denotes patient Tax:9606
874 4914-4922 Species denotes patients Tax:9606
875 5388-5417 Species denotes Plasmodium yoelii nigeriensis Tax:31274
876 5429-5448 Species denotes Plasmodium knowlesi Tax:5850
877 4617-4620 Chemical denotes tHb
878 4650-4658 Disease denotes COVID-19 MESH:C000657245
879 4788-4794 Disease denotes anemia MESH:D000740
880 4829-4842 Disease denotes anemic stress MESH:D000079225
881 4961-4967 Disease denotes anemia MESH:D000740
882 4971-4983 Disease denotes inflammation MESH:D007249
883 5004-5021 Disease denotes methemoglobinemia MESH:D008708
884 5023-5044 Disease denotes iron-deficient anemia MESH:D018798
885 5092-5109 Disease denotes methemoglobinemia MESH:D008708
886 5179-5196 Disease denotes methemoglobinemia MESH:D008708
887 5206-5221 Disease denotes viral infection MESH:D001102
888 5261-5270 Disease denotes infection MESH:D007239
889 5372-5382 Disease denotes infections MESH:D007239
897 5976-5981 Gene denotes MetHb Gene:3048
898 5528-5536 Species denotes patients Tax:9606
899 5623-5631 Species denotes patients Tax:9606
900 5893-5899 Species denotes humans Tax:9606
901 5489-5506 Disease denotes methemoglobinemia MESH:D008708
902 5519-5527 Disease denotes COVID-19 MESH:C000657245
903 5780-5787 Disease denotes fitness MESH:D012640
918 6061-6066 Gene denotes NF-κB Gene:4790
919 6123-6127 Gene denotes IL-8 Gene:3576
920 6143-6147 Gene denotes IL-6 Gene:3569
921 6188-6193 Gene denotes NF-κB Gene:4790
922 6254-6258 Gene denotes IL-8 Gene:3576
923 6277-6311 Gene denotes monocyte chemoattractant protein-1 Gene:6347
924 6313-6318 Gene denotes MCP-1 Gene:6347
925 6760-6764 Gene denotes IL-8 Gene:3576
926 6769-6773 Gene denotes IL-6 Gene:3569
927 6424-6429 Gene denotes MetHb Gene:3048
928 6375-6380 Gene denotes MetHb Gene:3048
929 5988-5993 Gene denotes MetHb Gene:3048
930 6539-6547 Disease denotes COVID-19 MESH:C000657245
931 6692-6699 Disease denotes hypoxia MESH:D000860

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T35 26-43 Phenotype denotes Methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T36 115-132 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T37 501-518 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T38 630-647 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T39 1131-1148 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T40 1333-1350 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T41 1377-1393 Phenotype denotes hemolytic anemia http://purl.obolibrary.org/obo/HP_0001878
T42 1465-1489 Phenotype denotes chronic hemolytic anemia http://purl.obolibrary.org/obo/HP_0004870
T43 3261-3278 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T44 3708-3714 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T45 3721-3727 Phenotype denotes Anemia http://purl.obolibrary.org/obo/HP_0001903
T46 3813-3819 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T47 4061-4067 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T48 4149-4155 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T49 4276-4282 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T50 4299-4305 Phenotype denotes Anemia http://purl.obolibrary.org/obo/HP_0001903
T51 4404-4411 Phenotype denotes hypoxia http://purl.obolibrary.org/obo/HP_0012418
T52 4495-4501 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T53 4788-4794 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T54 4961-4967 Phenotype denotes anemia http://purl.obolibrary.org/obo/HP_0001903
T55 5004-5021 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T56 5023-5044 Phenotype denotes iron-deficient anemia http://purl.obolibrary.org/obo/HP_0001891
T57 5092-5109 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T58 5138-5154 Phenotype denotes oxidative stress http://purl.obolibrary.org/obo/HP_0025464
T59 5179-5196 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T60 5489-5506 Phenotype denotes methemoglobinemia http://purl.obolibrary.org/obo/HP_0012119
T61 5928-5944 Phenotype denotes oxidative stress http://purl.obolibrary.org/obo/HP_0025464
T62 6557-6571 Phenotype denotes cytokine storm http://purl.obolibrary.org/obo/HP_0033041
T63 6692-6699 Phenotype denotes hypoxia http://purl.obolibrary.org/obo/HP_0012418

LitCovid-sentences

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].