PMC:7558914 / 8438-14868 JSONTXT

{"project":"LitCovid_Glycan-Motif-Structure","denotations":[{"id":"T5","span":{"begin":5156,"end":5163},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T6","span":{"begin":5156,"end":5163},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T7","span":{"begin":5203,"end":5210},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T8","span":{"begin":5203,"end":5210},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T9","span":{"begin":5259,"end":5266},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T10","span":{"begin":5259,"end":5266},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T11","span":{"begin":5380,"end":5387},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T12","span":{"begin":5380,"end":5387},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T13","span":{"begin":5620,"end":5627},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T14","span":{"begin":5620,"end":5627},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T15","span":{"begin":5786,"end":5793},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T16","span":{"begin":5786,"end":5793},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T17","span":{"begin":5870,"end":5877},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T18","span":{"begin":5870,"end":5877},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T19","span":{"begin":6033,"end":6040},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T20","span":{"begin":6033,"end":6040},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"}],"text":"3. Results\nSymptomatic treatment, recommendations for infection prevention and control, and recommendations for early identification of COVID-19 alarm symptoms were adopted for patients with mild upper respiratory illness without clinical risk factors and confirmed cases without symptoms.\nAntiviral treatment was recommended for patients with mild upper respiratory illness with clinical risk factors and patients with mild, moderate, and severe pneumonia. Patients could be treated with monotherapy using hydroxychloroquine or lopinavir/ritonavir; dual therapy with hydroxychloroquine plus azithromycin or lopinavir/ritonavir; or triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir. Hydroxychloroquine could be used in four different regimens, and lopinavir/ritonavir could be used in two different regimens, with varied dosages and duration of treatment—either a short (5-day) regimen or long (10-day) regimen. Azithromycin was recommended at the same dosage and duration of treatment. Protocols included the combination of all four hydroxychloroquine regimens with azithromycin. Regimens 1 and 3 of hydroxychloroquine were combined in dual therapy with the two regimens of lopinavir/ritonavir, which in turn were combined with azithromycin in triple therapy. Chloroquine 500 mg twice per day was recommended as an alternative when hydroxychloroquine was not available. In patients with three antiviral agents, lopinavir/ritonavir could be replaced with once-daily remdesivir if the patient was enrolled in a clinical trial. The dosage and durations of antiviral treatments are shown in Table 1.\nFor treating mild respiratory illness in patients with clinical risk factors, up to six antiviral options were found. Monotherapy with regimen 1 of hydroxychloroquine was the most frequent antiviral treatment recommended (5/15 protocols, 33.3%), followed by hydroxychloroquine regimen 1 plus azithromycin (3/15, 20%). Dual antiviral treatment using hydroxychloroquine with azithromycin or lopinavir/ritonavir in combination was found in 40% of protocols. No treatment was recommended in two protocols. In regard to mild pneumonia, 14 protocols recommended dual therapy: seven recommended hydroxychloroquine plus azithromycin, and seven recommended hydroxychloroquine plus lopinavir/ritonavir. Only one protocol did not recommend any antiviral treatment. For moderate pneumonia, hydroxychloroquine regimen 1 in combination with lopinavir/ritonavir regimen 2 was the most recommended treatment (5/15, 33.3%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (7/15, 46.7%) and triple therapy with hydroxychloroquine regimen 3, and azithromycin and lopinavir/ritonavir regimen 2 (6/15, 40%) were the most recommended treatments for patients with severe pneumonia. Most protocols showed a preference for dual or triple antiviral therapy for patients with pneumonia. Further details about recommended antiviral treatment of COVID-19 are summarized in Table 2.\nAll protocols recommended initiating empirical antibacterial treatment when secondary bacterial infection was suspected, according to local antibacterial therapy guidelines. Empirical antibiotics were also indicated when pneumonia was diagnosed in seven protocols regardless of suspected bacterial infection. Amoxicillin plus clavulanic acid or ceftriaxone were the main antibiotics recommended for use.\nAll protocol considered the management of ARDS with signs of cytokine release syndrome, which included elevation of interleukin-6, fibrinogen, D-dimer, and C-reactive protein levels [9]. The therapies (corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy) were recommended once these syndromes were observed. The choice of which therapy to use was made by physicians according to their own clinical judgment. Corticosteroids were widely included in all protocols; indeed, only 2 out of 15 hospitals did not include any corticosteroid regimen. There was a total of five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone. Dexamethasone was recommended in eight protocols with two different regimens: 20 mg (5/8, 62.5%) or 40 mg (3/8, 37.5%) daily. Methylprednisolone was included in 13 protocols with 2 different regimens: 125–250 mg (8/13, 61.5%) or 1 mg/kg (5/13, 38.5%) daily. Only one protocol included prednisone with a single regimen of 40 mg daily. The duration of treatment varied from 3 to 10 days, depending on the patient’s clinical condition. Tocilizumab was recommended in all protocols with the same dosage (400 or 600 mg) according to body weight. Anakinra was included in seven protocols with six different regimens. Immunoglobulins were included as possible therapy in three protocols. In six protocols, other optional therapies were included, such as sarilumab, baricitinib, colchicine, ciclosporin A, sirolimus, tacrolimus, and vitamin D, according to clinical trials. Dosage and durations of corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy are shown in Table 3.\nAll protocols included anticoagulant treatment (low-molecular-weight heparin as the first option and unfractionated heparin as an alternative) and recommended prophylactic heparin during hospitalization. In 8 of the 15 COVID-19 protocols (53.3%), the dose of prophylactic low-molecular-weight heparin was increased if there was a high risk of thrombosis (severe COVID-19 with evidence of cytokine release syndrome, previous venous thromboembolism or acute ischemic artery disease, or D-dimer \u003e3000 ng/mL). In five protocols (33.3%), heparin was increased to therapeutic doses if the condition was critical or if there was a progressive increase in D-dimer levels. All protocols included therapeutic heparin if there was evidence of venous thromboembolism. At discharge, prophylactic heparin was recommended if D-dimer \u003e1500-3000 ng/dL for 7 days or during the time of the expected severe immobilization in seven protocols (46.6%). Adjustments of heparin doses were indicated in the respective protocols.\nSupportive care, hospital circuits, ward organization, and care planning were included in all protocols. Drug side effects (including follow-up electrocardiogram for QT prolongation), interactions, nonrecommended treatment, or recommendation for other drugs were included in 11 protocols (73,3%), and discharge recommendations in 12 (80%)."}

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Results\nSymptomatic treatment, recommendations for infection prevention and control, and recommendations for early identification of COVID-19 alarm symptoms were adopted for patients with mild upper respiratory illness without clinical risk factors and confirmed cases without symptoms.\nAntiviral treatment was recommended for patients with mild upper respiratory illness with clinical risk factors and patients with mild, moderate, and severe pneumonia. Patients could be treated with monotherapy using hydroxychloroquine or lopinavir/ritonavir; dual therapy with hydroxychloroquine plus azithromycin or lopinavir/ritonavir; or triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir. Hydroxychloroquine could be used in four different regimens, and lopinavir/ritonavir could be used in two different regimens, with varied dosages and duration of treatment—either a short (5-day) regimen or long (10-day) regimen. Azithromycin was recommended at the same dosage and duration of treatment. Protocols included the combination of all four hydroxychloroquine regimens with azithromycin. Regimens 1 and 3 of hydroxychloroquine were combined in dual therapy with the two regimens of lopinavir/ritonavir, which in turn were combined with azithromycin in triple therapy. Chloroquine 500 mg twice per day was recommended as an alternative when hydroxychloroquine was not available. In patients with three antiviral agents, lopinavir/ritonavir could be replaced with once-daily remdesivir if the patient was enrolled in a clinical trial. The dosage and durations of antiviral treatments are shown in Table 1.\nFor treating mild respiratory illness in patients with clinical risk factors, up to six antiviral options were found. Monotherapy with regimen 1 of hydroxychloroquine was the most frequent antiviral treatment recommended (5/15 protocols, 33.3%), followed by hydroxychloroquine regimen 1 plus azithromycin (3/15, 20%). Dual antiviral treatment using hydroxychloroquine with azithromycin or lopinavir/ritonavir in combination was found in 40% of protocols. No treatment was recommended in two protocols. In regard to mild pneumonia, 14 protocols recommended dual therapy: seven recommended hydroxychloroquine plus azithromycin, and seven recommended hydroxychloroquine plus lopinavir/ritonavir. Only one protocol did not recommend any antiviral treatment. For moderate pneumonia, hydroxychloroquine regimen 1 in combination with lopinavir/ritonavir regimen 2 was the most recommended treatment (5/15, 33.3%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (7/15, 46.7%) and triple therapy with hydroxychloroquine regimen 3, and azithromycin and lopinavir/ritonavir regimen 2 (6/15, 40%) were the most recommended treatments for patients with severe pneumonia. Most protocols showed a preference for dual or triple antiviral therapy for patients with pneumonia. Further details about recommended antiviral treatment of COVID-19 are summarized in Table 2.\nAll protocols recommended initiating empirical antibacterial treatment when secondary bacterial infection was suspected, according to local antibacterial therapy guidelines. Empirical antibiotics were also indicated when pneumonia was diagnosed in seven protocols regardless of suspected bacterial infection. Amoxicillin plus clavulanic acid or ceftriaxone were the main antibiotics recommended for use.\nAll protocol considered the management of ARDS with signs of cytokine release syndrome, which included elevation of interleukin-6, fibrinogen, D-dimer, and C-reactive protein levels [9]. The therapies (corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy) were recommended once these syndromes were observed. The choice of which therapy to use was made by physicians according to their own clinical judgment. Corticosteroids were widely included in all protocols; indeed, only 2 out of 15 hospitals did not include any corticosteroid regimen. There was a total of five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone. Dexamethasone was recommended in eight protocols with two different regimens: 20 mg (5/8, 62.5%) or 40 mg (3/8, 37.5%) daily. Methylprednisolone was included in 13 protocols with 2 different regimens: 125–250 mg (8/13, 61.5%) or 1 mg/kg (5/13, 38.5%) daily. Only one protocol included prednisone with a single regimen of 40 mg daily. The duration of treatment varied from 3 to 10 days, depending on the patient’s clinical condition. Tocilizumab was recommended in all protocols with the same dosage (400 or 600 mg) according to body weight. Anakinra was included in seven protocols with six different regimens. Immunoglobulins were included as possible therapy in three protocols. In six protocols, other optional therapies were included, such as sarilumab, baricitinib, colchicine, ciclosporin A, sirolimus, tacrolimus, and vitamin D, according to clinical trials. Dosage and durations of corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy are shown in Table 3.\nAll protocols included anticoagulant treatment (low-molecular-weight heparin as the first option and unfractionated heparin as an alternative) and recommended prophylactic heparin during hospitalization. In 8 of the 15 COVID-19 protocols (53.3%), the dose of prophylactic low-molecular-weight heparin was increased if there was a high risk of thrombosis (severe COVID-19 with evidence of cytokine release syndrome, previous venous thromboembolism or acute ischemic artery disease, or D-dimer \u003e3000 ng/mL). In five protocols (33.3%), heparin was increased to therapeutic doses if the condition was critical or if there was a progressive increase in D-dimer levels. All protocols included therapeutic heparin if there was evidence of venous thromboembolism. At discharge, prophylactic heparin was recommended if D-dimer \u003e1500-3000 ng/dL for 7 days or during the time of the expected severe immobilization in seven protocols (46.6%). Adjustments of heparin doses were indicated in the respective protocols.\nSupportive care, hospital circuits, ward organization, and care planning were included in all protocols. Drug side effects (including follow-up electrocardiogram for QT prolongation), interactions, nonrecommended treatment, or recommendation for other drugs were included in 11 protocols (73,3%), and discharge recommendations in 12 (80%)."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T14","span":{"begin":202,"end":221},"obj":"Phenotype"},{"id":"T15","span":{"begin":355,"end":374},"obj":"Phenotype"},{"id":"T16","span":{"begin":447,"end":456},"obj":"Phenotype"},{"id":"T17","span":{"begin":1643,"end":1662},"obj":"Phenotype"},{"id":"T18","span":{"begin":2145,"end":2154},"obj":"Phenotype"},{"id":"T19","span":{"begin":2392,"end":2401},"obj":"Phenotype"},{"id":"T20","span":{"begin":2794,"end":2803},"obj":"Phenotype"},{"id":"T21","span":{"begin":2895,"end":2904},"obj":"Phenotype"},{"id":"T22","span":{"begin":3220,"end":3229},"obj":"Phenotype"},{"id":"T23","span":{"begin":3464,"end":3489},"obj":"Phenotype"},{"id":"T24","span":{"begin":5475,"end":5500},"obj":"Phenotype"},{"id":"T25","span":{"begin":5518,"end":5533},"obj":"Phenotype"},{"id":"T26","span":{"begin":5826,"end":5841},"obj":"Phenotype"}],"attributes":[{"id":"A14","pred":"hp_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/HP_0002086"},{"id":"A15","pred":"hp_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/HP_0002086"},{"id":"A16","pred":"hp_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A17","pred":"hp_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/HP_0002086"},{"id":"A18","pred":"hp_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A19","pred":"hp_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A20","pred":"hp_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A21","pred":"hp_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A22","pred":"hp_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A23","pred":"hp_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/HP_0033041"},{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0033041"},{"id":"A25","pred":"hp_id","subj":"T25","obj":"http://purl.obolibrary.org/obo/HP_0001907"},{"id":"A26","pred":"hp_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/HP_0001907"}],"text":"3. Results\nSymptomatic treatment, recommendations for infection prevention and control, and recommendations for early identification of COVID-19 alarm symptoms were adopted for patients with mild upper respiratory illness without clinical risk factors and confirmed cases without symptoms.\nAntiviral treatment was recommended for patients with mild upper respiratory illness with clinical risk factors and patients with mild, moderate, and severe pneumonia. Patients could be treated with monotherapy using hydroxychloroquine or lopinavir/ritonavir; dual therapy with hydroxychloroquine plus azithromycin or lopinavir/ritonavir; or triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir. Hydroxychloroquine could be used in four different regimens, and lopinavir/ritonavir could be used in two different regimens, with varied dosages and duration of treatment—either a short (5-day) regimen or long (10-day) regimen. Azithromycin was recommended at the same dosage and duration of treatment. Protocols included the combination of all four hydroxychloroquine regimens with azithromycin. Regimens 1 and 3 of hydroxychloroquine were combined in dual therapy with the two regimens of lopinavir/ritonavir, which in turn were combined with azithromycin in triple therapy. Chloroquine 500 mg twice per day was recommended as an alternative when hydroxychloroquine was not available. In patients with three antiviral agents, lopinavir/ritonavir could be replaced with once-daily remdesivir if the patient was enrolled in a clinical trial. The dosage and durations of antiviral treatments are shown in Table 1.\nFor treating mild respiratory illness in patients with clinical risk factors, up to six antiviral options were found. Monotherapy with regimen 1 of hydroxychloroquine was the most frequent antiviral treatment recommended (5/15 protocols, 33.3%), followed by hydroxychloroquine regimen 1 plus azithromycin (3/15, 20%). Dual antiviral treatment using hydroxychloroquine with azithromycin or lopinavir/ritonavir in combination was found in 40% of protocols. No treatment was recommended in two protocols. In regard to mild pneumonia, 14 protocols recommended dual therapy: seven recommended hydroxychloroquine plus azithromycin, and seven recommended hydroxychloroquine plus lopinavir/ritonavir. Only one protocol did not recommend any antiviral treatment. For moderate pneumonia, hydroxychloroquine regimen 1 in combination with lopinavir/ritonavir regimen 2 was the most recommended treatment (5/15, 33.3%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (7/15, 46.7%) and triple therapy with hydroxychloroquine regimen 3, and azithromycin and lopinavir/ritonavir regimen 2 (6/15, 40%) were the most recommended treatments for patients with severe pneumonia. Most protocols showed a preference for dual or triple antiviral therapy for patients with pneumonia. Further details about recommended antiviral treatment of COVID-19 are summarized in Table 2.\nAll protocols recommended initiating empirical antibacterial treatment when secondary bacterial infection was suspected, according to local antibacterial therapy guidelines. Empirical antibiotics were also indicated when pneumonia was diagnosed in seven protocols regardless of suspected bacterial infection. Amoxicillin plus clavulanic acid or ceftriaxone were the main antibiotics recommended for use.\nAll protocol considered the management of ARDS with signs of cytokine release syndrome, which included elevation of interleukin-6, fibrinogen, D-dimer, and C-reactive protein levels [9]. The therapies (corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy) were recommended once these syndromes were observed. The choice of which therapy to use was made by physicians according to their own clinical judgment. Corticosteroids were widely included in all protocols; indeed, only 2 out of 15 hospitals did not include any corticosteroid regimen. There was a total of five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone. Dexamethasone was recommended in eight protocols with two different regimens: 20 mg (5/8, 62.5%) or 40 mg (3/8, 37.5%) daily. Methylprednisolone was included in 13 protocols with 2 different regimens: 125–250 mg (8/13, 61.5%) or 1 mg/kg (5/13, 38.5%) daily. Only one protocol included prednisone with a single regimen of 40 mg daily. The duration of treatment varied from 3 to 10 days, depending on the patient’s clinical condition. Tocilizumab was recommended in all protocols with the same dosage (400 or 600 mg) according to body weight. Anakinra was included in seven protocols with six different regimens. Immunoglobulins were included as possible therapy in three protocols. In six protocols, other optional therapies were included, such as sarilumab, baricitinib, colchicine, ciclosporin A, sirolimus, tacrolimus, and vitamin D, according to clinical trials. Dosage and durations of corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy are shown in Table 3.\nAll protocols included anticoagulant treatment (low-molecular-weight heparin as the first option and unfractionated heparin as an alternative) and recommended prophylactic heparin during hospitalization. In 8 of the 15 COVID-19 protocols (53.3%), the dose of prophylactic low-molecular-weight heparin was increased if there was a high risk of thrombosis (severe COVID-19 with evidence of cytokine release syndrome, previous venous thromboembolism or acute ischemic artery disease, or D-dimer \u003e3000 ng/mL). In five protocols (33.3%), heparin was increased to therapeutic doses if the condition was critical or if there was a progressive increase in D-dimer levels. All protocols included therapeutic heparin if there was evidence of venous thromboembolism. At discharge, prophylactic heparin was recommended if D-dimer \u003e1500-3000 ng/dL for 7 days or during the time of the expected severe immobilization in seven protocols (46.6%). Adjustments of heparin doses were indicated in the respective protocols.\nSupportive care, hospital circuits, ward organization, and care planning were included in all protocols. Drug side effects (including follow-up electrocardiogram for QT prolongation), interactions, nonrecommended treatment, or recommendation for other drugs were included in 11 protocols (73,3%), and discharge recommendations in 12 (80%)."}

{"project":"LitCovid-sentences","denotations":[{"id":"T52","span":{"begin":0,"end":2},"obj":"Sentence"},{"id":"T53","span":{"begin":3,"end":10},"obj":"Sentence"},{"id":"T54","span":{"begin":11,"end":289},"obj":"Sentence"},{"id":"T55","span":{"begin":290,"end":457},"obj":"Sentence"},{"id":"T56","span":{"begin":458,"end":710},"obj":"Sentence"},{"id":"T57","span":{"begin":711,"end":939},"obj":"Sentence"},{"id":"T58","span":{"begin":940,"end":1014},"obj":"Sentence"},{"id":"T59","span":{"begin":1015,"end":1108},"obj":"Sentence"},{"id":"T60","span":{"begin":1109,"end":1288},"obj":"Sentence"},{"id":"T61","span":{"begin":1289,"end":1398},"obj":"Sentence"},{"id":"T62","span":{"begin":1399,"end":1553},"obj":"Sentence"},{"id":"T63","span":{"begin":1554,"end":1624},"obj":"Sentence"},{"id":"T64","span":{"begin":1625,"end":1742},"obj":"Sentence"},{"id":"T65","span":{"begin":1743,"end":1942},"obj":"Sentence"},{"id":"T66","span":{"begin":1943,"end":2079},"obj":"Sentence"},{"id":"T67","span":{"begin":2080,"end":2126},"obj":"Sentence"},{"id":"T68","span":{"begin":2127,"end":2317},"obj":"Sentence"},{"id":"T69","span":{"begin":2318,"end":2378},"obj":"Sentence"},{"id":"T70","span":{"begin":2379,"end":2531},"obj":"Sentence"},{"id":"T71","span":{"begin":2532,"end":2804},"obj":"Sentence"},{"id":"T72","span":{"begin":2805,"end":2905},"obj":"Sentence"},{"id":"T73","span":{"begin":2906,"end":2998},"obj":"Sentence"},{"id":"T74","span":{"begin":2999,"end":3172},"obj":"Sentence"},{"id":"T75","span":{"begin":3173,"end":3307},"obj":"Sentence"},{"id":"T76","span":{"begin":3308,"end":3402},"obj":"Sentence"},{"id":"T77","span":{"begin":3403,"end":3589},"obj":"Sentence"},{"id":"T78","span":{"begin":3590,"end":3743},"obj":"Sentence"},{"id":"T79","span":{"begin":3744,"end":3843},"obj":"Sentence"},{"id":"T80","span":{"begin":3844,"end":3977},"obj":"Sentence"},{"id":"T81","span":{"begin":3978,"end":4089},"obj":"Sentence"},{"id":"T82","span":{"begin":4090,"end":4167},"obj":"Sentence"},{"id":"T83","span":{"begin":4168,"end":4215},"obj":"Sentence"},{"id":"T84","span":{"begin":4216,"end":4290},"obj":"Sentence"},{"id":"T85","span":{"begin":4291,"end":4347},"obj":"Sentence"},{"id":"T86","span":{"begin":4348,"end":4423},"obj":"Sentence"},{"id":"T87","span":{"begin":4424,"end":4522},"obj":"Sentence"},{"id":"T88","span":{"begin":4523,"end":4630},"obj":"Sentence"},{"id":"T89","span":{"begin":4631,"end":4700},"obj":"Sentence"},{"id":"T90","span":{"begin":4701,"end":4770},"obj":"Sentence"},{"id":"T91","span":{"begin":4771,"end":4955},"obj":"Sentence"},{"id":"T92","span":{"begin":4956,"end":5086},"obj":"Sentence"},{"id":"T93","span":{"begin":5087,"end":5290},"obj":"Sentence"},{"id":"T94","span":{"begin":5291,"end":5592},"obj":"Sentence"},{"id":"T95","span":{"begin":5593,"end":5750},"obj":"Sentence"},{"id":"T96","span":{"begin":5751,"end":5842},"obj":"Sentence"},{"id":"T97","span":{"begin":5843,"end":6017},"obj":"Sentence"},{"id":"T98","span":{"begin":6018,"end":6090},"obj":"Sentence"},{"id":"T99","span":{"begin":6091,"end":6195},"obj":"Sentence"},{"id":"T100","span":{"begin":6196,"end":6430},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"3. Results\nSymptomatic treatment, recommendations for infection prevention and control, and recommendations for early identification of COVID-19 alarm symptoms were adopted for patients with mild upper respiratory illness without clinical risk factors and confirmed cases without symptoms.\nAntiviral treatment was recommended for patients with mild upper respiratory illness with clinical risk factors and patients with mild, moderate, and severe pneumonia. Patients could be treated with monotherapy using hydroxychloroquine or lopinavir/ritonavir; dual therapy with hydroxychloroquine plus azithromycin or lopinavir/ritonavir; or triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir. Hydroxychloroquine could be used in four different regimens, and lopinavir/ritonavir could be used in two different regimens, with varied dosages and duration of treatment—either a short (5-day) regimen or long (10-day) regimen. Azithromycin was recommended at the same dosage and duration of treatment. Protocols included the combination of all four hydroxychloroquine regimens with azithromycin. Regimens 1 and 3 of hydroxychloroquine were combined in dual therapy with the two regimens of lopinavir/ritonavir, which in turn were combined with azithromycin in triple therapy. Chloroquine 500 mg twice per day was recommended as an alternative when hydroxychloroquine was not available. In patients with three antiviral agents, lopinavir/ritonavir could be replaced with once-daily remdesivir if the patient was enrolled in a clinical trial. The dosage and durations of antiviral treatments are shown in Table 1.\nFor treating mild respiratory illness in patients with clinical risk factors, up to six antiviral options were found. Monotherapy with regimen 1 of hydroxychloroquine was the most frequent antiviral treatment recommended (5/15 protocols, 33.3%), followed by hydroxychloroquine regimen 1 plus azithromycin (3/15, 20%). Dual antiviral treatment using hydroxychloroquine with azithromycin or lopinavir/ritonavir in combination was found in 40% of protocols. No treatment was recommended in two protocols. In regard to mild pneumonia, 14 protocols recommended dual therapy: seven recommended hydroxychloroquine plus azithromycin, and seven recommended hydroxychloroquine plus lopinavir/ritonavir. Only one protocol did not recommend any antiviral treatment. For moderate pneumonia, hydroxychloroquine regimen 1 in combination with lopinavir/ritonavir regimen 2 was the most recommended treatment (5/15, 33.3%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (7/15, 46.7%) and triple therapy with hydroxychloroquine regimen 3, and azithromycin and lopinavir/ritonavir regimen 2 (6/15, 40%) were the most recommended treatments for patients with severe pneumonia. Most protocols showed a preference for dual or triple antiviral therapy for patients with pneumonia. Further details about recommended antiviral treatment of COVID-19 are summarized in Table 2.\nAll protocols recommended initiating empirical antibacterial treatment when secondary bacterial infection was suspected, according to local antibacterial therapy guidelines. Empirical antibiotics were also indicated when pneumonia was diagnosed in seven protocols regardless of suspected bacterial infection. Amoxicillin plus clavulanic acid or ceftriaxone were the main antibiotics recommended for use.\nAll protocol considered the management of ARDS with signs of cytokine release syndrome, which included elevation of interleukin-6, fibrinogen, D-dimer, and C-reactive protein levels [9]. The therapies (corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy) were recommended once these syndromes were observed. The choice of which therapy to use was made by physicians according to their own clinical judgment. Corticosteroids were widely included in all protocols; indeed, only 2 out of 15 hospitals did not include any corticosteroid regimen. There was a total of five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone. Dexamethasone was recommended in eight protocols with two different regimens: 20 mg (5/8, 62.5%) or 40 mg (3/8, 37.5%) daily. Methylprednisolone was included in 13 protocols with 2 different regimens: 125–250 mg (8/13, 61.5%) or 1 mg/kg (5/13, 38.5%) daily. Only one protocol included prednisone with a single regimen of 40 mg daily. The duration of treatment varied from 3 to 10 days, depending on the patient’s clinical condition. Tocilizumab was recommended in all protocols with the same dosage (400 or 600 mg) according to body weight. Anakinra was included in seven protocols with six different regimens. Immunoglobulins were included as possible therapy in three protocols. In six protocols, other optional therapies were included, such as sarilumab, baricitinib, colchicine, ciclosporin A, sirolimus, tacrolimus, and vitamin D, according to clinical trials. Dosage and durations of corticosteroids, anticytokine or immunomodulatory agents, and immunoglobulin therapy are shown in Table 3.\nAll protocols included anticoagulant treatment (low-molecular-weight heparin as the first option and unfractionated heparin as an alternative) and recommended prophylactic heparin during hospitalization. In 8 of the 15 COVID-19 protocols (53.3%), the dose of prophylactic low-molecular-weight heparin was increased if there was a high risk of thrombosis (severe COVID-19 with evidence of cytokine release syndrome, previous venous thromboembolism or acute ischemic artery disease, or D-dimer \u003e3000 ng/mL). In five protocols (33.3%), heparin was increased to therapeutic doses if the condition was critical or if there was a progressive increase in D-dimer levels. All protocols included therapeutic heparin if there was evidence of venous thromboembolism. At discharge, prophylactic heparin was recommended if D-dimer \u003e1500-3000 ng/dL for 7 days or during the time of the expected severe immobilization in seven protocols (46.6%). Adjustments of heparin doses were indicated in the respective protocols.\nSupportive care, hospital circuits, ward organization, and care planning were included in all protocols. Drug side effects (including follow-up electrocardiogram for QT prolongation), interactions, nonrecommended treatment, or recommendation for other drugs were included in 11 protocols (73,3%), and discharge recommendations in 12 (80%)."}