Abstract_AJ0 
COVID-19_NN1 ,_PUN caused_VVN by_PRP SARS-CoV-2_NP0 infection_NN1 ,_PUN has_VHZ led_VVN to_PRP a_AT0 pandemic_AJ0 of_PRF acute_AJ0 respiratory_AJ0 illness_NN1 ._SENT Pharmacologic_AJ0 treatments_NN2 for_PRP COVID-19_NN1 have_VHB included_VVN treatments_NN2 targeting_VVG infection_NN1 prevention_NN1 ,_PUN prevention_NN1 of_PRF viral_AJ0 replication_NN1 ,_PUN reducing_VVG inflammation_NN1 and_CJC managing_AJ0 symptoms_NN2 of_PRF respiratory_AJ0 failure_NN1 caused_VVN by_PRP the_AT0 disease_NN1 ._SENT This_DT0 is_VBZ a_AT0 review_NN1 of_PRF key_AJ0 pharmacologic_AJ0 treatments_NN2 for_PRP COVID-19_NN1 based_VVN on_PRP peer-reviewed_AJ0 articles_NN2 from_PRP 2020._CRD 
Key_AJ0 Words_NN2 :_PUN COVID-19_CRD ,_PUN SARS-CoV-2_NP0 ,_PUN Remdesivir_NP0 ,_PUN REGN-CoV-2_CRD ,_PUN Optate_NP0 ,_PUN Airway_NP0 pH_NN1 ,_PUN Dexamethasone_NN1 
Introduction_NN1 
The_AT0 novel_AJ0 coronavirus_NN1 ,_PUN severe_AJ0 acute_AJ0 respiratory_AJ0 syndrome_NN1 coronavirus_NN1 2_CRD (_PUL SARS-_NN1 CoV-2_CRD )_PUR ,_PUN was_VBD first_ORD identified_VVN in_PRP Wuhan_NP0 ,_PUN China_NP0 at_PRP the_AT0 end_NN1 of_PRF 2019._CRD Since_PRP that_DT0 time_NN1 ,_PUN it_PNP has_VHZ affected_VVN over_PRP 100_CRD million_CRD people_NN0 around_PRP the_AT0 world_NN1 leading_VVG to_PRP over_AV0 2_CRD million_CRD deaths_NN2 ._SENT The_AT0 virus_NN1 causes_VVZ an_AT0 acute_AJ0 respiratory_AJ0 illness_NN1 that_CJT the_AT0 World_NN1 Health_NN1 Organization_NN1 has_VHZ termed_VVN Coronavirus_NP0 Disease_NN1 2019_CRD (_PUL COVID-19_CRD )_PUR ._SENT Due_AJ0 to_PRP the_AT0 severity_NN1 and_CJC effects_NN2 of_PRF this_DT0 illness_NN1 ,_PUN great_AJ0 efforts_NN2 have_VHB been_VBN undertaken_VVN to_TO0 identify_VVI effective_AJ0 pharmacologic_AJ0 therapies_NN2 to_TO0 prevent_VVI infection_NN1 ,_PUN prevent_VVB viral_AJ0 replication_NN1 ,_PUN prevent_VVB damaging_AJ0 inflammation_NN1 or_CJC to_TO0 manage_VVI the_AT0 symptoms_NN2 of_PRF respiratory_AJ0 failure_NN1 caused_VVN by_PRP the_AT0 virus_NN1 ._SENT 
This_DT0 reviews_VVZ six_CRD pharmacologic_AJ0 treatments_NN2 potentially_AV0 useful_AJ0 for_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT Remdesivir_NP0 ,_PUN REGN-CoV-2_CRD ,_PUN and_CJC Optate_VVB directly_AV0 target_VVB viral_AJ0 infection_NN1 and_CJC replication_NN1 ._SENT Dexamethasone_NN1 is_VBZ a_AT0 corticosteroid_NN1 that_CJT reduces_VVZ inflammation_NN1 post-infection_NN1 ._SENT 
Finally_AV0 ,_PUN oxygen_NN1 and_CJC inhaled_VVD pulmonary_AJ0 vasodilators_NN2 are_VBB used_VVN to_TO0 treat_VVI and_CJC manage_VVI respiratory_AJ0 symptoms_NN2 in_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT 
The_AT0 purpose_NN1 of_PRF this_DT0 article_NN1 is_VBZ to_TO0 review_VVI the_AT0 literature_NN1 available_AJ0 in_PRP the_AT0 past_AJ0 year_NN1 regarding_PRP these_DT0 pharmacologic_AJ0 therapies_NN2 for_PRP COVID-19_NN1 ._SENT Recent_AJ0 pharmacologic_AJ0 treatment_NN1 strategies_NN2 for_PRP COVID-19_NN1 will_VM0 also_AV0 be_VBI summarized_VVN ._SENT 
Methods_NN2 
Pharmacologic_AJ0 agents_NN2 included_VVN in_PRP the_AT0 National_AJ0 Institute_NN1 of_PRF Health_NN1 (_PUL NIH_NP0 )_PUR COVID-19_AJ0 Treatment_NN1 Guidelines_NN2 with_PRP the_AT0 most_AV0 supporting_AJ0 evidence_NN1 at_PRP the_AT0 time_NN1 of_PRF this_DT0 publication_NN1 were_VBD included_VVN in_PRP this_DT0 review_NN1 ._SENT A_AT0 PubMed_AJ0 search_NN1 was_VBD conducted_VVN to_TO0 identify_VVI articles_NN2 published_VVN in_PRP 2020_CRD that_DT0 related_VVN to_PRP these_DT0 COVID-19_AJ0 pharmacologic_AJ0 treatments_NN2 ._SENT Searches_NN2 were_VBD conducted_VVN using_VVG the_AT0 key_AJ0 words_NN2 "_PUQ remdesivir_NN1 "_PUQ ,_PUN "_PUQ REGN-CoV-2_NN1 "_PUQ ,_PUN "_PUQ Optate_NN1 "_PUQ ,_PUN "_PUQ dexamethasone_NN1 "_PUQ ,_PUN "_PUQ oxygen_NN1 "_PUQ and_CJC "_PUQ inhaled_AJ0 pulmonary_AJ0 vasodilators_NN2 "_PUQ in_PRP conjunction_NN1 with_PRP "_PUQ COVID-19_NN1 "_PUQ ._SENT A_AT0 summary_NN1 for_PRP each_DT0 of_PRF the_AT0 reviewed_VVN pharmacologic_AJ0 agents_NN2 ,_PUN based_VVN upon_PRP the_AT0 findings_NN2 of_PRF this_DT0 literature_NN1 search_NN1 ,_PUN is_VBZ included_VVN below_AV0 ._SENT 
Discussion_NN1 
Remdesivir_NN1 
Remdesivir_NP0 is_VBZ an_AT0 intravenous_AJ0 prodrug_NN1 of_PRF an_AT0 adenosine_NN1 analog_NN1 which_DTQ incorporates_VVZ into_PRP viral_AJ0 RNA_NN1 and_CJC results_NN2 in_PRP premature_AJ0 termination_NN1 ._SENT It_PNP has_VHZ a_AT0 broad-spectrum_AJ0 antiviral_AJ0 activity_NN1 against_PRP several_DT0 viruses_NN2 such_DT0 as_PRP respiratory_AJ0 syncytial_AJ0 virus_NN1 ,_PUN Nipah_NP0 virus_NN1 ,_PUN Ebola_NP0 virus_NN1 ,_PUN Middle_AJ0 East_NN1 respiratory_AJ0 syndrome_NN1 ,_PUN and_CJC severe_AJ0 acute_AJ0 respiratory_AJ0 syndrome_NN1 coronavirus-1_NN1 (_PUL SARS-CoV-1_NP0 )_PUR ._SENT Remdesivir_NP0 was_VBD authorized_VVN for_PRP emergency_NN1 use_NN1 by_PRP the_AT0 FDA_NN1 in_PRP May_NP0 of_PRF 2020_CRD for_PRP hospitalized_AJ0 adults_NN2 with_PRP severe_AJ0 COVID-19_NN1 ._SENT This_DT0 emergency_NN1 use_NN1 authorization_NN1 led_VVN to_PRP a_AT0 double_AJ0 blind_NN1 ,_PUN randomized_AJ0 ,_PUN placebo-controlled_AJ0 trial_NN1 sponsored_VVN by_PRP the_AT0 National_AJ0 Institutes_NN2 of_PRF Health_NN1 ._SENT 
This_DT0 initial_AJ0 trial_NN1 enrolled_VVD hospitalized_AJ0 adults_NN2 with_PRP confirmed_AJ0 cases_NN2 of_PRF COVID-19_NN1 and_CJC evidence_NN1 of_PRF lower_AJC respiratory_AJ0 tract_NN1 infections_NN2 ,_PUN treated_VVD them_PNP with_PRP either_AV0 10_CRD days_NN2 of_PRF remdesivir_NN1 or_CJC placebo_NN1 ,_PUN and_CJC monitored_VVD their_DPS time_NN1 to_PRP recovery_NN1 ._SENT In_PRP this_DT0 study_NN1 ,_PUN subjects_NN2 who_PNQ received_VVD remdesivir_NP0 had_VHD a_AT0 significantly_AV0 decreased_AJ0 median_AJ0 recovery_NN1 time_NN1 compared_VVN to_PRP subjects_NN2 who_PNQ received_VVD the_AT0 placebo_NN1 (_PUL Figure_NN1 1_CRD ,_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 9-11_CRD vs_PRP 13-18_CRD )_PUR ._SENT Subjects_NN2 who_PNQ received_VVD remdesivir_NP0 were_VBD also_AV0 more_AV0 likely_AJ0 to_TO0 have_VHI clinical_AJ0 improvement_NN1 at_PRP day_NN1 15_CRD (_PUL odds_NN2 ratio_NN1 ,_PUN 1.5_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 1.2-1.9_CRD ,_PUN after_PRP adjustment_NN1 for_PRP disease_NN1 severity_NN1 )_PUR when_CJS compared_VVN to_PRP those_DT0 treated_VVN with_PRP placebo_NN1 ._SENT Although_CJS there_EX0 was_VBD no_AT0 statistically_AV0 significant_AJ0 difference_NN1 in_PRP mortality_NN1 noted_VVN between_PRP the_AT0 two_CRD groups_NN2 ,_PUN the_AT0 authors_NN2 concluded_VVD that_CJT remdesivir_NP0 shortened_VVD the_AT0 time_NN1 to_PRP recovery_NN1 and_CJC hastened_VVD clinical_AJ0 improvement_NN1 when_CJS compared_VVN to_PRP the_AT0 placebo_NN1 group_NN1 and_CJC may_VM0 have_VHI prevented_VVN progression_NN1 to_PRP more_DT0 serious_AJ0 illness_NN1 in_PRP some_DT0 cases_NN2 ._SENT 
A_AT0 subsequent_AJ0 trial_NN1 evaluated_VVD different_AJ0 courses_NN2 of_PRF remdesivir_NP0 (_PUL 5_CRD days_NN2 vs_PRP 10_CRD days_NN2 )_PUR compared_VVN each_DT0 other_NN1 and_CJC the_AT0 standard_NN1 of_PRF care_NN1 ._SENT Subjects_NN2 who_PNQ received_VVD 5_CRD days_NN2 of_PRF remdesivir_NN1 had_VHD significantly_AV0 higher_AJC odds_NN2 of_PRF having_VHG a_AT0 better_AJC clinical_AJ0 status_NN1 than_CJS those_DT0 receiving_AJ0 standard_AJ0 care_NN1 alone_AV0 (_PUL odds_NN2 ratio_NN1 ,_PUN 1.65_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 1.09-2.48_CRD ;_PUN P_ZZ0 =_NN1 0.02_CRD )_PUR ._SENT Of_PRF note_NN1 ,_PUN those_DT0 who_PNQ received_VVD 10_CRD days_NN2 of_PRF remdesivir_NN1 therapy_NN1 did_VDD not_XX0 show_VVI a_AT0 statistically_AV0 significant_AJ0 difference_NN1 when_CJS compared_VVN to_PRP the_AT0 standard_NN1 of_PRF care_NN1 group_NN1 (_PUL P_ZZ0 =_NN1 0.18_CRD )_PUR and_CJC there_EX0 was_VBD no_AT0 significant_AJ0 difference_NN1 in_PRP mortality_NN1 between_PRP the_AT0 three_CRD groups_NN2 after_PRP 28_CRD days_NN2 ._SENT Although_CJS repeated_AJ0 studies_NN2 suggest_VVB that_CJT remdesivir_NN1 is_VBZ a_AT0 promising_AJ0 therapy_NN1 for_PRP COVID-19_AJ0 ,_PUN ongoing_AJ0 studies_NN2 are_VBB needed_VVN to_TO0 determine_VVI whether_CJS it_PNP reduces_VVZ mortality_NN1 ._SENT 
REGN-CoV-2_CRD 
REGN-CoV-2_NN1 is_VBZ an_AT0 antibody_NN1 cocktail_NN1 that_CJT prevents_VVZ viral_AJ0 entry_NN1 into_PRP human_AJ0 cells_NN2 via_PRP the_AT0 angiotensin_NN1 converting_VVG enzyme_NN1 2_CRD receptor_NN1 ._SENT It_PNP is_VBZ made_VVN up_AVP of_PRF two_CRD noncompeting_AJ0 ,_PUN neutralizing_AJ0 human_AJ0 IgG1_NN1 antibodies_NN2 ,_PUN REGN10933_CRD and_CJC REGN10987_CRD ,_PUN that_DT0 target_NN1 the_AT0 SARS-CoV-2_NP0 spike_NN1 protein_NN1 ._SENT Viruses_NN2 mutate_VVB frequently_AV0 which_DTQ may_VM0 result_VVI in_PRP new_AJ0 mutant_NN1 viruses_NN2 that_CJT are_VBB not_XX0 affected_VVN by_PRP a_AT0 specific_AJ0 antibody_NN1 –_PUN a_AT0 process_NN1 known_VVN as_PRP "_PUQ viral_AJ0 escape_NN1 "_PUQ ._SENT By_PRP combining_VVG two_CRD (_PUL or_CJC more_AV0 )_PUR antibodies_NN2 ,_PUN a_AT0 therapy_NN1 is_VBZ less_AV0 vulnerable_AJ0 to_PRP viral_AJ0 escape_NN1 because_CJS the_AT0 virus_NN1 would_VM0 have_VHI to_TO0 mutate_VVI in_PRP multiple_AJ0 specific_AJ0 ways_NN2 ._SENT 
Initial_AJ0 trials_NN2 evaluated_VVD the_AT0 effects_NN2 of_PRF 8.0_CRD g_NN0 or_CJC 2.4_CRD g_NN0 of_PRF REGN-CoV-2_NN1 compared_VVN to_PRP placebo_NN1 on_PRP non-hospitalized_AJ0 subjects_NN2 with_PRP COVID-19_NN1 ._SENT Subjects_NN2 that_CJT received_VVD either_DT0 dose_NN1 of_PRF REGN-CoV-2_NN1 had_VHD a_AT0 significantly_AV0 decreased_AJ0 SARS-CoV-2_AJ0 viral_AJ0 load_NN1 than_CJS those_DT0 that_CJT received_VVD the_AT0 placebo_NN1 (_PUL Figure_NN1 2_CRD ,_PUN 95_CRD %_NN0 CI_NP0 ,_PUN −1.02_CRD to_PRP −0.11_CRD )_PUR ._SENT Additionally_AV0 ,_PUN medical_AJ0 visits_NN2 for_PRP COVID-19_NN1 were_VBD significantly_AV0 decreased_VVN in_PRP subjects_NN2 that_CJT received_VVD REGN-CoV-2_AJ0 than_CJS those_DT0 that_CJT received_VVD the_AT0 placebo_NN1 (_PUL 95_CRD %_NN0 CI_NP0 ,_PUN −29_CRD to_PRP 11_CRD )_PUR 11._CRD As_CJS with_PRP remdesivir_NN1 ,_PUN further_AJC studies_NN2 are_VBB needed_VVN to_TO0 determine_VVI the_AT0 effects_NN2 of_PRF REGN-CoV-2_NN1 on_PRP mortality_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT 
Optate_NN1 
Optate_NN1 is_VBZ an_AT0 inhaled_AJ0 isotonic_AJ0 ,_PUN isosmotic_AJ0 ,_PUN alkaline_AJ0 medication_NN1 designed_VVN to_TO0 safely_AV0 raise_VVI airway_NN1 pH_NN1 without_PRP irritating_VVG the_AT0 airway_NN1 epithelium_NN1 ._SENT Raising_VVG intracellular_AJ0 pH_NN1 partially_AV0 prevents_VVZ activation_NN1 of_PRF SARS-CoV-2_NN1 in_PRP normal_AJ0 primary_AJ0 human_AJ0 airway_NN1 epithelial_AJ0 (_PUL NHAE_NP0 )_PUR cells_NN2 ,_PUN decreasing_VVG viral_AJ0 replication_NN1 by_PRP altering_VVG endosomal_AJ0 trafficking_NN1 and_CJC preventing_VVG viral_AJ0 entry_NN1 and_CJC replication12_NN1 ._SENT Optate_NN1 has_VHZ been_VBN previously_AV0 shown_VVN to_TO0 be_VBI safe_AJ0 to_TO0 inhale_VVI in_PRP healthy_AJ0 human_AJ0 subjects_NN2 and_CJC those_DT0 with_PRP stable_AJ0 airways_NN2 disease13_AJ0 ._SENT These_DT0 studies_NN2 also_AV0 demonstrated_VVN that_CJT Optate_AJ0 raised_AJ0 airway_NN1 lining_NN1 fluid_NN1 pH_NN1 ,_PUN with_PRP is_VBZ airway_NN1 epithelial_AJ0 extracellular_AJ0 pH._NN1 
In_PRP 2020_CRD ,_PUN in_PRP vitro_NN1 studies_NN2 demonstrated_VVD that_DT0 Optate_NN1 also_AV0 safely_AV0 increases_VVZ intracellular_AJ0 pH_NN1 of_PRF NHAE_NP0 cells_NN2 ._SENT Optate_NN1 also_AV0 ablated_VVN SARS-CoV-2_NP0 viral_AJ0 infection_NN1 and_CJC replication_NN1 in_PRP NHAE_NP0 cells_NN2 after_PRP 48_CRD hours_NN2 compared_VVN to_PRP placebo_NN1 (_PUL Figure_NN1 3_CRD ,_PUN P_ZZ0 <_NN1 0.001_CRD )_PUR ._SENT Due_AJ0 to_PRP its_DPS demonstrated_AJ0 safety_NN1 profile_NN1 in_PRP man_NN1 and_CJC anti-viral_AJ0 effects_NN2 in_PRP vitro_NN1 ,_PUN Optate_AJ0 inhalation_NN1 may_VM0 be_VBI well_AV0 suited_VVN for_PRP a_AT0 clinical_AJ0 trial_NN1 in_PRP patients_NN2 with_PRP COVID-19_AJ0 infection_NN1 ._SENT 
Dexamethasone_VVB 
Dexamethasone_NN1 is_VBZ a_AT0 potent_AJ0 corticosteroid_NN1 with_PRP anti-inflammatory_AJ0 properties_NN2 that_CJT has_VHZ often_AV0 been_VBN used_VVN as_PRP a_AT0 supplemental_AJ0 treatment_NN1 for_PRP viral_AJ0 pneumonia15_NN1 ._SENT Inflammation_NN1 is_VBZ a_AT0 known_AJ0 component_NN1 of_PRF COVID-19_NN1 ,_PUN leading_VVG to_PRP rationale_NN1 of_PRF dexamethasone_NN1 as_PRP a_AT0 potential_AJ0 therapy_NN1 ._SENT The_AT0 RECOVERY_NN1 Trial_NN1 Collaborative_AJ0 Group_NN1 performed_VVD a_AT0 randomized_AJ0 ,_PUN controlled_AJ0 ,_PUN open_AJ0 label_NN1 trial_NN1 comparing_VVG subjects_NN2 treated_VVN with_PRP oral_AJ0 or_CJC intravenous_AJ0 dexamethasone_NN1 (_PUL 6_CRD mg_NN0 daily_AJ0 for_PRP up_AVP to_PRP 10_CRD days_NN2 )_PUR to_PRP those_DT0 who_PNQ received_VVD the_AT0 standard_NN1 of_PRF care_NN1 alone_AJ0 and_CJC assessed_AJ0 mortality_NN1 at_PRP 28_CRD days_NN2 ._SENT They_PNP found_VVD that_CJT those_DT0 who_PNQ received_VVD dexamethasone_NN1 had_VHD significantly_AV0 decreased_VVN mortality_NN1 within_PRP 28_CRD days_NN2 compared_VVN to_PRP those_DT0 who_PNQ received_VVD the_AT0 standard_NN1 of_PRF care_NN1 (_PUL Figure_NN1 4_CRD ,_PUN 22.9_CRD %_NN0 vs_PRP 25.7_CRD %_NN0 ,_PUN age-adjusted_AJ0 rate_NN1 ratio_NN1 ,_PUN 0.83_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 0.75_CRD to_PRP 0.93_CRD ;_PUN P_ZZ0 <_NN1 0.001_CRD )_PUR ._SENT Subjects_NN2 requiring_VVG mechanical_AJ0 ventilation_NN1 at_PRP the_AT0 time_NN1 of_PRF randomization_NN1 also_AV0 had_VHD lower_AJC mortality_NN1 rates_NN2 when_CJS receiving_VVG dexamethasone_NN1 therapy_NN1 compared_VVN to_PRP the_AT0 standard_NN1 of_PRF care_NN1 (_PUL Figure_NN1 4_CRD ,_PUN 29.3_CRD %_NN0 vs._PRP 41.4_CRD %_NN0 ;_PUN rate_NN1 ratio_NN1 ,_PUN 0.64_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 0.51_CRD to_PRP 0.81_CRD )_PUR ._SENT Similarly_AV0 ,_PUN those_DT0 receiving_VVG non-invasive_AJ0 oxygen_NN1 therapy_NN1 at_PRP the_AT0 time_NN1 of_PRF randomization_NN1 had_VHD lower_AJC mortality_NN1 rates_NN2 when_CJS they_PNP were_VBD randomized_VVN to_PRP the_AT0 dexamethasone_NN1 group_NN1 (_PUL Figure_NN1 4_CRD ,_PUN 23.3_CRD %_NN0 vs._PRP 26.2_CRD %_NN0 ;_PUN rate_NN1 ratio_NN1 ,_PUN 0.82_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 0.72_CRD to_PRP 0.94_CRD )_PUR ._SENT Of_PRF note_NN1 ,_PUN this_DT0 decrease_NN1 in_PRP mortality_NN1 was_VBD not_XX0 noted_VVN in_PRP subjects_NN2 who_PNQ did_VDD not_XX0 require_VVI oxygen_NN1 therapy_NN1 at_PRP time_NN1 of_PRF randomization_NN1 (_PUL Figure_NN1 4_CRD ,_PUN 17.8_CRD %_NN0 vs._PRP 14.0_CRD %_NN0 ;_PUN rate_NN1 ratio_NN1 ,_PUN 1.19_CRD ;_PUN 95_CRD %_NN0 CI_NP0 ,_PUN 0.92_CRD to_PRP 1.55_CRD )_PUR ._SENT 
Oxygen_NN1 
Hypoxic_AJ0 respiratory_AJ0 failure_NN1 is_VBZ a_AT0 severe_AJ0 complication_NN1 of_PRF SARS-CoV-2_NN1 and_CJC affects_VVZ approximately_AV0 19_CRD %_NN0 of_PRF patients_NN2 with_PRP COVID-1918_NP0 ._SENT The_AT0 Surviving_AJ0 Sepsis_NP0 Campaign_NN1 COVID-19_NN1 panel_NN1 issued_VVD several_DT0 recommendations_NN2 regarding_PRP oxygen_NN1 use_NN1 in_PRP adults_NN2 with_PRP COVID-19_NN1 ,_PUN including_PRP :_PUN 
•_PUN Start_VVB supplemental_AJ0 oxygen_NN1 if_CJS the_AT0 peripheral_AJ0 oxygen_NN1 saturation_NN1 (_PUL SpO2_NP0 )_PUR is_VBZ <_NN1 92_CRD %_NN0 (_PUL weak_AJ0 recommendation_NN1 )_PUR ;_PUN 
•_PUN Start_VVB supplemental_AJ0 oxygen_NN1 if_CJS SpO2_NP0 is_VBZ <_NN1 90_CRD %_NN0 (_PUL strong_AJ0 recommendation_NN1 )_PUR ;_PUN 
•_PUN Maintain_VVB SpO2_NP0 no_AT0 higher_AJC than_CJS 96_CRD %_NN0 in_PRP patients_NN2 with_PRP acute_AJ0 hypoxemic_AJ0 respiratory_AJ0 failure_NN1 requiring_VVG oxygen_NN1 (_PUL strong_AJ0 recommendation_NN1 )_PUR ._SENT 
There_EX0 is_VBZ some_DT0 rationale_NN1 for_PRP heightened_AJ0 caution_NN1 of_PRF the_AT0 overuse_NN1 of_PRF supplemental_AJ0 oxygen_NN1 therapy_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 due_AJ0 to_TO0 concern_VVI for_PRP upregulation_NN1 of_PRF SARS-CoV-2_NP0 receptor_NN1 expression_NN1 in_PRP airway_NN1 epithelium_NN1 ._SENT Increased_AJ0 receptor_NN1 expression_NN1 could_VM0 lead_VVI to_PRP increased_AJ0 susceptibility_NN1 to_PRP SARS-CoV-2_NP0 infection_NN1 ._SENT Myti_NP0 et_NP0 al_NP0 compared_VVD levels_NN2 of_PRF mRNA_NN1 for_PRP genes_NN2 encoding_VVG SARS-CoV-2_AJ0 receptors_NN2 in_PRP lung_NN1 cells_NN2 of_PRF mouse_NN1 pups_NN2 and_CJC preterm_VVB human_AJ0 infants_NN2 exposed_VVN to_PRP chronically_AV0 elevated_AJ0 FiO2_NN1 (_PUL >_NN1 0.5_CRD )_PUR 20._CRD Levels_NN2 of_PRF two_CRD different_AJ0 SARS-CoV-2_AJ0 receptors_NN2 ,_PUN TMPRSS2_NP0 and_CJC TMPRSS11D_NP0 ,_PUN were_VBD both_AV0 increased_VVN in_PRP the_AT0 groups_NN2 treated_VVN with_PRP high_AJ0 FiO2_NN1 (_PUL Figure_NN1 5_CRD ,_PUN P_ZZ0 <_NN1 0.001_CRD )_PUR ._SENT Increased_AJ0 levels_NN2 of_PRF SARS-CoV-2_AJ0 receptors_NN2 could_VM0 increase_VVI susceptibility_NN1 to_PRP infection_NN1 ,_PUN however_AV0 ,_PUN further_AJC studies_NN2 determining_VVG the_AT0 effects_NN2 of_PRF oxygen_NN1 on_PRP SARS-CoV-2_NP0 infection_NN1 in_PRP vivo_NN1 are_VBB warranted_VVN ._SENT 
Inhaled_VVD Pulmonary_AJ0 Vasodilators_NN2 
Inhaled_VVD pulmonary_AJ0 vasodilators_NN2 have_VHB been_VBN shown_VVN to_TO0 improve_VVI oxygenation_NN1 and_CJC VQ_NP0 mismatch_NN1 in_PRP patients_NN2 with_PRP ARDS_NP0 ,_PUN which_DTQ could_VM0 lead_VVI to_PRP benefits_NN2 in_PRP patients_NN2 suffering_VVG from_PRP COVID-19_NN1 ._SENT Inhaled_AJ0 pulmonary_AJ0 vasodilators_NN2 include_VVB inhaled_AJ0 nitric_AJ0 oxide_NN1 ,_PUN prostacyclins_NN2 and_CJC prostacyclin_NN1 analogs_NN2 ._SENT At_PRP the_AT0 time_NN1 of_PRF this_DT0 publication_NN1 ,_PUN the_AT0 Surviving_AJ0 Sepsis_NP0 Campaign_NN1 for_PRP COVID-19_AJ0 panel_NN1 does_VDZ not_XX0 recommends_VVZ the_AT0 routine_AJ0 use_NN1 of_PRF inhaled_AJ0 pulmonary_AJ0 vasodilators_NN2 for_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT They_PNP do_VDB recommend_VVI a_AT0 trial_NN1 of_PRF inhaled_AJ0 pulmonary_AJ0 vasodilators_NN2 for_PRP mechanically_AV0 ventilated_AJ0 adults_NN2 with_PRP severe_AJ0 ARDS_NP0 and_CJC hypoxemia_NN1 secondary_AJ0 to_PRP COVID-19_AJ0 and_CJC refractory_AJ0 to_PRP optimized_AJ0 ventilation_NN1 and_CJC other_AJ0 rescue_NN1 strategies_NN2 ._SENT However_AV0 ,_PUN this_DT0 is_VBZ a_AT0 weak_AJ0 recommendation_NN1 with_PRP low_AJ0 quality_NN1 evidence_NN1 ._SENT 
Franco_NP0 et_NP0 al._NP0 explored_VVD the_AT0 mechanism_NN1 of_PRF action_NN1 of_PRF several_DT0 inhaled_AJ0 pulmonary_AJ0 vasodilators_NN2 and_CJC current_AJ0 ongoing_AJ0 clinical_AJ0 trials_NN2 ._SENT They_PNP discussed_VVD the_AT0 potential_AJ0 benefits_NN2 of_PRF nitric_AJ0 oxide_NN1 for_PRP benefit_NN1 patients_NN2 with_PRP COVID-19_NN1 by_PRP directly_AV0 treating_VVG endothelial_AJ0 dysfunction_NN1 /_PUN VQ_NP0 mismatch_NN1 ,_PUN improving_VVG cardiac_AJ0 reserve_NN1 ,_PUN and_CJC by_PRP direct_AJ0 anti-viral_AJ0 effects_NN2 ._SENT Currently_AV0 ,_PUN a_AT0 clinical_AJ0 trial_NN1 is_VBZ underway_AV0 to_TO0 assess_VVI these_DT0 benefits_NN2 as_CJS well_AV0 as_CJS the_AT0 safety_NN1 of_PRF pulsed_AJ0 inhaled_AJ0 nitric_AJ0 oxide_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 requiring_VVG supplemental_AJ0 oxygen_NN1 ._SENT Studies_NN2 are_VBB also_AV0 ongoing_AJ0 evaluating_VVG that_DT0 effects_NN2 of_PRF inhaled_AJ0 prostacyclin_NN1 therapy_NN1 on_PRP outcomes_NN2 for_PRP mechanically_AV0 ventilated_AJ0 adults_NN2 with_PRP COVID-19_NN1 ._SENT 
Summary_NN1 
In_PRP 2020_CRD ,_PUN several_DT0 pharmacologic_AJ0 agents_NN2 have_VHB been_VBN identified_VVN and_CJC trialed_VVN for_PRP use_NN1 in_PRP patients_NN2 suffering_VVG from_PRP COVID-19_NN1 ._SENT Several_DT0 of_PRF these_DT0 treatments_NN2 target_VVB viral_AJ0 replication_NN1 ,_PUN inflammation_NN1 ,_PUN and_CJC symptom_NN1 management_NN1 ._SENT Due_AJ0 to_PRP the_AT0 ongoing_AJ0 nature_NN1 of_PRF this_DT0 novel_NN1 pandemic_AJ0 ,_PUN recommendations_NN2 for_PRP treatment_NN1 of_PRF patients_NN2 with_PRP COVID-19_NN1 are_VBB ever_AV0 evolving_AJ0 ._SENT The_AT0 most_AV0 up-to-date_AJ0 guidelines_NN2 from_PRP the_AT0 NIH_NN1 can_VM0 be_VBI found_VVN at_PRP replaced-url_AJ0 Knowledge_NN1 of_PRF therapeutic_AJ0 options_NN2 and_CJC best_AJS practice_NN1 of_PRF their_DPS use_NN1 is_VBZ crucial_AJ0 for_PRP battling_VVG this_DT0 pandemic_AJ0 ._SENT Of_PRF note_NN1 ,_PUN at_PRP the_AT0 time_NN1 of_PRF this_DT0 publication_NN1 ,_PUN vaccination_NN1 against_PRP SARS-CoV-2_NP0 is_VBZ recommended_VVN as_PRP an_AT0 effective_AJ0 prevention_NN1 of_PRF COVID-19_NN1 ._SENT 
Figure_NN1 Legends_NN2 
Figure_NN1 1_CRD :_PUN Remdesivir_NP0 shortens_VVZ time_NN1 to_PRP recovery_NN1 in_PRP patients_NN2 with_PRP COVID-19_NN1 ._SENT Subjects_NN2 who_PNQ received_VVD remdesivir_NP0 had_VHD a_AT0 median_AJ0 recovery_NN1 time_NN1 of_PRF 10_CRD d_ZZ0 (_PUL 95_CRD %_NN0 CI_NP0 9_CRD –_PUN 11_CRD d_ZZ0 )_PUR compared_VVN to_PRP subjects_NN2 who_PNQ received_VVD the_AT0 placebo_NN1 whose_DTQ median_AJ0 recovery_NN1 time_NN1 was_VBD 15_CRD d_ZZ0 (_PUL 95_CRD %_NN0 CI_NP0 13_CRD –_PUN 18_CRD d_ZZ0 )_PUR ._SENT Data_NN0 from_PRP Reference_NN1 7._CRD 
Figure_NN1 2_CRD :_PUN REGN-CoV-2_CRD significantly_AV0 decreases_VVZ viral_AJ0 load_NN1 compared_VVN to_PRP placebo_NN1 ._SENT Time-weighted_AJ0 average_AJ0 change_NN1 in_PRP viral_AJ0 load_NN1 from_PRP day_NN1 1_CRD to_PRP day_NN1 7._CRD Subjects_NN2 that_CJT received_VVD REGN-CoV-2_NP0 SARS-CoV-2_NP0 had_VHD a_AT0 significantly_AV0 decreased_AJ0 SARS-CoV-2_AJ0 viral_AJ0 load_NN1 than_CJS those_DT0 that_CJT received_VVD the_AT0 placebo_NN1 (_PUL 95_CRD %_NN0 CI_NP0 −1.02_CRD to_PRP −0.11_CRD )_PUR ._SENT Data_NN0 from_PRP Reference_NN1 11._CRD 
Figure_NN1 3_CRD :_PUN Optate_NN1 decreases_VVZ SARS-CoV-2_AJ0 viral_AJ0 replication_NN1 in_PRP Vero_NP0 E6_CRD and_CJC NHAE_NP0 cells_NN2 ._SENT A_ZZ0 :_PUN PFUs_NP0 were_VBD measured_VVN in_PRP culture_NN1 media_NN0 from_PRP control_NN1 and_CJC Optate-treated_AJ0 Vero_NN1 E6_NN1 cells_NN2 infected_VVN with_PRP SARS-CoV-2_NP0 ._SENT Optate_AJ0 ablated_AJ0 viral_AJ0 infection_NN1 in_PRP the_AT0 Vero_NN1 E6_NN1 cells_NN2 (_PUL P_ZZ0 <_NN1 .001_CRD )_PUR ._SENT B_ZZ0 :_PUN Control_NN1 and_CJC Optate-treated_AJ0 primary_AJ0 NHAE_NP0 cell_NN1 cultures_NN2 were_VBD infected_VVN with_PRP SARS-CoV-2_NP0 ,_PUN PFUs_NN1 in_PRP culture_NN1 media_NN0 were_VBD analyzed_VVN under_PRP similar_AJ0 conditions_NN2 for_PRP 120_CRD h_ZZ0 ,_PUN starting_VVG from_PRP 24_CRD h_ZZ0 after_PRP infection_NN1 ._SENT After_CJS infection_NN1 was_VBD established_VVN (_PUL 24_CRD h_ZZ0 )_PUR ,_PUN viral_AJ0 infection_NN1 was_VBD ablated_VVN in_PRP the_AT0 Optate-treated_AJ0 cells_NN2 (_PUL P_ZZ0 <_NN1 .001_CRD )_PUR ._SENT From_PRP Reference_NN1 14._CRD 
Figure_NN1 4_CRD :_PUN Dexamethasone_NN1 decreases_VVZ mortality_NN1 in_PRP hospitalized_AJ0 patients_NN2 with_PRP COVID-19_NN1 ._SENT Shown_VVN is_VBZ the_AT0 effect_NN1 of_PRF dexamethasone_NN1 on_PRP 28-d_AJ0 mortality_NN1 according_VVG to_PRP respiratory_AJ0 support_NN1 at_PRP time_NN1 of_PRF randomization_NN1 ._SENT Subgroups_NN2 include_VVB all_DT0 subjects_NN2 ,_PUN those_DT0 undergoing_VVG mechanical_AJ0 ventilation_NN1 ,_PUN those_DT0 receiving_VVG supplemental_AJ0 oxygen_NN1 ,_PUN and_CJC those_DT0 who_PNQ were_VBD receiving_VVG no_AT0 oxygen_NN1 at_PRP the_AT0 time_NN1 of_PRF randomization_NN1 ._SENT Data_NN0 from_PRP Reference_NN1 17._CRD 
Figure_NN1 5_CRD :_PUN Steady-state_AJ0 levels_NN2 of_PRF lung_NN1 mRNA_NN1 transcripts_NN2 encoding_VVG SARS-CoV-2_AJ0 entry_NN1 receptors_NN2 and_CJC co-receptors_NN2 in_PRP experimental_AJ0 animals_NN2 and_CJC clinical_AJ0 subjects_NN2 chronically_AV0 exposed_VVN to_PRP elevated_AJ0 FiO2_NN1 ._SENT A_ZZ0 :_PUN mRNA_NN1 levels_NN2 of_PRF Ace2_CRD ,_PUN Tmprss1_CRD ,_PUN Tmprss2_CRD ,_PUN and_CJC Tmprss11d_NP0 in_PRP mouse_NN1 pup_NN1 lungs_NN2 (_PUL 5_CRD animals_NN2 per_PRP group_NN1 )_PUR at_PRP post-natal_AJ0 day_NN1 (_PUL P_ZZ0 )_PUR 2_CRD ,_PUN 3_CRD ,_PUN 5_CRD ,_PUN 10_CRD ,_PUN and_CJC 14_CRD ,_PUN and_CJC then_AV0 exposed_VVN to_PRP room_NN1 air_NN1 (_PUL FiO2_NP0 0.21_CRD ;_PUN white_AJ0 bars_NN2 )_PUR or_CJC hyperoxia_NN1 (_PUL FiO2_NP0 0.85_CRD ;_PUN black_AJ0 bars_NN2 )_PUR for_PRP the_AT0 first_ORD 14_CRD d_ZZ0 of_PRF post-natal_AJ0 life_NN1 ._SENT 
