Methylprednisolone

Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients

survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated

Early use of a combined anti-inflammatory (corticosteroids and Enoxaparin) and antiviral drugs treatment in patients with moderate to severe COVID-19 pneumonia prevent complications of the disease and improve clinical outcomes

Early low-dose prolonged treatment was associated with significantly lower risk of death and decreased dependence on mechanical ventilation. Improvements in systemic inflammation and oxygenation were observed, as well. Sample size: 83 + 90 control. Dosage: 80 mg IV loading dose; 80 mg daily in a continuous infusion until clinical improvement (for at least 8 days); 16 mg orally or 20 mg IV twice daily until further improvement in inflammation and oxygenation. Endpoint: Need for ICU referral, intubation, or death within 28 days composite (primary).

Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in patients with COVID-19 pneumonia

use of methylprednisolone in a dose of 30 mg twice daily was associated with rapid improvement in oxygenation and decline in CRP levels

A case report of clinical improvement and improvement of radiological findings in a critically ill patient after short-duration moderate-dose corticosteroid treatment. Dosage 80 mg twice a day for 3 days, then 40 mg twice a day for the following 3 days.

In vitro manifests ACE2 agonist activity and decreases IL-6 secretion in M1 macrophages. Theoretical amelioration of ACE2 depletion by virus attachment.

Medium to small methylprednisolone doses might decrease inflammation in patients in severe to critical conditions. Sample size 9 patients. Dosage 40 mg/d if body weight ≤ 80 kg for the first 3-4 days, and then 20 mg/d for the next 3 days or more with a total of less than 8 days. If body weight is over 80 kg, 80 mg/d for 3-4 days and 40 mg/d for the next 3 days or more with a total of less than 8 days. Endpoints - IL-6 levels; lymphocyte count; CRP; CT findings.

Patients in the early phase of excessive inflammation could benefit from short-term low to moderate corticosteroid treatment if their lactate dehydrogenase levels are less then two times the upper limit of normal. Sample size: 311+187 validation cohort. Dosage: 40–80u2005mg/d (0.75–1.5u2005mg/kg/d) of methylprednisolone for 3 days, then was tapered to 20u2005mg/d, with a total treatment period of less than 7 days. Endpoints: Requirement of invasive mechanical ventilation; adverse effects.

Early methylprednisolone treatment (optionally in combination with tocilizumab) may improve clinical outcomes in non-intubated COVID-19 patients. Sample size: 45 + 56 with tocilizumab + 66 control. Dosage: 1 mg/kg for 5 days (+ optionally tocilizumab 8mg/kg intravenously or 162mg subcutaneously). Endpoint: Intubation/death-free survival.

Rapid and significant clinical improvement in pacients who failed to respond to azithromycin, hydroxychloroquine and two doses of tocilizumab treatment. Sample size: 5. Dosage: 1.5 mg/kg. 

beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, non-invasive ventilation or death

Early treatment (in combination with favipiravir) in severe COVID-19 may prevent disease progression. Sample size: 11. Dosage: 80 (initial), 250, or 500 mg/day for 3–6 days.

Severe COVID-19 patients treated with methylprednisolone pulse at the onset of the pulmonary phase of the disease showed shorter time to clinical improvement and lower mortality rate compared to the control group. Sample size: 34 + 28 control. Dosage: IV 250u2005mg/day for 3u2005days.

Early methylprednisolone low to medium dosage treatment of severe COVID-19 patients younger than 65 years old significantly reduced progression to critical severity and mortality. No statistically significant differences were observed in older patients. Sample size: 175. Dosage: 50u201080 mg daily.

COVID-19 patients with high inflammation and compromised respiratory functions (unlike those without respiratory compromise) significantly benefited from week-2 pulse methylprednisolone treatment when compared to non-week-2 scheme of methylprednisolone treatment or no methylprednisolone administration at all. Sample size: 61 (week-2 methylprednisolone) + 33 (other than week-2 methylprednisolone) + 148 (no methylprednisolone). Dosage: 125-250 mg daily for 3 days during the second week of COVID-19. Endpoints: Time to death and time to death or endotracheal intubation.

Patients with critical (but not those with less severe) COVID-19 benefited (60-day mortality) from short-therm low-dose (but not high dose) treatment with methylprednisolone. Sample size: 174 + 164 control. Dosage: No more than 80 mg daily for no more than 7 days.

Marked improvement in supplementary oxygen requirement, temperature, and CRP. Equally effective as dexamethasone in moderate to severe COVID-19.
Sample size: 65 (methylprednisolone) + 35 (dexamethasone). Dosage: 0.5 mg/kg twice daily for 5 days.

In combination with anakinra. The treatment group patients with COVID-19-linked hyperinflammation were in a significantly lower adjusted and unadjusted risk of death compared to a historical control. Sample size: 65 + 55 control. Dosage: 1 mg/kg loading dose; 0.5 mg/kg twice daily on days 1-5; 0.25 mg/kg twice daily on days 6-10; 0.25 mg/kg daily (optionally divided into two doses) on days 11-14. Endpoint: 28-day mortality.

Patients with severe COVID-19 pneumonia not intubated at the baseline were in a significantly lower risk of mechanical ventilation and mechanical ventilation or death composite when treated with methylprednisolone compared to the control. These patients had in average more ventilator- and ICU-free days. 28-day mortality was not significantly different between the groups, however. Sample size: 153 + 294 control. Dosage: 1.78 mg/kg (median) full dose for 5 days (median), for 10 days total, including deescalation (median). Endpoint: Death or mechanical ventilation by the day 28 (primary).

In combination with IVIg. Statistically significant improvement in oxygenation, lower rate of progression to mechanical ventilation, and reduced length of hospital stay in patients with alveolar-arterial gradient greater than 200 mm Hg (none of the subjects with lower gradient progressed to mechanical ventilation). Sample size: 16 + 17 control. Dosage: 40 mg daily for 3 days (30 minutes before IVIg infusion).

In combination with IVIg. Low-dose corticosteroid treatment at the early stage of severe COVID-19 significantly reversed deterioration of clinical status (including respiratory and oxygenation indicators, pulmonary imaging outcomes, markers of inflammation, and other biochemical indicators) and decreased mortality. Sample size: 239 (40 of which were severe). Dosage: 40-80 mg daily for 7-14 days; in more severe cases the initial pulse of up to 160 mg with gradual deescalation upon stabilisation.

Patients with respiratory failure in the late phase of COVID-19 in a small case series might have benefitted from methylprednisolone pulse. Sample size: 4. Dosage: 1000 mg daily for three days.

Used with or withour anakinra. Glucocorticoid therapy in severe non-ICU COVID-19 patients was associated with numerical (but not statistical) decrease in death rate. Sample size: 70 (methylprednisolone) + 35 (methylprednisolone + anakinra) + 3 (methylprednisolone + tocilizumab) + 63 control. Dosage: 120 mg daily on days 1-3; 40 mg prednisone equivalent on days 4-10; 20 mg prednisone equivalent on days 11-17; 10 mg prednisone equivalent on days 18-24 .

Methylprednisolone use was associated with faster virus negative conversion. Its efficacy was improved if administered no more than 3 days after hospital admission. The length of hospital stay was shorter in patients (having the same daily dose) who received a sub-400 mg cumulative dose. Methylprednisolone in the total cumulative dose of sub-400 mg had only minor effect on physiological and biochemical indexes in severe patients, however. Sample size: 46 (severe to critical) + 10 (mild to moderate) + 3 control (severe to critical) + 15 control (mild to moderate). Dosage: IV injection once or twice a day. Total cumulative dose of 0.75 to 1.5 mg/kg.

Lower mortality and higher odds of renal and pulmonary function improvement in African American patients with ARDS and acute kidney injury (AKI) compared to control. In patients of the lower methylprednisolone dosing subgroup an improvement in renal functions was more frequent compared to the higher dosing subgroup. The same was noted for pulmonary functions. Sample size: 37 + 38 control. Dosage: 1 mg/kg daily (early AKI/ARDS group) or 2 mg/kg daily (late AKI/ARDS group) in two divided IV doses for 3 days, then oral administration (or IV, if oral not possible) over 2 weeks. Endpoint: Survival by day 21 (primary).

In combination with tocilizumab. The treatment was associated with a significant decrease in markers of inflammation and an increase in lymphocyte counts in critical COVID-19 patients. The observed ratio of severely or critically ill patients who were discharged from hospital (72%) and overall mortality (20%) were considered by the authors to be indicative of the treatment's efficacy.

The planned sample size was not achieved, which might be the reason why an intention-to-treat analysis did not find a significant difference in the primary outcome between the treatment and the control groups. However, per protocol analysis found a significant benefit for the treatment group. Sample size: 35 + 29 control. Dosage: 40 mg twice a day on days 1-3; 20 mg twice a day on days 4-6. Endpoint: Death, ICU admission, or noninvasive ventilation requirement composite (primary).

Methylprednisolone promoted SARS-CoV-2 RNA replication in human macrophages in vitro and in golden Syrian hamsters' respiratory tracts; however, when used in a hamster model in combination with remdesivir, SARS-CoV-2-related weight loss was prevented and viral loads were decreased. Methylprednisolone alone seemed to dampen inflamation. Attenuated antibody response observed in methylprednisolone monotherapy was not present in this combinational treatment.

Corticosteroid treatment was associated with a better overall outcome. Primary endpoind: Need for mechanical ventilation or death.

Alone or combined with tocilizumab. Reduced in-hospital mortality in COVID-19 pneumonia patients. Dosage: 250 mg daily for 3 days (or 120 mg daily if lopinavir/ritonavir was also administered).

Treated ARDS patients mechanically ventilated at the baseline had statistically significantly more ventilator-free days and shorter length of hospital stay compared to control. There was no significant difference in mortality and more positive blood cultures were detected among patients in the treatment group, however. Sample size: 32 + 45 control. Dosage: 1 mg/kg daily (median) for 5 days (median). Primary outcome: Ventilator-free days within first 28 days.

A statistically significantly better clinical status, shortened length of hospital stay, and lower need for mechanical ventilation was observed in methylprednisolone-treated patients compared to the dexamethasone-treated ones. Sample size: 44 + 42 dexamethasone control. Dosage: 2 mg/kg/day. Primary outcomes: 28-day mortality and the clinical status on an ordinal scale.

A generally good clinical outcome was observed in pregnant patients with COVID-19 treated using anakinra and methylprednisolone. Sample size: 14. Dosage: 80 mg (median) a day for a median duration of 10 days. 

A patient diagnosed with multisystem inflammatory syndrome related to COVID-19 was successfully treated using high-dose methylprednisolone, anakinra, acetylsalicylic acid, and IVIg. Sample size: 1. Dosage: 250 mg every 6 hours. 

A paediatric patient diagnosed with COVID-19-related multisystem inflammatory syndrome was successfully treated using methylprednisolone, anakinra, and IVIg. Sample size: 1. Dosage: 2–10 mg/kg daily, based on clinical status. 

A paediatric patient with severe COVID-19, requiring extracorporeal membrane oxygenation, was successfully treated using methylprednisolone, anakinra, and remdesivir. Sample size: 1. Dosage: 40 mg twice a day for 3 days. 

The results suggest that early methylprednisolone treatment initiation can improve outcomes of COVID-19 paediatric patients with multisystem inflammatory syndrome. The analysed treatment protocol includes dosage change and anakinra or IVIg administration upon clinical worsening. Sample size: 31. Dosage: 2–10 mg/kg. 

A paediatric patient on ECMO was treated with remdesivir, methylprednisolone, IVIg, and anakinra. Sample size: 1.