Mahatma Gandhi Institute of Medical Sciences Kasturba Hospital Sevagram

Protocol COVID-19: Management in hospitalized adults

Objective To evaluate for features associated with severe illness and identify organ dysfunction or other comorbidities that could complicate potential therapy. Determine severity and prognosis of patients admitted with COVID-19. The severity of COVID-19 is categorized into mild (symptoms but no dyspnoea or abnormal imaging), moderate (lower respiratory disease w/ SpO2 >94% on room air), severe (SpO2 ≤ 94% on room air), or critical (ICU).

Initially, check the following laboratory studies:

●Complete blood count (CBC) with neutrophil-lymphocyte ratio ●Glucose, Creatinine, Na, K ●C-reactive protein (CRP) ●Ferritin ●D-dimer

Check the following studies at baseline and repeat them if abnormal or with clinical worsening:

●Lactate dehydrogenase (LDH) repeated alternate days if elevated ●Troponin, repeated every two to three days if elevated ●Electrocardiogram (ECG)  Portable chest radiograph  Reserve chest CT for circumstances that might change clinical management  Two sets of blood cultures if clinical suspicion of sepsis

Procalcitonin is not recommended for most patients admitted with COVID-19. Routine empiric antibiotics are not recommended. • Use only if concerned for bacterial co-infection. Procalcitonin not reliable in cytokine storm

Prevention of and evaluation for venous thromboembolism Enoxaparin prophylaxis of venous thromboembolism for all hospitalized moderately or severely ill patients with COVID-19

COVID-19-SPECIFIC THERAPY

Dexamethasone— For severely ill patients with COVID-19 who are on supplemental oxygen or ventilatory support at a dose of 6 mg daily for 10 days or until discharge, whichever is shorter. 6 mg IV or PO daily × 10 days.

Dexamethasone (or other glucocorticoids) not be used for either prevention or treatment of mild to moderate COVID-19 (patients not on oxygen)

Remdesivir — for hospitalized patients with those requiring low-flow supplemental oxygen. Not for patients with no hypoxia or those on mechanical ventilation will not meet the criteria because it has not been proven whether remdesivir confers clinical benefit in these group of patients.

Dose: 200 mg IV load, then 100 mg IV q24h for five days.

Remdesivir should not be initiated or should be stopped if ALT is ≥5x ULN. For patients with eGFR < 30 ml/min, remdesivir may be considered on an individual basis considering risk/benefit.

Do not use the following drugs for any inpatient, regardless of the severity of the disease:

 Hydroxychloroquine/chloroquine  Favipiravir  Azithromycin (with or without hydroxychloroquine)  Ivermectin  Lopinavir-ritonavir  Zinc  Vitamin D  Convalescent plasma  IL-6 pathway inhibitors (Tocilizumab)  Interferons

Determine severity and prognosis of patients admitted with COVID-19. The severity of COVID-19 is categorized into: 1. Mild (symptoms but no dyspnoea or abnormal imaging), 2. Moderate (lower respiratory disease w/ SpO2 >94% on room air), 3. Severe (SpO2 ≤ 94% on room air), or critical (ICU).

Nonsevere disease — For most hospitalized patients with nonsevere disease, supportive care only, with close monitoring for clinical worsening.

Severe (including critical) disease — Prioritize COVID-19-specific therapy for hospitalized patients who have severe disease. The approach depends on the oxygen or ventilatory requirement:

1. Patients with severe disease (ie, with hypoxia) but without oxygen requirement – For these patients, use remdesivir if patient meets EUA criteria. Prioritize remdesivir for patients on low-flow oxygen supplementation at baseline. Do not use dexamethasone in such patients. 2. Patients with severe disease who are receiving supplemental oxygen – For patients on supplemental oxygen (including those who are on high-flow oxygen and noninvasive ventilation), use low-dose dexamethasone. 3. Patients with severe disease who require mechanical ventilation – For such patients, low-dose dexamethasone as RECOVERY trial data suggest that dexamethasone improves mortality in this population

CYTOKINE STORM SYNDROME

Suspect if:

Escalating O2, shock, myocardial dysfunction • CRP > 50 mg/L and at least two of… Ferritin > 500 ng/mL; LDH > 300 U/L; D-dimer > 1000 ng/mL (r/o VTE)

• Other markers: neutrophilia, lymphopenia, elevated LFT and ESR, DIC markers (TCP, falling fibrinogen, prolonged PT/PTT). sIL2R (sCD25), IL-6

SEPSIS

• Norepinephrine for goal MAP > 65 • Conservative fluid management: use 250 – 500 cc boluses with dynamic measures of responsiveness