Table 1.

Summary of questions and recommendations

Question	Recommendations
Question 1	When should a patient with COVID-19 be hospitalized?  Pending further evidence, it might be prudent not to base the decision to hospitalize or not patients with COVID-19 only on prognostic scores—weak recommendation, very low certainty of evidence  Hospitalization should be considered in patients with at least one of the following: low oxygen saturation on room air ≤ 92% at rest or partial pressure of oxygen < 60 mmHg at arterial blood gas analysis*; respiratory rate > 30 breaths /min; new onset of dyspnea at rest or during speaking; reduction of oxygen saturation on room air below 90% during walking test; high value of prognostic scores; presence of anuria, confusion, hypotension, cyanosis, and/or other medical conditions requiring hospitalization per se—best practice recommendation (based on expert opinion only) *This does not strictly apply to patients with chronic obstructive pulmonary disease or other chronic respiratory disease, in whom similar values may be well tolerated, but who nonetheless need a careful personalized evaluation for hospitalization considering the presence of a baseline respiratory disease besides COVID-19
Question 2	Which drugs should be administered to outpatients with COVID-19?  Based on available results from RCTs, we do not recommend the administration of hydroxychloroquine in outpatients with COVID-19—strong recommendation, moderate certainty of evidence  We do not recommend the use of corticosteroids in outpatients with COVID-19, unless needed for other medical reasons—best practice recommendation (based on expert opinion only)  In the absence of proven bacterial infections, the administration of antibiotics in outpatients with COVID-19 should be considered only as empirical treatment of highly suspected bacterial co-infection or superinfections—weak recommendation, very low certainty of evidence (for azithromycin); best practice recommendation for other antibiotics (based on expert opinion only) At the present time, antivirals should not be administered in outpatients with COVID-19 outside RCTs—best practice recommendation (based on expert opinion only)  The use of neutralizing monoclonal antibodies may be considered in outpatients with COVID-19 with mild/moderate diseases at risk of progression and within at most 10 days after symptoms onset—weak recommendation, low certainty of evidence Of note, there was some agreement across the panel regarding the possibility to consider colchicine for the treatment of selected subgroups of outpatients with COVID-19, provided the favorable results in patients with positive COVID-19 molecular test in the COLCORONA RCT are replicated in other studies [66]
Question 3	Should anticoagulant agents be administered to inpatients with COVID-19?  Unless contraindicated, we recommend prophylactic anticoagulation in hospitalized patients with COVID-19—strong recommendation, low certainty of evidence  Hospitalized patients with COVID-19 who were already under chronic anticoagulant therapy for well-defined indications, unless contraindicated, should continue anticoagulant treatment—best practice recommendation (based on expert opinion only)  Therapeutic anticoagulation may be considered in patients possibly at higher risk of thrombotic events (serum d-dimer levels > 2.0 μg/mL) or with high suspicion for thrombotic complications—best practice recommendation (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU
Question 4	Should systemic steroids be administered to inpatients with COVID-19?  Unless contraindicated, we recommend the use of dexamethasone at the dosage of 6 mg/day for 10 days in inpatients with COVID-19 requiring oxygen supplementation*—weak recommendation, low certainty of evidence  Methylprednisolone at the dosage of 0.5 mg/kg twice daily for at least 5 days could be considered in inpatients with COVID-19 requiring oxygen supplementation and aged 60 years or older—weak recommendation, very low certainty of evidence These recommendations are intended for inpatients with COVID-19 outside ICU *Equivalent dosages of other steroids may be considered if dexamethasone is not available (although this should be considered as best practice recommendation, taking also into account the indirectness of evidence for steroids other than dexamethasone)
Question 5	Should antiviral agents be administered to inpatients with COVID-19?  Lopinavir/ritonavir should not be administered to hospitalized patients with COVID-19—strong recommendation, moderate certainty of evidence  Pending further results from large RCTs, administration of a 5-day course of remdesivir should be considered in hospitalized patients with COVID-19 pneumonia requiring oxygen supplementation—weak recommendation, very low certainty of evidence  Hydroxychloroquine should not be administered to hospitalized patients with COVID-19—strong recommendation, moderate certainty of evidence  Other antiviral agents should not be administered for treating COVID-19 in hospitalized patients, unless they are administered within RCTs—best practice recommendation (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU
Question 6	Should antibiotics be administered to inpatients with COVID-19?  We recommend against the routine use of antibiotics in hospitalized patients with COVID-19 without proven bacterial infection—strong recommendation, moderate certainty of evidence (for azithromycin); weak recommendation, very low certainty of evidence (for antibiotics in general)  We recommend collection of respiratory specimens for culture or molecular detection of respiratory pathogens, blood cultures, and urinary antigens for Streptococcus pneumoniae and Legionella spp. in hospitalized patients with COVID-19 and suspected bacterial pneumonia—best practice recommendation (based on expert opinion only)  Empirical antibiotic treatment of suspected bacterial pneumonia alongside proper diagnostic procedures, should be considered in patients with COVID-19 with evidence of consolidative radiological lesions—best practice recommendation (based on expert opinion only)  In the case of empirical antibiotic treatment, selection of agents to be administered should follow standard practice for the treatment of bacterial pneumonia—best practice recommendation (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU
Question 7	Should neutralizing monoclonal antibodies and non-steroid immunomodulators be administered to inpatients with COVID-19?  Pending further results from RCTs, we recommend against the administration of neutralizing monoclonal antibodies in hospitalized patients with COVID-19—strong recommendation, moderate certainty of evidence  We recommend considering tocilizumab administration in hospitalized patients with COVID-19 not responding to steroid treatment, with oxygen saturation < 92% on room air (including those already on supplementary oxygen), and with increased inflammatory markers* in the absence of a proven or suspected bacterial or fungal infection**—weak recommendation, very low certainty of evidence  Pending further results from RCTs, baricitinib may be considered in addition to remdesivir in patients requiring high-flow oxygen or non-invasive mechanical ventilation who are not under steroid treatment (e.g., in the presence of contraindications to steroid use)—weak recommendation, low certainty of evidence  Pending further results from large RCTs, we recommend against administration of other non-steroid immunomodulatory agents outside RCTs—weak recommendation, very low certainty of evidence (for anakinra); best practice recommendation for other agents (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU *In the RECOVERY trial, serum C-reactive protein ≥ 75 mg/L **Clinicians should be aware of the following: (i) the 75 mg/L cutoff is based on results of the RECOVERY RCT; (ii) other markers of inflammation may be considered on a case-by-case basis (best practice recommendation); (iii) another best practice recommendation is to avoid tocilizumab administration in patients with severe immunosuppression or in those with other contraindications to tocilizumab administration (low platelet count; risk of gastrointestinal perforation; increase of transaminases > 5 times the upper limit of normal)
Question 8	Should convalescent plasma be administered to inpatients with COVID-19?  Pending further results from RCTs, currently we do not support the administration of convalescent plasma in hospitalized patients with COVID-19 outside RCTs—weak recommendation, low certainty of evidence  Pending further results from RCTs, currently we do not support the administration of anti-COVID-19 hyperimmune immunoglobulin preparations in hospitalized patients with COVID-19 outside RCTs—best practice recommendation (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU
Question 9	Should CPAP/NIV be employed for treating inpatients with COVID-19 with acute hypoxemic respiratory failure?  Unless contraindicated, non-invasive ventilatory support by means of NIV or CPAP is feasible and safe in patients with acute respiratory failure secondary to COVID-19, and should be considered for patients in whom standard oxygen supplementation is not or no longer sufficient and who do not require immediate intubation—best practice recommendation (based on expert opinion only)  CPAP delivery systems allowing for PEEP titration should be preferred, and PEEP should not exceed 10 cmH2O—best practice recommendation (based on expert opinion only) These recommendations are intended for inpatients with COVID-19 outside ICU
Question 10	When can an improved patient with COVID-19 be discharged from an acute care hospital?  Clinically stable patients with COVID-19 who no longer require isolation (or who can be isolated outside the hospital) should be discharged from acute care hospitals when oxygen supplementation is no longer required or with a maximum requirement of low-flow oxygen at 2 L/min through nasal cannula (with the exception of patients already under oxygen supplementation at home at baseline or patients requiring initiation of long-term oxygen therapy after discharge), in line with common practice with other types of non-contagious lower respiratory tract infections, and provided there are no complications or other reasons that require continuation of hospitalization—best practice recommendation (based on expert opinion only)  For patients with COVID-19 still requiring isolation but who could be discharged from a clinical standpoint, isolation outside the hospital (at home, in community facilities, or in long-term facilities, according to the specific need for non-acute care of any given patient) should be supported and made feasible for as many patients as possible—best practice recommendation (based on expert opinion only)

COVID-19 coronavirus disease 2019, CPAP continuous positive airway pressure, NIV non-invasive ventilation, PEEP positive end-expiratory pressure, RCTs randomized controlled trials