Prophylaxis for COVID-19
It should be noted that there is no cure or Magic-bullet for the prevention or treatment of COVID-19. While there is extremely limited data, the following “cocktail” may have a role in the prevention/ mitigation of COVID-19 disease. This cocktail is inexpensive, safe, and widely available. It should be noted that recent evidence suggests that Vitamin D deficiency increases the risk of symptomatic COVID19 and from dying from the disease.[1,2] Vitamin D supplementation may therefore be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations; i.e. the elderly, those of color, obese and those living > 45o latitude.
• Vitamin D3 1000-3000 iu/day. Note RDA (Recommended Daily Allowance) is 800-1000 iu/day. The safe upper-dose daily limit is likely < 4000 iu/day. [1-16]
• Vitamin C 500 mg BID (twice daily) and Quercetin 250 mg daily [17-28] Note that prolonged high dose quercetin has very rarely been associated with hypothyroidism. [29,30] Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored.
• Melatonin (slow release): Begin with 0.3mg and increase as tolerated to 2 mg at night. [31-38] • Zinc 30-50 mg/day (elemental zinc). [17,24,26,27,39-43]
• Famotidine 20-40 mg/day [44-48]
• B complex vitamins [49-53]
• Optional/Experimental: Interferon-α nasal spray for health care workers [54]
• Optional: Ivermectin for postexposure prophylaxis (see ClinTrials.gov NCT04422561)
Symptomatic patients at home (for the duration of acute symptoms)
• Vitamin C 500 mg BID and Quercetin 250-500 mg BID
• Zinc 75-100 mg/day (elemental zinc)
• Melatonin 10 mg at night (the optimal dose is unknown) [38]
• Vitamin D3 2000-4000 iu/day
• ASA 81 -325 mg/day (unless contraindicated). ASA has antiinflammatory, antithrombotic, and antiviral effects.[55,56] Platelet activation may play a major role in propagating the prothrombotic state associated with COVID-19. [57]
• Famotidine 40 mg BID (reduce dose in patients with renal dysfunction) [44-47]
• B complex vitamins
• Optional (highly recommended): Ivermectin 150-200 ug/kg orally (repeat on day 2). Alternative strategy is a dose of 12 mg within 24 hours of symptom onset and then repeated 24 hours later. [58-65]
• Optional: Vascepa (Ethyl eicosapentaenoic acid) 4g daily or Lovaza (EPA/DHA) 4g daily; alternative DHA/EPA 4g daily. Vascepa and Lovaza tablets must be swallowed and cannot be crushed, dissolved or chewed. Omega-3 fatty acids have anti-inflammatory properties and play an important role in the resolution of inflammation. In addition, omega-3 fatty acids may have antiviral properties. [26,66-69]
• Optional: Interferon-α/β s/c, nasal spray or inhalation. [54,70-72] It should be noted that Zinc potentiates the effects of interferon.[73,74]
• In symptomatic patients, monitoring with home pulse oximetry is recommended (due to asymptomatic hypoxia). The limitations of home pulse oximeters should be recognized, and validated devices are preferred.[75] Multiple readings should be taken over the course of the day, and a downward trend should be regarded as ominous.[75] Baseline or ambulatory desaturation < 94% should prompt hospital admission. [76] The following guidance is suggested: [75] Page 6 of 34 | EVMS Critical Care COVID-19 Management Protocol 10-22-2020 | evms.edu/covidcare
o Use the index or middle finger; avoid the toes or ear lobe
o Only accept values associated with a strong pulse signal
o Observe readings for 30-60 seconds to identify the most common value
o Remove nail polish from the finger on which measurements are made
o Warm cold extremities prior to measurement
• Not recommended: Hydroxychloroquine (HCQ). The use of HCQ is extremely controversial.[77] The best scientific evidence to date suggests that HCQ has no proven benefit for post exposure prophylaxis, for the early symptomatic phase and in hospitalized patients. [78-92] Considering the unique pharmacokinetics of HCQ, it is unlikely that HCQ would be of benefit in patients with COVID-19 infection (it takes 5-10 days to achieve adequate plasma and lung concentrations).[87,93-95] Finally, it should be recognized that those studies which are widely promoted to support the use of HCQ are severly methodologically flawed.[96-99]
• Not recommended: Systemic or inhaled corticosteroids (budesonide). In the early symptomatic (viral replicative phase), corticosteroids may increase viral replication and disease severity.[100] An OpenSAFELY analysis in patients with COVID-19 demonstrated a higher risk of death in COPD and asthmatic patients using high dose ICS. [101] The role of ICS in the pulmonary phase is unclear as patients require systemic corticosteroids to dampen the cytokine storm, with ICS having little systemic effects.
Mildly Symptomatic patients (on floor/ward in hospital):
• Vitamin C 500-1000 mg q 6 hourly and Quercetin 250-500 mg BID (if available)
• Zinc 75-100 mg/day
• Melatonin 10 mg at night (the optimal dose is unknown) [38]
• Vitamin D3 20 000 – 60 000 iu single oral dose. Calcifediol 200 -500 μg is an alternative. [102] This should be followed by 20 000 iu D3 (or 200 μg calcifediol) weekly until discharged from hospital. Calcifediol is more efficiently absorbed, achieves 25-OH vitamin D levels quicker and is three times more potent than vitamin D3. [103,104] However, it is important to note that the optimal dose of vitamin D in the acute setting is unknown.[105,106] Very high doses may paradoxically block the vitamin D receptor.
• B complex vitamins
• Enoxaparin 60 mg daily [62,107-120] Consider increasing the dose to 1mg/kg q 12 hourly in those with a high D-Dimer or an increasing D-Dimer (see Xa monitoring below).
• Methylprednisolone 40 mg q 12 hourly; increase to 80 mg and then 125mg q 12 hourly in patients with progressive symptoms and increasing CRP. There is now overwhelming and irrefutable evidence that corticosteroids reduce the risk of death in patients with the pulmonary phase of COVID-19 i.e those requiring supplemental oxygen or higher levels of support. [121- 133] The role of inhaled corticosteroids (budesonide) is unclear and appears to be rather limited.
Istead of Methylprednisolone you may use DEXAMETHASONE .
• Famotidine 40 mg BID (20 -40 mg/day in renal impairment). [44-48]
• Optional (highly recommended): Ivermectin 150-200 ug/kg orally (repeat on day 2). Alternative strategy is a dose of 12 mg within 24 hours of admission and then repeated 24 hours later. [58- 65]
• Optional: Vascepa (Ethyl eicosapentaenoic acid) 4g daily or Lovaza (EPA/DHA) 4g daily; alternative DHA/EPA 4g daily.
• Optional (not recommended): Remdesivir, 200 mg IV loading dose D1, followed by 100mg day IV for 9 days. [134,135] This agent has been reported to reduce time to recovery (based on an ordinal scale) in patients requiring low levels of supplemental oxygen. [135,136] The recently published SOLIDARITY trial demonstrated no mortality benefit of this agent in the entire Page 7 of 34 | EVMS Critical Care COVID-19 Management Protocol 10-22-2020 | evms.edu/covidcare treatment cohort or any subgroup.[137] Considering the high cost of this agent and the lack of benefit on patient centered outcomes the role of this drug seems very limited.
• N/C 2L /min if required (max 4 L/min; consider early t/f to ICU for escalation of care).
• Avoid Nebulization and Respiratory treatments. Use “Spinhaler” or MDI and spacer if required.
• T/f EARLY to the ICU for increasing respiratory signs/symptoms, increasing oxygen requirements and arterial desaturation
