Development of Evidence-Based COVID-19 Management Guidelines for Local Context: The Methodological Challenges

Table 2

Description of study characteristics: cross-sectional and cohort studies.

S. no.	Author, country	Title	Study duration in days	Intervention group	Comparator group	Concomitant group	Outcome measures	Outcome measures applicable to this review
1	Stessel et al., Belgium	Impact of implementation of an individualized thromboprophylaxis protocol in critically ill ICU patients with COVID-19: A longitudinal controlled before-after study.	52	Nadroparin calcium 2850 IU (preimplementation of protocol)	Nadroparin calcium 2850 IU (postimplementation of protocol)	—	(i) One-month mortality; (ii) Two-week and three-week mortality; (iii) Hospital length of stay	(i) One-month mortality; (ii) Two-week and three-week mortality; (iii) Hospital length of stay
2	Jonmarker et al., Sweden	Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients	56	(i) Tinzaparin or dalteparin low (2500–4500 IU tinzaparin or 2500–5000 IU dalteparin); (ii) Tinzaparin or dalteparin medium (> 4500 IU but < 175 IU/kilogram, kg, of bodyweight tinzaparin or > 5000 IU but < 200 IU/kg of bodyweight dalteparin); (iii) High dose (≥ 175 IU/kg of bodyweight tinzaparin or ≥ 200 IU/kg of bodyweight dalteparin)	—	—	(i) 28 days mortality; (ii) ICU stay; (iii) Thromboembolic events	(i) 28 days mortality; (ii) ICU stay; (iii) Thromboembolic events
3	Salton et al., Italy	Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia	58	Methylprednisolone loading dose of 80 mg intravenously, followed by an infusion of 80 mg/d in 240 ml of normal saline at 10 ml/h for at least 8 days	—	Standard of care (antibiotics, antivirals, vasopressors, and renal replacement therapy)	(i) Mortality; (ii) Transfer to intensive care unit; (iii) Invasive mechanical ventilation	(i) Mortality; (ii) Transfer to intensive care unit; (iii) Invasive mechanical ventilation
4	Mutair et al., Saudi Arabia	Clinical, epidemiological, and laboratory characteristics of mild-to-moderate COVID-19 patients in Saudi Arabia: An observational cohort study	31	Hydroxychloroquine in mild cases	Hydroxychloroquine in moderate cases	(i) Hydroxychloroquine; (ii) Azithromycin; (i) Oseltamivir; (iii) Vitamin C; (iv) Vitamin E; (v) Ceftriaxone; (vi) Enoxaparin	(i) Days of hospitalization; (ii) SARS-CoV-2 PCR negative; (iii) Treatment outcomes	(i) Days of hospitalization; (ii) SARS-CoV-2 PCR negative; (iii) Treatment outcomes
5	Annie et al., the United States	Hydroxychloroquine in hospitalized patients with COVID-19: real-world experience assessing mortality	116	(i) Hydroxychloroquine alone; (ii) Hydroxychloroquine plus azithromycin	—	—	Mortality	Mortality
6	Arshad et al., the United States	Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19	—	(i) Hydroxychloroquine alone; (ii) Azithromycin alone 500 mg once daily on day 1 followed by 250 mg once daily for the next 4 days.; (iii) Hydroxychloroquine plus azithromycin	Neither treatment	(i) Steroid; (ii) Tocilizumab	(i) Mortality; (ii) Hospital length of stay in days.	(i) Mortality; (ii) Hospital length of stay in days
7	Ashinyo et al., Ghana	Clinical characteristics, treatment regimen, and duration of hospitalization among COVID-19 patients in Ghana: A retrospective cohort study	93	(i) Chloroquine + hydroxychloroquine; (ii) Hydroxychloroquine + azithromycin; (iii) Hydroxychloroquine only; (iv) Azithromycin only; (v) Supportive treatment	—	—	Duration of hospitalization	Duration of hospitalization
8	Ayerbe et al., Spain	The association between treatment with heparin and survival in patients with COVID-19	55	(i) Heparin	—	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Steroids; (iv) Tocilizumab; (v) Lopinavir with ritonavir; (vi) Oseltamivir	Mortality	Mortality
9	Ayerbe et al., Spain	The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients	55	Hydroxychloroquine was dosed as 400 mg twice daily the first day, followed by 200 mg twice daily for 4–6 days.	—	(i) Azithromycin; (ii) Steroids; (iii) Heparin; (iv) Tocilizumab; (v) Lopinavir with ritonavir; (vi) Oseltamivir	Mortality	Mortality
10	Bartoletti et al., Italy	Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: A multicentre study	130	Corticosteroid ≥0.5 mg/kg of prednisone	—	(i) Hydroxychloroquine; (ii) Lopinavir/ritonavir; (iii) Darunavir/ritonavir; (iv) Darunavir/cobicistat; (v) Remdesivir; (vi) Low-molecular-weight heparin; (vii) Other standard of care	Mortality	Mortality
11	Camprubí et al., Spain	Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients	21	Ivermectin 200 μg/kg for 8–18 days	No ivermectin	(i) Tocilizumab; (ii) Steroids; (iii) Anakinra; (iv) Remdesivir; (v) Lopinavir/ritonavir; (vi) Hydroxychloroquine; (vii) Azithromycin; (viii) Beta-interferon; (ix) Hydroxychloroquine; (x) Azithromycin	Severe adverse events	Severe adverse events
12	Canoglu et al., Turkey	Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection	51	Heparin prophylactic dose LMWH (0.5 mg/kg twice daily)	Heparin therapeutic dose LMWH (1 mg/kg twice daily)	(i) Favipiravir; (ii) Lopinavir-ritonavir; (iii) Supportive treatment	(i) Mortality; (ii) ICU admission; (iii) Hospital stay	(i) Mortality; (ii) ICU admission; (iii) Hospital stay
13	Catteau et al., Belgium	Low-dose hydroxychloroquine therapy and mortality in hospitalized patients with COVID-19: A nationwide observational study of 8075 participants	72	Hydroxychloroquine 2400 mg over 5 days	No hydroxychloroquine	(i) Lopinavir/ritonavir; (ii) Hydroxychloroquine; (iii) Tocilizumab; (iv) Remdesivir; (v) Macrolides; (vi) Anakinra	(i) Mortality; (ii) Hospital stay; (iii) Invasive mechanical ventilation; (iv) Admission to ICU	(i) Mortality; (ii) Hospital stay; (iii) Invasive mechanical ventilation; (iv) Admission to ICU
14	Ana Fernández-Cruz, Spain	A retrospective controlled cohort study of the impact of glucocorticoid treatment in SARS-CoV-2 infection mortality	35	Steroid	No steroid	(i) Hydroxychloroquine; (ii) Lopinavir-ritonavir; (iii) Azithromycin; (iv) Interferon; (v) Tocilizumab; (vi) Anakinra	Mortality	Mortality
15	Freedberg et al., the United States	Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: A propensity score matched retrospective cohort study	56	Famotidine	No famotidine	—	Mortality or intubation	Mortality or intubation
16	Geleris et al., United States	Observational study of hydroxychloroquine in hospitalized patients with COVID-19	50	Hydroxychloroquine 600 mg twice on day 1 and then 400 mg daily for a median of 5 days	No hydroxychloroquine	(i) Systemic glucocorticoid; (ii) Anticoagulant or warfarin; (iii) Azithromycin; (iv) Antibiotic agent; (v) Tocilizumab; (vi) Remdesivir	Intubation or death	Intubation or death
17	Berry et al., United States	Hydroxychloroquine and tocilizumab therapy in COVID-19 patients: An observational study	66	(i) Hydroxychloroquine 800 mg on day 1 and 400 mg on days 2–5, followed by 200 mg TID; (ii) Hydroxychloroquine in combination with azithromycin; (iii) Tocilizumab first dose 400 mg, followed by 800 mg	(i) Neither hydroxychloroquine/azithromycin; (ii) Azithromycin alone; (iii) No tocilizumab	For patients in tocilizumab/no tocilizumab group: (i) Steroid; (ii) Hydroxychloroquine alone; (iii) Azithromycin alone; (iv) Azithromycin plus hydroxychloroquine	(i) Mortality; (ii) Adverse drug events	(i) Mortality; (ii) Adverse drug events
18	Karolyi et al., Austria	Hydroxychloroquine versus lopinavir/ritonavir in severe COVID-19 patients	57	Hydroxychloroquine loading dose of 400 mg twice on the first day, followed by 200 mg twice daily	Lopinavir/ritonavir 400 mg/100 mg administered twice daily	Concomitant antibiotic	(i) In-hospital mortality; (ii) Intensive care unit (ICU) admission; (iii) Length of stay; (iv) PCR (polymerase chain reaction) negativity; (v) Side effects of treatment	(i) In-hospital mortality; (ii) Intensive care unit (ICU) admission; (iii) Length of stay; (iv) PCR (polymerase chain reaction) negativity; (v) Side effects of treatment
19	Kirenga et al., Uganda	Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda	—	Hydroxychloroquine	No hydroxychloroquine	(i) Antibiotics (azithromycin, ampicillin/cloxacillin combination, and augmentin); (ii) Vitamin C	(i) Admission to ICU; (ii) Mechanical ventilation; (iii) Death; (iv) Negative reverse transcriptase PCR (RT-PCR) tests; (v) Length of hospitalization	(i) Admission to ICU; (ii) Mechanical ventilation; (iii) Death; (iv) Negative reverse transcriptase PCR (RT-PCR) tests; (v) Length of hospitalization
20	Lagier et al., France	Outcomes of 3737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis	56	(i) Azithromycin + hydroxychloroquine >3 days (hydroxychloroquine 200 mg of oral hydroxychloroquine, 3 times daily for 10 days and 500 mg of oral azithromycin on day 1 followed by 250 mg daily for the next 4 days); (ii) Other treatment (azithromycin-hydroxychloroquine for at least 3 days); (iii) Azithromycin + hydroxychloroquine <3 days; (iv) Hydroxychloroquine alone; (v) Azithromycin alone; (vi) No azithromycin and hydroxychloroquine	—	—	(i) Death; (ii) Transfer to the intensive care unit (ICU); (iii) ≥10 days of hospitalization; (iv) Viral shedding	(i) Death; (ii) Transfer to the intensive care unit (ICU); (iii) ≥10 days of hospitalization; (iv) Viral shedding
21	Albertini et al., France	Observational study on off-label use of tocilizumab in patients with severe COVID-19	16	Tocilizumab 8 mg/kg	No tocilizumab	(i) Hydroxychloroquine; (ii) Azithromycin	(i) Mortality; (ii) Mechanical ventilation; (iii) Length of stay; (iv) Adverse events	(i) Mortality; (ii) Mechanical ventilation; (iii) Length of stay; (iv) Adverse events
22	Almazrou et al., Saudi Arabia	Comparing the impact of hydroxychloroquine-based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study	20	Hydroxychloroquine	Standard care; (i) Oseltamivir; (ii) Azithromycin; (iii) Levofloxacin; (iv) Hydroxychloroquine; (v) Ceftriaxone; (vi) Piperacillin/tazobactam; (vii) Vancomycin; (viii) Cefuroxime; (ix) Doxycycline; (x) Tazocin; (xi) Moxifloxacin	—	(i) Hospital length of stay; (ii) Time in ICU, days; (iii) ICU admission; (iv) Mechanical ventilation	(i) Hospital length of stay; (ii) Time in ICU, days; (iii) ICU admission; (iv) Mechanical ventilation
23	Billet et al., the United States	Anticoagulation in COVID-19: effect of enoxaparin, heparin, and apixaban on mortality	30	(i) Apixaban prophylaxis; (ii) Apixaban full therapy; (iii) Enoxaparin prophylaxis; (iv) Enoxaparin full therapy; (v) Unfractionated Heparin standard prophylaxis; (vi) Unfractionated heparin high prophylaxis; (vii) Unfractionated heparin full therapy	—	—	(i) Mortality; (ii) Respiratory support	(i) Mortality; (ii) Respiratory support
24	Capra et al., Italy	Impact of low-dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia	—	Tocilizumab	No tocilizumab	Standard care; (i) Hydroxychloroquine 400 mg; (ii) Lopinavir 800 mg; (iii) Ritonavir 200 mg	Mortality	Mortality
25	Mario Fernández‐Ruiz et al., Spain	Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study	—	Tocilizumab	—	(i) Hydroxychloroquine; (ii) Lopinavir; (iii) Ritonavir; (iv) Azithromycin; (v) Interferon; (vi) Corticosteroids	(i) Clinical improvement at day 7; (ii) Clinical improvement at day 14	(i) Clinical improvement at day 7; (ii) Clinical improvement at day 14
26	Gupta et al., the United States	Association between early treatment with tocilizumab and mortality among critically ill patients with COVID-19	122	Tocilizumab patients received tocilizumab within 2 days of ICU admission	Tocilizumab patients did not receive tocilizumab within 2 days of ICU admission	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Corticosteroid; (iv) Anticoagulation	(i) Mortality; (ii) Adverse event	(i) Mortality; (ii) Adverse event
27	Kaminski et al., the United States	Tocilizumab therapy for COVID-19: A comparison of subcutaneous and intravenous therapies	54	Tocilizumab, 400 mg IV	Tocilizumab, subcutaneous dose of 324 mg (given as two simultaneous doses of 162 mg)	(i) Hydroxychloroquine 400 mg twice for one day, followed by 200 mg twice a day for additional 4 days plus azithromycin 500 mg once, followed by 250 mg oral once daily for additional 4 days.; (ii) Tocilizumab therapy; (iii) Corticosteroids for 3–5 days	(i) Survival rate; (ii) Ventilatory status	(i) Survival rate; (ii) Ventilatory status
28	Kim et al., Korea	Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild-to-moderate coronavirus disease 2019	44	Lopinavir-ritonavir 400 and 100 mg twice daily	Hydroxychloroquine 400 mg once daily	(i) Antibiotic agent; (ii) Glucocorticoid; (iii) IV immunoglobulin	(i) Time to negative conversion of viral RNA; (ii) Time to clinical improvement; (iii) Adverse events	(i) Time to negative conversion of viral RNA; (ii) Time to clinical improvement; (iii) Adverse events
29	Lammers et al., Netherlands	Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients	—	Hydroxychloroquine on day 1, 400 mg, and 400 mg after 12 hours, 200 mg BID on days 2–5	Chloroquine on 1st day 600 mg and 300 mg after 12 h, 300 mg BID on days 2–5	Azithromycin	(i) Death; (ii) Transfer to the intensive care unit (ICU)	(i) Death; (ii) Transfer to the intensive care unit (ICU)
30	Lauriola et al., Italy	Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in patients with COVID-19	—	(i) Azithromycin and hydroxychloroquine (hydroxychloroquine dose of 200 mg TID (alone or in combination) and azithromycin 500 mg QD for 10 days); (ii) Hydroxychloroquine 200 mg TID	No treatment (standard care not specified)	—	Mortality	Mortality
31	Lee et al., the United States	Remdesivir for the treatment of severe COVID-19: A community hospital’s experience	111	Remdesivir 200 mg loading dose on day 1, followed by a 100 mg daily on days 2–5	—	(i) Antibiotics; (ii) Convalescent plasma; (iii) Dexamethasone	(i) Mortality; (ii) Length of stay; (iii) ICU admission	(i) Mortality; (ii) Length of stay; (iii) ICU admission
32	Yiming Li et al., China	Corticosteroid therapy in critically ill patients with COVID-19: A multicenter, retrospective study	62	Corticosteroids	No corticosteroids	—	(i) 90 days mortality; (ii) Viral clearance	(i) 90 days mortality; (ii) Viral clearance
33	Liu et al., China	Clinical characteristics and corticosteroids application of different clinical types in patients with coronavirus disease 2019	121	(i) Corticosteroid; (ii) Methylprednisolone (1-2) mg/kg day general type, 1–5 mg/kg day severe type, and 1–4 mg/kg day critical type	No corticosteroids	(i) Interferon-α (IFN-α); (ii) Lopinavir/ritonavir	(i) Discharges; (ii) Mechanical ventilation; (iii) Intensive care unit (ICU) admission; (iv) Mortality	(i) Discharges; (ii) Mechanical ventilation; (iii) Intensive care unit (ICU) admission; (iv) Mortality
34	Gautret et al., France	Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a 6-day follow-up: A pilot observational study	—	Hydroxychloroquine (200 mg of oral TID for 10 days) and azithromycin (500 mg on day 1 followed by 250 mg per day for 4 days)	—	—	(i) Requiring oxygen therapy or transfer to the ICU after at least three days of treatment; (ii) Length of stay in the infectious diseases ward; (iii) Contagiousness as assessed by PCR and culture	(i) Requiring oxygen therapy or transfer to the ICU after at least three days of treatment; (ii) Length of stay in the infectious diseases ward; (iii) Contagiousness as assessed by PCR and culture
35	Yu et al., China	Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19	—	Hydroxychloroquine oral 200 mg BID for 7–10 days	Nonhydroxychloroquine	(i) Lopinavir and ritonavir; (ii) Ribavirin; (iii) Intravenous immunoglobulin	(i) Mortality; (ii) Length of stay	(i) Mortality; (ii) Length of stay
36	Guaraldi et al., Italy	Tocilizumab in patients with severe COVID-19: A retrospective cohort study	—	(i) Tocilizumab 8 mg/kg IV (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (i.e., 324 mg in total); (ii) Hydroxychloroquine; (iii) Azithromycin; (iv) Antiretrovirals; (v) Low-molecular-weight heparin	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Antiretrovirals; (iv) Low-molecular-weight heparin; (v) Lopinavir-ritonavir	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Antiretrovirals; (iv) Low-molecular-weight heparin; (v) Lopinavir-ritonavir	(i) Death; (ii) Invasive mechanical ventilation	(i) Death; (ii) Invasive mechanical ventilation
37	Grein et al., multicenter	Compassionate use of remdesivir for patients with severe COVID-19	—	Remdesivir loading dose of 200 mg intravenously on day 1 plus 100 mg daily for the following 9 days	—	Supportive care	(i) Clinical improvement; (ii) Changes in oxygen support requirements; (iii) Adverse events; (iv) Death	(i) Clinical improvement; (ii) Changes in oxygen support requirements; (iii) Adverse events; (iv) Death
38	Alexis K. Okoh et al., the United States	Tocilizumab use in COVID-19 associated pneumonia	61	Tocilizumab 8 mg/kg IV (maximum: 800 mg/dose)	No tocilizumab	Standard of care	(i) Deescalation in oxygen therapy; (ii) In-hospital death; (iii) Septic shock; (iv) Acute kidney injury (AKI) requiring hemodialysis	(i) Deescalation in oxygen therapy; (ii) In-hospital death; (iii) Acute kidney injury (AKI) requiring hemodialysis
39	Shao et al., China	Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: A multicenter retrospective cohort study	122	IVIG 0.1–0.5 g/kg per day	Non-IVIG	—	(i) 28 days mortality; (ii) 60 days mortality; (iii) In‐hospital days; (iv) Total course of disease	(i) 28 days mortality; (ii) 60 days mortality; (iii) In‐hospital days
40	Kewan et al., the United States	Tocilizumab for treatment of patients with severe COVID-19: A retrospective cohort study	61	Tocilizumab 8 mg/kg and received 400 mg tocilizumab as a 60 min single intravenous infusion	No tocilizumab	(i) Hydroxychloroquine with a loading dose of 400 mg twice daily followed by 200 mg BID for 5 days; (ii) Azithromycin 500 mg per day for 5 days; (iii) Steroid	(i) Intubated patients’ improvement in oxygen support; (ii) Noninvasive oxygen support improvement in oxygen support; (iii) Clinical improvement among patients required mechanical ventilation; (iv) Length of stay in hospital; (v) Mortality	(i) Intubated patients’ improvement in oxygen support; (ii) Noninvasive oxygen support improvement in oxygen support; (iii) Clinical improvement among patients required mechanical ventilation; (iv) Length of stay in hospital; (v) Mortality
41	Ramiro et al., Netherlands	Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19 associated cytokine storm syndrome: results of the CHIC study	92	(i) Methylprednisolone 250 mg intravenously on day 1, followed by MP 80 mg intravenously on days 2–5; (ii) Tocilizumab single dose 8mg/kg bodyweight intravenous, maximum 800 mg between day 2 and day 5	—	(i) Ceftriaxone 2 g every 24 hours for 7 days; (ii) Chloroquine 300 mg every 12 hours following a loading dose of 600 mg	(i) Clinical improvement; (ii) WHO ordinal scale; (iii) Hospital mortality; (iv) Mechanical ventilation; (v) Duration of hospitalization	(i) Clinical improvement; (ii) WHO ordinal scale; (iii) Hospital mortality; (iv) Mechanical ventilation; (v) Duration of hospitalization
42	Colaneri et al., Italy	Tocilizumab for treatment of severe COVID-19 patients: preliminary results from SMAtteo COVID-19 Registry (SMACORE)	14	Tocilizumab 8 mg/kg (up to a maximum 800 mg per dose) IV repeated 12 hours plus standard of care	Standard of care; (i) Hydroxychloroquine 200 mg BID; (ii) Azithromycin 500 mg once; (iii) Prophylactic dose of low weight heparin; (iv) Methylprednisolone (a tapered dose of 1 mg/kg up to a maximum of 80 mg) for 10 days	—	(i) ICU admission; (ii) 7 days mortality rate; (iii) Clinical and laboratory data; (iv) Days of hospitalization	(i) ICU admission; (ii) 7 days mortality rate; (iii) Days of hospitalization
43	Mather et al., the United States	Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19	80	(i) Famotidine 80 mg (range 40–160 mg) was received over a median of 4 days; (ii) Hydroxychloroquine 600 mg/day	(i) No famotidine	(i) Hydroxychloroquine, 600 mg/day; (ii) Azithromycin; (iii) Remdesivir; (iv) Corticosteroids	(i) Death; (ii) Disease severity; (iii) Mechanical ventilation	(i) Death; (ii) Mechanical ventilation
44	Million et al., France	Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France	29	Hydroxychloroquine + azithromycin: a combination of 200 mg of oral HCQ, 3 times daily for 10 days combined with 5 of AZ (500 mg on day 1 followed by 250 mg daily for the next 4 days)	Hydroxychloroquine + azithromycin early treatment, as standard care.	—	(i) Length of hospitalization; (ii) Death; (iii) Contagiousness as assessed by PCR and culture.	(i) Length of hospitalization; (i) Death; (iii) Contagiousness as assessed by PCR and culture.
45	Morrisona et al., the United States	Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab	34	(i) Tocilizumab was administered as an 8 mg/kg IV dose using actual bodyweight with a maximum dose of 800 mg. Doses were rounded to 400 mg, 600 mg, or 800 mg.; (ii) Corticosteroids; (iii) Hydroxychloroquine; (iv) Lopinavir/ritonavir with ribavirin; (v) Remdesivir	(i) Lopinavir/ritonavir with ribavirin, received as supportive care; (ii) Hydroxychloroquine, received as supportive care	—	(i) WHO ordinal scale; (ii) 28 day in-hospital survival; (iii) Duration of hospitalization	(i) WHO ordinal scale; (ii) 28 day in-hospital survival; (iii) Duration of hospitalization
46	Pasquini et al., Italy	Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU	21	Remdesivir, first dose of 200 mg IV on day 1 plus 100 mg daily from day 2 on.	No remdesivir	(i) Tocilizumab; (ii) Hydroxychloroquine; (iii) Lopinavir/ritonavir with ribavirin	Mortality	Mortality
47	Patel et al., India	Safety and efficacy of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus 2 pneumonia: A retrospective cohort study	31	Tocilizumab dosed at 8 mg/kg, up to a maximum dose of 800 mg	—	(i) Hydroxychloroquine. 400 mg/day for 5 days after a loading dose of 400 mg twice a day on 1st day.; (ii) Azithromycin 500 mg/day for 5 days.; (iii) IV ceftriaxone 1 g per day for 5 days.; (iv) Anticoagulation: low-molecular-weight heparin or unfractionated heparin infusion was used if the patient’s D-dimer was >1000 ng/ml.; (v) Methylprednisolone: some patients also received a single dose of 80 mg IV methylprednisolone before receiving tocilizumab.	(i) Mortality; (ii) Admission to the intensive care unit (ICU) with invasive mechanical ventilation or death; (iii) Hospital stay	(i) Mortality; (ii) Admission to the intensive care unit (ICU) with invasive mechanical ventilation or death; (iii) Hospital stay
48	Rahmani et al., Iran	Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir	58	Hydroxychloroquine + atazanavir/ritonavir has 400 mg BD on the first day and then 200 mg. 300/100 mg daily was started within 24 h of the hospital admission for all patients	(i) ARB; (ii) Metformin; (iii) Aspirin; (iv) Beta-blockers; (v) Insulin; (vi) Corticosteroids; (vii) Hydroxychloroquine; (viii) Immunosuppressants; (ix) NSAIDs; (x) Methotrexate; (xi) ACEI; (xii) Azathioprine; (xiii) Sulfasalazine	(i) Interferon; (ii) Ribavirin; (iii) Corticosteroid; (iv) IVIG; (v) Vitamin C; (vi) Antibiotics	(i) 28 days mortality; (ii) Hospital stay; (iii) ICU stays; (iv) Rate of ICU admissions and intubation	(i) 28 days mortality; (ii) 56 days mortality; (iii) Hospital stay; (iv) Rate of ICU admissions and intubation
49	Rodrı’guez-MolineroI et al., Spain	Observational study of azithromycin in hospitalized patients with COVID-19	52	Azithromycin prescribed at a dose of 500 mg on the first day (oral or intravenous), followed by 250 mg daily, until completing 5 days of treatment.	Standard of care	(i) Azithromycin; (ii) Tocilizumab; (iii) Methylprednisolone; (iv) Dexamethasone	(i) Hospital stays; (ii) Mortality; (iii) Oxygen requirement	(i) Hospital stays; (ii) Mortality; (iii) Oxygen requirement
50	Rosenberg et al., the United States	Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State	19	(i) Hydroxychloroquine with or without azithromycin; (ii) Azithromycin	—	—	(i) In-hospital mortality; (ii) Cardiac arrest and abnormal electrocardiographic (ECG) findings (defined as arrhythmia or prolonged QT fraction); (iii) Length of stay	(i) In-hospital mortality; (ii) Length of stay
51	Rubio-Rivasa et al., Spain	Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness	22	Tocilizumab as a single IV infusion at a dose of 400 mg (weight <80 kg) or 600 mg (weight >80 kg) or using methylprednisolone at doses ranging from 0.5 mg/kg/d to 250 mg IV in 3 pulses	—	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Lopinavir/ritonavir; (iv) Remdesivir; (v) Prophylactic anticoagulation therapy; (vi) Subcutaneous interferon beta-1b 0.25 mg/48 h.	(i) In-hospital mortality	(i) In-hospital mortality
52	Shi et al., China	Evaluation of antiviral therapies for coronavirus disease 2019 pneumonia in Shanghai, China	19	(i) Arbidol group 200 mg, three times/day; (ii) Lopinavir/ritonavir group two tablets, two times/day; (iii) Arbidol + lopinavir/ritonavir group; (iv) Interferon group 100 000 U/kg, two times/day; (v) Interferon + lopinavir/ritonavir group; (vi) Interferon + darunavir group one tablet, one time/day.	—	—	(i) Improvements in pulmonary involvement; (ii) Length of hospital stay	(i) Pneumonia resolution after treatment; (ii) Length of hospital stay
53	Tang et al., China	Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy	34	Unfractionated heparin or low-molecular-weight heparin (LMWH) for 7 days or longer.	No heparin or less than 7 days	—	28 days mortality	28 days mortality
54	Tong et al., China	Ribavirin therapy for severe COVID-19: a retrospective cohort study	60	Intravenous ribavirin 500 mg every 12 h	—	Corticosteroids	(i) Mortality; (ii) Negative conversion time for the SARS-CoV-2 RT-PCR test	(i) Mortality; (ii) Negative conversion time for the SARS-CoV-2 RT-PCR test
55	Toniati et al., Italy	Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single-center study of 100 patients in Brescia, Italy	12	(i) Tocilizumab. at a dosage of 8 mg/kg (max 800 mg) by two consecutive intravenous infusions 12 h apart.; (ii) Lopinavir + ritonavir 400 mg and 100 mg twice a day.; (iii) Remdesivir; (iv) Azithromycin; (v) Ceftriaxone; (vi) Piperacillin/tazobactam; (vii) Hydroxychloroquine 400 mg/day; (viii) Dexamethasone 20 mg/day	—	—	Improvement in acute respiratory failure	Improvement in acute respiratory failure
56	Tsai et al., China	Successful treatment of 28 patients with coronavirus disease 2019 at a medical center in Taiwan	154	(i) Hydroxychloroquine + azithromycin + ceftriaxone + teicoplanin; (ii) Hydroxychloroquine + azithromycin + ceftriaxone; (iii) Hydroxychloroquine + azithromycin; (iv) Hydroxychloroquine + ceftriaxone; (v) Hydroxychloroquine, azithromycin	—	—	None	None
57	Vu et al., Florida	Effects of tocilizumab in COVID-19 patients: A cohort study	19	Tocilizumab 400 mg (30–100 kg) and 600 mg (> 100 kg)	—	(i) Hydroxychloroquine; (ii) Methylprednisolone; (iii) Intravenous immunoglobulin; (iv) Convalescent plasma	(i) WHO ordinal scale; (ii) Length of stay; (iii) Mortality	(i) WHO ordinal scale; (ii) Mortality; (iii) Length of stay
58	Wu et al., China	Systemic corticosteroids and mortality in severe and critical COVID-19 patients in Wuhan, China	81	(i) Corticosteroid; (ii) Hydrocortisone 5 mg; (iii) Methylprednisolone 1 mg; (iv) Dexamethasone 0.1875 mg	No corticosteroid	—	(i) Mortality; (ii) Hospital stays	(i) Mortality; (ii) Hospital stays
59	Yan et al., China	Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalized noncritically ill patients with SARS-CoV-2 infection	39	(i) Lopinavir/ritonavir 400 mg and 100 mg, orally twice daily; (ii) Corticosteroid therapy; (iii) Antibiotics; (iv) High-flow nasal cannula oxygen therapy; (v) Noninvasive mechanical ventilation; (vi) Invasive mechanical ventilation	—	—	(i) Length of stay; (ii) Viral shedding days	(i) Length of stay; (ii) Viral shedding days
60	Yang et al., China	The role of methylprednisolone on preventing disease progression for hospitalized patients with severe COVID‐19	67	Methylprednisolone 50–80 mg/d	(i) Nonmethylprednisolone; (ii) Oseltamivir; (iii) Arbidol hydrochloride; (iv) Lopinavir/ritonavir; (v) Darunavir and/cobicistat	—	(i) Progression to critical illness; (ii) Deaths	(i) Progression to critical illness; (ii) Deaths
61	You et al., China	The use of methylprednisolone in COVID-19 patients: A propensity score matched retrospective cohort study	60	Methylprednisolone 40 mg once or twice per day within 48 hours of admission for one week.	Nonmethylprednisolone	—	(i) Hospital mortality; (ii) Positive nucleic acid test to turn negative; (iii) Length of hospital stay; (iv) Oxygen requirement	(i) Hospital mortality; (ii) Positive nucleic acid test to turn negative; (iii) Length of hospital stay; (iv) Oxygen requirement
62	Yuan et al., China	Effects of corticosteroid treatment for nonsevere COVID-19 pneumonia: A propensity score-based analysis	37	(i) Corticosteroid; (ii) Methylprednisolone	Noncorticosteroid group	(i) Ribavirin; (ii) Oseltamivir; (iii) Arbidol; (iv) Lopinavir/ritonavir; (v) Interferon	(i) Progressed to severe cases; (ii) Secondary infection; (iii) Hospital stays; (iv) Duration of viral shedding; (v) Fever time	(i) Progressed to severe cases; (ii) Hospital stay; (iii) Duration of viral shedding
63	Mushtaq et al., Pakistan	Outcome of COVID-19 patients with use of tocilizumab: A single-center experience	62	Tocilizumab 4–8 mg/kg.	—	(i) Azithromycin; (ii) Ceftriaxone or piperacillin/tazobactam; (iii) Methylprednisolone; (iv) Hydroxychloroquine	(i) Mortality; (ii) Length of hospital stay; (iii) Weaning from a mechanical ventilator, weaning from oxygen support, improvement in laboratory parameters	(i) Mortality; (ii) Length of hospital stay; (iii) Weaning from a mechanical ventilator, weaning from oxygen support, improvement in laboratory parameters
64	Yan Zuo et al., China	Lopinavir/ritonavir and interferon combination therapy may help shorten the duration of viral shedding in patients with COVID‐19: A retrospective study in two designated hospitals in Anhui, China	56	(i) Corticosteroid; (ii) Lopinavir/ritonavir; (iii) Chloroquine; (iv) Ribavirin; (v) IFN‐α; (vi) Arbidol; (vii) Intravenous immunoglobulin; (viii) Traditional Chinese medicine	—	—	Length of stay	Length of stay
65	Yu et al., China	COVID‐19 patients benefit from early antiviral treatment: A comparative, retrospective study	27	(i) Arbidol; (ii) Interferon; (iii) Oseltamivir; (iv) Ribavirin; (v) Ganciclovir; (vi) Antibiotic treatment; (vii) Antifungal treatment; (viii) Oxygen therapy; (ix) Glucocorticoids; (x) Immunotherapy	—	—	(i) Time from illness onset to be confirmed by SARS‐Cov‐2 RNA detection; (ii) Time from illness onset to initiation of antiviral treatment; (iii) Duration of total antiviral medication during the illness; (iv) Time from illness onset to SARS‐CoV‐2 negative	(i) Time from illness onset to be confirmed by SARS‐Cov‐2 RNA detection; (ii) Time from illness onset to SARS‐CoV‐2 negative
66	Llitjos et al., France	High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients	9	Prophylactic anticoagulation	Therapeutic anticoagulation 0.3–0.7 U/ml	—	(i) Acute respiratory distress syndrome; (ii) Acute kidney injury; (iii) Liver dysfunction; (iv) Death	(i) Acute respiratory distress syndrome; (ii) Death
67	Borie et al., France	Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study	42	(i) Corticosteroid ± anakinra; (ii) Methylprednisolone 120 mg (daily dose) on three consecutive days; (iii) Glucocorticoid	Thrombosis prophylaxis with LMWH. From February 15 to March 27, 2020	(i) Lopinavir-ritonavir; (ii) Hydroxychloroquine; (iii) Ivermectin, 12–15 mg; (iv) Remdesivir; (v) Thrombosis prophylaxis with LMWH; (vi) Tocilizumab; (vii) Corticosteroids, 120 mg; (viii) Anakinra, 100 mg anakinra daily was added subcutaneously for ≤5days	(i) Death; (ii) Invasive mechanical ventilation requirement within 15 days	(i) Death; (ii) Invasive mechanical ventilation requirement within 15 days
68	Majmundar et al., the United States	Efficacy of corticosteroids in nonintensive care unit patients with COVID-19 pneumonia from the New York metropolitan region	57	(i) Corticosteroids; (ii) Methylprednisolone; (iii) Prednisone; (iv) Dexamethasone	Noncorticosteroids	(i) Hydrocortisone; (ii) Tocilizumab; (iii) Enoxaparin therapeutic dose	(i) Intensive care unit (ICU) transfer; (ii) ICU transfer; (iii) Intubation; (iv) Death; (v) Discharge; (vi) Length of stay	(i) Intensive care unit (ICU) transfer; (ii) Intubation; (iii) Death; (iv) Length of stay
69	Martínez-Sanz et al., Spain	Effects of tocilizumab on mortality in hospitalized patients with COVID-19: A multicenter cohort study	24	Tocilizumab	Standard of care	(i) Corticosteroids; (ii) Hydroxychloroquine; (iii) Azithromycin; (iv) Lopinavir/ritonavir	(i) Non-ICU length of stay (days); (ii) ICU admission; (iii) ICU length of stay (days); (iv) Overall mortality; (v) ICU mortality; (vi) Non-ICU mortality; (vii) ICU or mortality	(i) Non-ICU length of stay (days); (ii) ICU length of stay (days); (iii) Overall mortality; (iv) ICU mortality; (v) Non-ICU mortality; (vi) ICU or mortality
70	Menzella et al., Italy	Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation	70	(i) Tocilizumab + standard therapy; (ii) Hydroxychloroquine; (iii) Antivirals (lopinavir/ritonavir or darunavir/cobicistat); (iv) Anticoagulants (full dosage); (v) Steroids (methylprednisolone 0.5–1 mg/kg/die)	(i) Standard therapy	(i) Hydroxychloroquine; (ii) Antivirals (lopinavir/ritonavir or darunavir/cobicistat); (iii) Anticoagulants (full dosage); (iv) Steroids (methylprednisolone 0.5–1 mg/kg/die)	(i) Intubation/death; (ii) Death	(i) Intubation/death; (ii) Death
71	Mikulska et al, Italy	Tocilizumab and steroid treatment in patients with COVID-19 pneumonia	—	(i) Tocilizumab. 8 mg/kg (maximum 800 mg); (ii) Methylprednisolone. 1 mg/kg for 5 days intravenously, then 0.5 mg/kg for 5 days; (iii)Standard of care	Standard of care	(i) Hydroxychloroquine. 400 mg bid; (ii) Darunavir/ritonavir. 800/100 qd; (iii) Low-molecular-weight heparin prophylaxis	(i) Time to failure, defined as intubation and mechanical ventilation or death; (ii) Overall survival; (iii) Time of hospitalization for the comparison between tocilizumab/methylprednisolone/SOC	(i) Time to failure, defined as intubation and mechanical ventilation or death; (ii) Overall survival; (iii) Time of hospitalization for the comparison between tocilizumab/methylprednisolone/SOC
72	Monreal et al., Spain	High versus standard doses of corticosteroids in severe COVID-19: A retrospective cohort study	61	High doses of corticosteroids: short-term pulse therapy of methylprednisolone-equivalent dosages from 250 to 1000 mg/day during one or more consecutive days.	Standard doses of corticosteroids. Methylprednisolone-equivalent dosages ranging from 0.5 to 1.5 mg/kg/day.	—	(i) Mortality; (ii) A combined variable of need for mechanical or noninvasive MV and death.; (iii) The development of severe ARDS, according to the Berlin definition	(i) Mortality; (ii) A combined variable of need for mechanical or noninvasive MV and death
73	Pérez et al., Spain	Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study	52	Tocilizumab: initial 600 mg, with a second or third dose (400 mg) in case of persistent or progressive disease	Not received tocilizumab	(i) Hydroxychloroquine; (ii) Lopinavir/ritonavir; (iii) Azithromycin.	(i) All-cause mortality (either in-hospital or after discharge) and associated factors.; (ii) The impact of an early clinical response to tocilizumab in hospital and ICU stay.; (iii) Evaluate safety of tocilizumab therapy.	(i) All-cause mortality (either in-hospital or after discharge) and associated factors.; (ii) The impact of an early clinical response to tocilizumab in hospital and ICU stay.; (iii) Evaluate safety of tocilizumab therapy.
74	Nadkarni et al., the United States	Anticoagulation, bleeding, mortality, and pathology in hospitalized patients with COVID-19	61	(i) Therapeutic anticoagulation; (ii) Prophylactic anticoagulation	No anticoagulation	—	(i) Mortality; (ii) Intubation and major bleeding	(i) Mortality; (ii) Intubation and major bleeding
75	Nasir et al., Pakistan	Tocilizumab for COVID-19 acute respiratory distress syndrome: outcomes assessment using the WHO ordinal scale	121	Before tocilizumab	After tocilizumab	Concomitant steroids	(i) WHO ordinal scale; (ii) Mortality; (iii) Length of stay; (iv) Development of nosocomial infection during hospitalization.	(i) WHO ordinal scale; (ii) Mortality; (iii) Length of stay
76	Omrani et al., Qatar	Convalescent plasma for the treatment of patients with severe coronavirus disease 2019: A preliminary report	62	Convalescent plasma	Standard of care	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) lopinavir-ritonavir; (iv) Tocilizumab; (v) Methylprednisolone	(i) WHO ordinal scale; (ii) Improvement in the respiratory status; (iii) Discharged alive from ICU by study day 28; (iv) Viral clearance	(i) WHO ordinal scale; (ii) Improvement in the respiratory status; (iii) Discharged alive from ICU by study day 28; (iv)Viral clearance
77	Paccoud et al., France	Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe COVID-19 in a French university hospital	79	Hydroxychloroquine, 200 mg 3 times daily for 10 days	(i) Oxygen therapy to maintain an oxygen saturation >96%; (ii) Intravenous or oral acetaminophen; (iii) Antibiotics	—	(i) Death; (ii) Admission to an ICU; (iii) Time to death; (iv) Time to hospital discharge for a return home or in an aftercare and rehabilitation; (v) Adverse events recorded in patients receiving hydroxychloroquine treatment	(i) Death; (ii) Admission to an ICU; (iii) Adverse events recorded in the patients receiving hydroxychloroquine treatment
78	Price et al., the United States	Tocilizumab treatment for cytokine release syndrome in hospitalized patients with coronavirus disease 2019: survival and clinical outcomes	22	(i) Hydroxychloroquine; (ii) Glucocorticoids; (iii) Tocilizumab, 8 mg/kg intravenously, not to exceed 800mg;	—	—	(i) Survival; (ii) 14 days survival; (iii) Mechanical ventilation; (iv) Days mechanically ventilated; (v) Days of symptoms prior to hospitalization; (vi) Days hospitalized; (vii) Hospitalized at day 14	(i) Survival; (ii) 14 days survival; (iii) Mechanical ventilation; (iv) Days mechanically ventilated; (v) Days hospitalized; (vi) Hospitalized at day 14
79	Rodríguez-Baño et al., Spain	Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: A multicenter cohort study (SAM-COVID-19)	59	(i) Tocilizumab; (ii) Corticosteroid pulse dose; (iii) Corticosteroids intermediate-high dose; (iv) Combination therapy	No treatment	-	(i) WHO ordinal scale (ii) Death or intubation	(i) WHO ordinal scale (ii) Death or intubation
80	Roomi et al., United States	Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: single-center retrospective chart review	91	(i) Hydroxychloroquine; (ii) Tocilizumab	(i) No hydroxychloroquine; (ii) No tocilizumab	(i) Steroids; (ii) Anticoagulation	(i) Invasive mechanical ventilation; (ii) Mortality; (iii) Discharge	(i) Invasive mechanical ventilation; (ii) Mortality; (iii) Dialysis
81	Antorán et al., Spain	Combination of tocilizumab and steroids to improve mortality in patients with severe COVID-19 infection: A Spanish, multicenter, cohort study	49	Tocilizumab	No tocilizumab	(i) Hydroxychloroquine; (ii) Lopinavir/ritonavir; (iii) Azithromycin; (iv) Remdesivir; (v) Interferon; (vi) Steroids	Mortality	Mortality
82	Tortajada et al., Spain	Corticosteroids for COVID‐19 patients requiring oxygen support? Yes, but not for everyone: effect of corticosteroids on mortality and intensive care unit admission in patients with COVID‐19 according to patients’ oxygen requirements	59	(i) Corticosteroids; (ii) Methylprednisolone 250 mg iv once and 40 mg BIQ for 4 days; (iii) Dexamethasone 20 mg iv QD for 5 days, followed by 10 mg QD for 5 more days	No corticosteroids	(i) Hydroxychloroquine; (ii) Azithromycin; (iii) Lopinavir/ ritonavir; (iv) Tocilizumab; (v) Interferon beta	(i) WHO ordinal scale.; (ii) Admission to ICU or in‐hospital death; (iii) Clinical improvement	(i) WHO ordinal scale.; (ii) Admission to ICU or in‐hospital death; (iii) Clinical improvement
83	Magagnoli et al., the United States	Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19	21	(i) Hydroxychloroquine; (ii) Hydroxychloroquine + azithromycin; (iii) No hydroxychloroquine	—	—	(i) Mortality; (ii) Use of mechanical ventilation	(i) Mortality; (ii) Use of mechanical ventilation
84	Joyner et al., United States	Early safety indicators of COVID-19 convalescent plasma in 5000 patients	39	Convalescent plasma	—	—	The safety of transfusion of COVID-19 convalescent plasma assessed as the incidence and relatedness of severe adverse events including death.	The safety of transfusion of COVID-19 convalescent plasma assessed as the incidence and relatedness of severe adverse events including death.
85	Rajter et al., South Florida, the United States	Use of ivermectin is associated with lower mortality in hospitalized patients with coronavirus disease 2019: The ivermectin in COVID-19 study	58	Ivermectin 200 μg/kg	No ivermectin	(i) Corticosteroid; (ii) Hydroxychloroquine; (iii) Azithromycin	(i) Mortality; (ii) Successful extubation; (iii) Length of hospital stay	(i) Mortality; (ii) Successful extubation; (iii) Length of hospital stay.
86	Hanif et al., the United States	Thrombotic complications and anticoagulation in COVID-19 pneumonia: A New York City hospital experience	31	(i) Therapeutic anticoagulation prior to admission; (ii) Therapeutic anticoagulation during the admission; (iii) Prophylactic anticoagulation only during the hospital stay; (iv) No anticoagulation	—	—	(i) Mortality; (ii) Length of stay; (iii) Intubation; (iv) Successful extubation	(i) Mortality; (ii) Length of stay; (iii) Intubation; (iv) Successful extubation
87	Duan et al., China	Effectiveness of convalescent plasma therapy in severe COVID-19 patients	30	Convalescent plasma: one dose of 200 ml of inactivated CP with neutralization activity of >1:640 was transfused into the patients within 4 h following the WHO blood transfusion protocol.	—	(i) Antiviral therapy; (ii) Other supportive care; (iii) Antibiotic treatment; (iv) Antifungal treatment; (v) Glucocorticoid; (vi) Oxygen support at the appropriate situation	(i) The safety of convalescent plasma transfusion.; (ii) The improvement of clinical symptoms and laboratory and radiological parameters within 3 days after; (iii) Convalescent plasma transfusion.	(i) The safety of convalescent plasma transfusion.; (ii) The improvement of clinical symptoms and laboratory and radiological parameters within 3 days after; (iii) Convalescent plasma transfusion.