SARS Cov2 management

Management

prevention

• hand hygiene, hand washing
• contact precautions & droplet precautions
• recommendations regarding duration of isolation vary & have evolved over tim
  • isolation no longer necessary if asymptomatic, or if masks are used after symptoms improve
  • initially, isolate all those infected, including those with mild disease, until at least 2 weeks after symptoms resolve (WHO)
  • recovered patients should isolate for at least 10 days after symptom onset & for at least 3 days after recovery (early recommendations) [[[A3702|CDC]]]
    • isolation for at least 5 days after symptom onset or, if asymptomatic, after the first positive test (2024) [[[A3702|CDC]]]
  • severely immunocompromised adults with COVID-19 require additional testing & consultation with infectious disease specialists before ending isolation
    • cancer chemotherapy, HIV1 infection with CD4 count < 200/uL. combined immune deficiency or prednisone > 20 mg/day > 14 days
• admission of patient to private room when possible (isolation)
  • after 10 days, retest prior to discontinuing isolation if afebrile for >= 3 days (72 hours)
• face masks for patients & health care providers
  • use of medical face mask when evaluating or transferring symptomatic patient
  • universal masking in hospitals standard practice in Hong Kong, Singapore, other parts of Asia & a handful of U.S. hospitals
  • surgical face masks reduce presence of coronavirus RNA in respiratory droplets & aerosols from infected individuals
    • neither surgical nor cotton face mask worn by infected individual protective from cough at a distance of < 20 cm
  • surgical masks may be adequate protection for aerosol-generating procedures
• maintain distance of at least 2 meters between patients
• proper indoor ventilation with indoor relative humidity of 40-60% associated with fewest COVID-19 cases & deaths
• wearing glasses in the community is not protective

Oxygen

• Oxygen to maintain SaO2 of > 90%
• helmet CPAP curbs a huge inspiratory drive when unchecked, can lead to self-induced lung injury
• no significant difference in outcomes with helmet CPAP vs high-flow oxygen
• CPAP but not high-flow nasal oxygen reduces need for endotracheal intubation relative to standard oxygen therapy
• high-flow oxygen therapy vs conventional oxygen therapy reduces need for mechanical ventilation & decreases time to clinical recovery in patients with severe COVID-19,[221]
• mortality is similar with high-flow oxygen therapy vs Venturi mask
• PaO2 target of 60 mm Hg vs 90 mm Hg results in more days alive without life support in ICU patients with severe hypoxemia
• caution using high-flow nasal oxygen or noninvasive ventilation due to risk of dispersion of aerosolized virus
• clinicians involved in aerosol-generating procedures should wear N95 respirator & eye protection
• dexamethasone 6 mg IV QD reduces mortality by 1/3 in mechanically ventilated COVID-19 patients & by 1/5 in patients requiring oxygen only
  • dexamethasone worsens outcomes in patients not requiring oxygen
• hydrocortisone 200 mg/day not helpful for acute respiratory failure
• prone positioning of benefit in patients requiring oxygen
  • lateral position if prone position not tolerated
  • prone positioning may prevent need for mechanical ventilation
  • self-proning in the emergency department improves oxygen saturation (SaO2 84% to 94% within 5 minutes)
  • duration of proning important & only a subset may respond favorably
  • prone positioning in mildly hypoxemic hospitalized Covid-19 patients requiring oxygen of no benefit possibly because of low adherence
  • prone positioning in awake patients with acute hypoxemic respiratory failure does not reduce endotracheal intubation at 30 days

Treatment overview (literature)

• COVID-19 Treatments overview March 2021

Remdesivir & baricitinib

• Remdesivir may be of marginal benefit (see remdesivir)
  • remdesivir + IFN beta-1a in clinical trial
  • neither remdesivir nor IFN beta-1a benefits mortality (WHO)
• baricitinib + remdesivir superior to remdesivir alone (see ARDS below)
• remdesivir treatment of Covid-19 is not associated with improved survival but is associated with longer hospital stays
• remdesivir without clinical or antiviral benefit in hospitalized patients with Coovid-19
• baricitinib alone in hospitalized patients not on mechanical ventilation may reduce 30 day mortality (see baricitinib)
• Remdesivir may be useful for prevention of hospitalization in a setting capable of IV infusions (i.e. skilled nursing home)
  • 87% reduction in risk for COVID-19-related hospitalization or all-cause death by Day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) in high-risk patients
    • requires 3 IV infusions on consecutive days

Anticoagulation

• prophylactic anticoagulation does not benefit outpatients with Covid-19
• prophylactic-dose LMW heparin for all hospitalized patients with or suspected to have COVID-19
  • prophylactic anticoagulation within 24 hours of hospital admission lowers mortality
  • in-hospital mortality may be higher with therapeutic-dose anticoagulation
• therapeutic anticoagulation improves outcomes & possibly survival in hospitalized but not critically ill COVID-19 patients
• treatment dose anticoagulation for patients on ventilators
• therapeutic anticoagulation with heparin without benefit in critically ill patients & with minimal benefit in noncritically ill patients
• preemptive therapeutic-level heparin no better than prophylactic-dose heparin & possibly unsafe for critically-ill COVID-19 patients
• therapeutic rivaroxaban does not improve outcomes in hospitalized patients
• prophylactic & therapeutic anticoagulation were each associated with ~50% reduction in mortality, vs no anticoagulation.in hospitalized patients
  • no statistical differences between dosing strategies [135=
• therapeutic doses of anticoagulant do not reduce need for organ support
• therapeutic doses of anticoagulant do not improve outcomes in hospitalized patients with elevated D-dimer & are associated with more bleeding than prophylactic anticoagulation
• intermediate-dose anticoagulation (enoxaparin, 1 mg/kg daily) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) does not change outcome
• rivaroxaban 10 mg QD for 30-45 days post hospital discharge suggested
  • prevents some venous thrombombolism in high-risk patients
• nebulized unfractionated heparin may reduce diffuse alveolar damage from pulmonary coagulation, fibrin deposition in microvasculature & hyaline membranes in air sacs
• anticoagulation of outpatients with COVID-19 of no benefit
• antiplatelet agent (P2Y12 inhibitor) of no benefit added to heparin
• antiplatelet agents unlikely to benefit critically ill patients
• apixaban 2.5 mg BID for 30 days after hospitsl discharge of no benefit

ARDS

• For patients with COVID-19 who develop ARDS
  • ARDS marks transition from viral to the inflammatory stage of the COVID-19
  • conservative intravenous fluid strategy
  • empiric treatment for bacterial pneumonia
    • 20% of patients show evidence of early bacterial pneumonia
    • < 50% of patients develop ventilator-associated pneumonia
  • prophylactic LMW heparin unless bleeding or platelet count < 25,000/uL
    • keep platelet count > 50,000/uL, plasma fibrinogen > 200 mg/dL, INR < 1.5
  • consider early mechanical ventilation
    • non invasive ventilation may risk aerosolization & spread of virus
    • delayed mechanical ventilation may be a factor increasing mortality
    • mechanically ventilated patients with severe COVID-19 pneumonia have similar mortality as patients with other causes of severe pneumonia
      • mechanical ventilation duration may be longer for patients with Covid-19
  • lung protective ventilation (permissive hypercapnia)
  • periodic prone positioning during ventilation
    • prone position also suggested to prevent or delay intubation
  • air hunger may occur in ventilated patients
    • consider opioids to reduce anxiety in ventilated patients
  • DNR code status appropriate with mechanical ventilation
  • consideration of extracorporeal membrane oxygenation
  • glucocorticoids may improve outcomes in mechanically ventilated patients
    • dexamethasone 6 mg IV QD reduces mortality by 1/3 & reduces days on a ventilator; meta-analysis finds NNT = 19 to prevent 1 death
    • 12-17 mg dexamethasone no better than 6 mg
    • treatment of ARDS with methylprednisolone may improve outcomes or not
    • methylprednisolone associated with better outcomes than dexamethasone
    • empiric ivermectin reasonable for prevention of Strongyloides dissemination in high-risk patients receiving glucocorticoids
    • NIH does not recommend glucocorticoids for mechanically ventilated patients in the absence of ARDS
    • hydrocortisone 200 mg/day not helpful for acute respiratory failure
    • NIH recommends low-dose glucocorticoids for refractory shock
  • form of non-invasive respiratory support (nasal cannula oxygen, high-flow oxygen, or CPAP) does not affect progression to mechanical ventilation
  • FDA issues emergency use authorization for baricitinib-remdesivir combination to treat hospitalized COVID-19 patients >= 2 years who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation
    • superior to remdesivir alone in reducing recovery time for patients receiving high-flow oxygen or non-invasive ventilation
    • combination associated with fewer serious adverse events than remdesivir alone
    • baricitinib alone associated with an 8.1% reduction in 30-day absolute mortality in patients < 70 years hospitalized with Covid-19 pneumonia, & an 18.5% reduction in 30-day absolute mortality patients >= 70 years (see baricitinib)
    • 13% lower 28-day mortality associated with use of baricitinib alone in patients with severe Covid-19
  • remdesivir alone not recommended in patients who require mechanical ventilation or extracorporeal membrane oxygenation
  • vilobelimab approved for emergency use authorization for patients with severe COVID-19 within 48 hours of starting mechanical ventilation or extracorporeal membrane oxygenation
  • tofacitinib (Xeljanz) reduces respiratory failure & mortality in patients hospitalized with Covid-19 pneumonia
  • baricitinib or another JAK inhibitor lowers mortality 20% in hospitalized Covid-19 patients requiring oxygen when added to dexamethasone
  • thus JAK inhibitors baricitinib & tofacitinib of benefit for Covid-19 pneumonia
  • IL-6 inhibitors & antiplatelet agents (see other therapeutics below)
  • in patients who develop pulmonary fibrosis, lung transplantation may provide the only hope for survival
    • survival 100% for 30 patients after lung transplantation for COVID-19-associated ARDS
  • treatment with convalescent plasma controversial (see below)

other therapeutics

• IL-6 inhibitor data conflicting
  • see IL-6 inhibitors for COVID-19 for tocilizumab, sarilumab, itolizumab
  • among critically ill patients with Covid-19, treatment with IL-6 inhibitor &/or antiplatelet agent with improved 180 day mortality (probabilities 100% & 95%, respectively)
• Anakinra (recombinant IL-1 receptor antagonist)
  • associated with improved survival among COVID-19 patients with ARDS managed with non-invasive ventilation outside of the ICU in a small, retrospective study
  • emergency use authorization for hospitalized patient with pneumonia who require oxygen & at risk for ARDS
    • & likely to have elevated plasma soluble urokinase plasminogen activator receptor
  • not effective for reducing need for mechanical ventilation in patients with severe Covid-19 pneumonia
• mavrilimumab (GM-CSF receptor-alpha antagonist) of benefit for 13 patients not mechanically ventilated with systemic hyperinflammation
• famotidine found to diminish mortality (RR<0.5) in hospitalized patients
  • non-hospitalized patients may also benefit from famotidine
• IL-7 reverses lymphopenia in critically-ill COVID-19 patients without exacerbating inflammation or pulmonary injury
• interferon-beta-1b shortened time to negative nasopharygeal swab SARS CoV-2 RNA (7 vs 12 days) symptom alleviation (4 vs 8 days) & shortened median hospital stay (9 vs 15 days) but did not change outcomes
• nebulized interferon beta-1a may be of benefit
  • of no mortality benefit (WHO)
• peginterferon lambda 180 ug SQ single dose in outpatients within 7 days of symptom onset may facilitate viral clearance
  • reduces hospitalization or an emergency department visit > 6 hours in vaccinated outpatients with Covid-19 (RR=0.49)
• UVC radiation at 222 nm lethal to SARS-CoV-2 thought to be safe for humans
  • for use in indoor areas occupied by people
  • 222 nm UVC does not penetrate skin or eyes
• abatacept (Orencia) & infliximab (Remicade) reduce risk of death in hospitalized patients 37-40%
  • all-cause 28-day mortality
    • 11.0% for abatacept vs 15.1% for placebo
    • 10.1% for infliximab vs 14.5% for placebo
    • 13.8% for cenicriviroc vs 11.9% for placebo
  • neither drug expedites recovery
• abatacept, cenicriviroc, or infliximab did not decrease time to recovery for hospitalized patients with COVID-19 pneumonia
• COVID-19 treatment protocols have been proposed

Early outpatient management of Covid-19

• currently (Oct 2022) no FDA-approved post-exposure prophylaxis for people who may have been exposed to COVID-19
• ursodeoxycholic acid may be of benefit in reducing ACE2 expression in lung (ACE2 is the receptor for SARS Cov2)

oral medications for COVID-19

• see Paxlovid seems to be drug of choice for outpatients
• molnupiravir (Lageviro)
• use of either nirmatrelvir or molnupiravir is associated with reduced hospitalization & mortality in Omicron infected patients
  • RR of hospitalization or death:
    • 0.63 for nirmatrelvir & 0.59 for molnupiravir
  • RR of death: 0.16 for nirmatrelvir & 0.23 for molnupiravir

Monoclonal antibodies to COVID-19

• see monoclonal antibodies to spike glycoprotein
• no longer effective during the Omicron wave

= Convalescent plasma

• Treatment of COVID-19 with convalescent plasma: (see convalescent plasma)

outpatient glucocorticoids

• inhaled budesonide shortens recovery times in outpatients (NNT=8)
  • hospitalizations & deaths not improved
  • inhaled budesonide may be useful for outpatients with asthma or COPD
• intranasal glucocorticoids associated with a lower risk for COVID-19-related hospitalization, ICU admission, or death

outpatient pulse oximetry

• does not reduce hospitalization or mortality
• associated with more healthcare-associated telephone encounters

nasal irrigation

• nasal irrigation twice daily for 14 days after COVID-19 diagnosis reduces hospitalization & death in high-risk outpatients
  • irrigation solution prepared by addition of 2.5 mL 10% povidone-iodine or 2.5 mL (mg?) sodium bicarbonate to 240 mL of isotonic nasal irrigation

Hospital Discharge & Follow-up

• COVID-19 pneumonia discharged on home oxygen have low rates of mortality & low rates of readmission within 30 days
• after patients are afebrile for 14 days, they are considered non-infectious but are not retested
• immunosupressed patients with COVID-19 can shed viable SARS-CoV2 for >=2 months after symptom onset & may need extended quarantine
• best alternative to an office visit during Covid-19 pandemic is telephone visit or videoconferencing

Quarantine

• healthcare workers who test positive are quarantined for 2 weeks & must have 2 negative tests, 24 hours apart before returning to work
• CDC recommends vaccinated & boosted healthcare staff no longer quarantine after high-risk exposures
• CDC has shortened quarantine for close contacts to 10 days without testing if asymptomatic & to 7 days if asymptomatic & negative test < 48 hours prior
• CDC reduced quarantine for asymptomatic Covid-19 positive persons from 10 days to 5 days

Unproven therapies

• Potential therapies with unproven benefit
  • do not use chloroquine or hydroxychloroquine with or without azithromycin : see chloroquine/hydroxychloroquine for COVID-19
  • favipiravir has in vitro activity
  • oseltamivir 75 mg PO every 12 hours of unproven benefit
  • camostat mesylate may inhibit TMPRSS2 which facilitates viral entry into type II pneumocytes
  • no benefit from metformin, ivermectin, or fluvoxamine for Covid-19
    • ivermectin inhibits replication of SARS CoV-2 in vitro
      • 5000-fold reduction in virus at 48h in cell culture after single treatment
      • empiric ivermectin is reasonable for prevention of Strongyloides dissemination in high-risk patients receiving dexamethasone
      • promoted by Front Line COVID-19 Critical Care Alliance
      • NIH treatment guidelines does not recommend for or against use of ivermectin for treatment of COVID-19
      • ivermectin of no benefit for treatment of mild COVID-19
      • WHO & FDA recommend against use of ivermectin for treatment of COVID-19
      • 2 meta-analyses of randomized trials found ivermectin reduced mortality in outpatients (RR=0.38-0.44)
    • fluvoxamine (SSRI & S1R agonist) may reduce risk of clinical deterioration in outpatients with COVID-19
      • not enough evidence to recommend for or against use of fluvoxamine
      • RR of disease progression, hospitization = 0.71
    • fluoxetine may be associated with reduced severity of COVID-19 & reduced risk of mortality (RR=0.72)
  • colchicine promising, but still of uncertain benefit
    • RECOVERY trial stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19
    • not enough evidence to recommend for or against use of colchicine in outpatients
      • colchicine not recommended in hospitalized patients
    • colchicine does not reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia
  • vitamin D has been suggested, but data is inconsistent
    • component of COVID-19 cocktails
    • low levels of serum 25-OH vitamin D may be associated with increased risk
    • vitamin D3 of no benefit for hospitalized patients with COVID-19
    • vitamin D may reduce Covid-19 ICU admission/mortality (RR=0.41) when administered after diagnosis (dose, duration, & mode of administration unknown)
    • vitamin D supplements do not reduce risk of Covid-19
  • zinc supplement 25 mg PO BID may be beneficial, especially in hospitalized patients
  • melatonin may be useful
  • icosapent ethyl may reduce inflammation & improve symptoms in COVID-19 patients
  • aspirin 81 mg QD prior to or upon hospitalization may lower risk of ICU admission & mechanical ventilation (observational cohort study, 412 patients)

Therapies of no benefit

• high-dose zinc &/or ascorbic acid
• combination of antivirals lopinavir & ritonavir of no benefit [62, 161]
• proton pump inhibitors associated with risk of severe or fatal COVID-19 (RR=1.46-1.67)
• azithromycin of no benefit
• JAK2/IRAK1 inhibitor pacritinib no better than placebo in patients with severe Covid-19

Investigational treatment

• also see investigational treatment of COVID-19

Medications, Comordities & COVID-19

• AHA/ACC/HFSA recommend patients continue taking ACE inhibitors, ARBs
  • statement seemed to arise (no data found) after suggestion that ACE inhibitors & ARBs could increase risk of ARDS
  • in hospitalized COVID-19 patients with hypertension, inpatient use of ACE inhibitor/ARB associated with lower risk of all-cause mortality
    • not associated with severity & outcomes of COVID-19 infection
  • ACE inhibitor/ARB with beneficial effect on patients with hypertension
  • in critically ill patients, initiation of an ACE inhibitor or an ARB did not improve, but likely worsened, clinical outcomes
• statins appear to reduce risk of severe or fatal COVID-19 (30%)
  • continued use of statin associated with lower mortality than discontinued use (RR=0.65); for comparison no statin use RR=0.72
  • risk for mechanical ventilation also lower with continued use of statin (RR=0.70)
• FDA denies evidence linking NSAIDS with worsening of COVID-19 symptoms
• disease-modifying therapy for multiple sclerosis is not a risk factor
• metformin lowers mortality in patients with type-2 diabetes (RR=0.33)

Conservation with limited resources

• FDA recommends healthcare providers consider reusing gloves if supply is compromised
• FDA suggests ventilators labeled for the home may be used for hospitalized patients

Surgery

• risk for postoperative complications remains elevated for 8 weeks after Covid-19
  • postpone elective surgery for at least 8 months

Prognosis

• mortality among critically ill patients with COVID-19 is 67%
• myocardial ischemia determined by high sensitivity serum troponin is a substantial risk factor for invasive & non-invasive ventilation & mortality (RR=5-10)

Institutional prevention

• quanrantine of new arrivals for 2 weeks
• social distancing
• mandated face masks

Public prevention

• hand washing
  • alcohol-based hand sanitizers kill COVID-19
• social distancing: maintain distance of 6 feet
• transmission of COVID-19 lower with social distancing of 3.3 feet
  • avoid large social gatherings
• CDC recommends all persons should wear face masks in public
  • face mask use results in large risk reduction N95 mask best
• persons wearing eyeglasses may be at lower risk for COVID-19
• stay-at-home orders associated with a reduction in projected COVID-19 hospitalizations in 4 of 4 states - Colorado, Minnesota, Ohio, Virginia
• if U.S. had enacted social distancing & other control measures 1 week earlier, it could have averted 36,000 or 55% of reported deaths as of May 3
• prevention measures work in the absence of effective treatments or vaccines
• school closures associated with fewer cases & diminished mortality
  • ~13 fewer deaths per 100,000 population within 27-42 weeks
• BCG vaccination does not affect SARS-CoV-2 infection rates but may reduce COVID-19 deaths
• NIH does not recommend any drug for pre- or post-exposure prophylaxis
• some evidence suggests that povidone-iodine & hydrogen peroxide oral rinses may reduce viral load & transmission of SARS CoV-2
• 15 seconds of >=0.5% povidone-iodine nasal antiseptic solution inactivates SARS-CoV-2 & may reduce burden of SARS CoV2 delivered to lungs
  • *povidone-iodine labeled for topical use may be toxic as oral rinse or intranasal antiseptic*
  • povidone-iodine mouthwash 5 & 10 mg/mL (RxNorm)
• COVID-19 vaccines under development (also see COVID-19 vaccine)
  • insertion of the spike glycoprotein into an adenovirus vector
  • mRNA vaccine shows promise in small clinical trial of 45 individuals
• germicical UV radiation may be useful in decontaminating aerosolized SARS CoV-2 in indoor settings
• see COVID-19 patient information

Pandemic management

• see pandemic

Notes

• Infectious Disease Society of America guidelines on the Treatment and Management of Patients with COVID-19

Additional terms

• investigational treatment of COVID-19
• monoclonal antibody to spike glycoprotein of SARS-CoV2 (COVID-19)
• severe acute respiratory syndrome coronavirus 2; SARS-CoV2; Wuhan coronavirus

Patient information

SARS CoV2 management patient information