Infectious Diseases I
ii.
Fluid resuscitation: Conservative management strategy using balanced crystalloid solutions
iii.
Vasopressors: Norepinephrine as first line; vasopressin or epinephrine as second line
iv.
Inotropes: Dobutamine if cardiac dysfunction or persistent hypoperfusion despite fluid resusci-
tation and norepinephrine
Corticosteroids: See Immunomodulation section in the text that follows.
vi.
Empiric antibiotic therapy should be reserved for patients with confirmed of high suspicion of
concomitant bacterial infection.
Anticoagulation without contraindication or other compelling indication for therapeutic
anticoagulation
Hospitalized patients not requiring oxygen should receive prophylactic heparin
ii.
In non-ICU and non-pregnant hospitalized patients requiring conventional oxygen therapy
AND with a d-Dimer above the upper limit of normal should receive therapeutic heparin for 14
days or until they are transferred to the ICU or discharged from the hospital, whichever comes
first. Pregnant patients should receive prophylactic heparin as appropriate.
iii.
Hospitalized patients requiring high-flow oxygen, noninvasive or invasive mechanical ventila-
tion, or ECMO should receive prophylactic heparin.
| d. | Immunomodulation |
|---|
Corticosteroids
| (a) | Dexamethasone (or equivalent-dose prednisone, methylprednisolone, or hydrocortisone) |
|---|
6 mg per day orally or intravenously for up to 10 days or until hospital discharge is
recommended for COVID-19 treatment in hospitalized patients requiring increased
amounts of supplemental oxygen or MV or ECMO.
| (1) | The largest corticosteroid study to date is the RECOVERY trial, a randomized, open- |
|---|
label trial comparing dexamethasone 6 mg orally or intravenously once daily for up
to 10 days with usual care alone in 6425 patients (dexamethasone 2104; usual care
4321) hospitalized with COVID-19. At baseline, 3883 patients required supplemental
oxygen, and 1007 required MV.
| (A) | Dexamethasone decreased 28-day mortality (primary outcome) (dexamethasone |
|---|
22.9% vs. usual care 25.7%; age-adjusted rate ratio 0.83; 95% CI, 0.75–0.93;
p<0.001).
| (B) | Results were similar among patients who required MV (29.3% vs. 41.4%; rate |
|---|
ratio 0.64; 95% CI, 0.51–0.81) and those receiving supplemental oxygen (23.3%
vs. 26.2%; rate ratio 0.82; 95% CI, 0.72–0.94). There was no difference among
patients not requiring respiratory support.
| (b) | The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group |
|---|
conducted a meta-analysis of seven controlled trials encompassing 1703 critically ill
patients (requiring supplemental oxygen or MV) with COVID-19, including 1007 patients
(15.7% of end enrollment) enrolled early in RECOVERY, showed that corticosteroids were
associated with lower 28-day all-cause mortality compared with placebo or usual care (OR
0.66 [95% CI, 0.53–0.82]; p<0.001).
| (c) | The prospective, randomized, controlled COVID STEROID 2 trial evaluated dexamethasone |
|---|
6 mg or 12 mg daily for up to 10 days in 982 hospitalized patients.
| (1) | Median number of days alive without life support at 28 days was 20.5 days (interquartile |
|---|
range [IQR] 4.0–28.0) vs. 22.0 days (IQR 6.0–28.0) (adjusted mean difference 1.3 days
(95% CI, 0–2.6; p=0.07).
| (2) | No difference was found in 28-day or 90-day mortality. |
|---|
ii.
Other immunomodulators
| (a) | Toclizumab: Anti-IL-6 receptor monoclonal antibody (alternative class agent: sarilumab) |
|---|