Corticosteroid prevents COVID-19 progression within its therapeutic window: a multicentre, proof-of-concept, observational study

Abstract

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6-44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.

Beneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection

“…In the Brazilian trials, dexamethasone and methylprednisolone was injected intravenously for five days [20,21]. The treatment period of oral methylprednisolone for the Chinese patients was less than seven days [22]. In our study, the tissue viral loads in hamsters treated with a single intramuscular dose of methylprednisolone increased at 4 dpi and remained detecteble at 14…”

“…Similar beneficial effect of dexamethasone or methylprednisolone has also been observed in Brazilian patients hospitalized with COVID-19 who were either suffering from moderate to severe acute respiratory distress syndrome [20] or at the age of more than 60 years-old [21]. Consistent with this trend, among Chinese COVID-19 patients with marked radiological progression, use of glucocorticoids for a short term and at low to moderate dose reduced the need for invasive mechanical ventilation only in a group at an early phase of excessive inflammation with a lactose dehydrogenase level of less than two times the upper limit of normal [22]. Since COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 [1,23], both reduction of viral loads and alleviation of inflammation are desired in its treatment.…”

“…In two other Brazilian studies, only hospitalized patients who were either suffering from moderate to severe acute respiratory distress syndrome or over 60 years of age had survival benefits after treatment with dexamethasone or methylprednisolone [20,21]. Likewise, beneficial effects of corticosteroid were only seen in a subset of Chinese patients at the early phase of excessive inflammation [22]. It is not known whether inflammation is insignificant or non-responsive to glucocorticoid in patients with less severe COVID-19.…”

“…Golden Syrian hamsters infected with SARS-CoV-2 represent a good small animal model in which symptoms and pathological changes similar to those of mild to moderate COVID-19 in humans can be seen [29,35]. The beneficial effect of dexamethasone and methylprednisolone was observable only in certain groups of COVID-19 patients but not universally [19][20][21][22]. This and the potential risk of glucocorticoids in sensitizing human cells to SARS-CoV-2 and boosting viral RNA replication ( Figure 1) prompted us to examine the effect of methylprednisolone in SARS-CoV-2-infected hamsters more systematically.…”

Preventive home therapy for symptomatic patients affected by COVID-19 and followed by teleconsultations

“…The latter could explain the microvascular damage leading to disseminated intravascular coagulation (manifested as thrombosis, thrombocytopenia, and gangrene of extremities), anti-phospholipid syndrome, and mimicry of vasculitis. On the basis of these considerations we have proposed telemedicine [ 10-12 ] as treatment of COVID-19 patients ( Table 1 ), the association of low molecular weight heparin (LMWE) (4000 uI or 6000 each day on the basis of weight and corticosteroid (prednisone 25 mg in the morning and 12,5 in the evening: dosage not immunodepressive but with antiinflammatory activity) to reduce the cytokine storm) [ 13 , 14 ]. Usually, we add azithromycin for its anti-inflammatory properties [ 15 ], one tablet daily for six days.…”