In a recent study published by the New England Journal of Medicine, investigators  studied the compassionate use of remdesivir to treat patients with severe COVID-19 complications. Participants consisted of patients who had tested positive for the virus and had oxygen saturation levels of 94 or less while they were breathing ambient air or were on oxygen support. Patients received a 10-day trial of the drug, in which 200mg were administered intravenously on the first day and 100mg were administered daily for the remaining nine days. The investigators concluded that remdesivir led to clinical improvement in 36/53 patients.


Compassionate use of Remdesivir to Treat Patients with Severe COVID-19

A study published in the Journal of Allergy and Clinical Immunology aimed to assess the efficacy and safety of using ruxolitinib, a Janus-associated kinase inhibitor, in treating patients with severe COVID-19.  Patients aged 18 years and up diagnosed with severe COVID-19 based on Chinese management guidelines were recruited for this study.  The study participants were randomly placed into two groups: a group treated with ruxolitinib and standard COVID-19 care and a group with a placebo treatment of vitamin C and standard care.  It was determined that although ruxolitinib treatment did not result in significantly quicker clinical improvement, the ruxolitinib recipients exhibited a numerically accelerated clinical improvement, meaning that more patients who received ruxolitinib demonstrated a quicker recovery from lymphopenia and tomography improvement than the number of patients in the placebo group.  No safety concerns resulted from ruxolitinib use.   

Ruxolitinib Use in Treatment of Severe COVID-19

The cytokine storm that characterizes COVID-19 may be able to be reduced with the monoclonal antibody, tocilizumab, that targets the IL-6 (Interleukin-6) pathway. 20 Patients were given tocilizumab in addition to normal routine treatment over a period of nine days during the month of February 2020 in two different hospitals located in China.  
Results: 
- fever returned to normal within the first day
- After 5 days of treatment with tocilizumab, 75% of the patients experienced improved oxygen intake on their own, and 1 patient no longer needed oxygen therapy. 
- The percentage of lymphocytes in peripheral blood, (the blood that travels through the heart, arteries, capillaries and veins) was abnormal in 85% of patients before treatment with tocilizumab, but returned to normal in 52.6% of patients within 5 days of treatment with tocilizumab. 
- C-reactive protein significantly decreased in 84.2% of patients after 5 days, signifying reduced inflammation. 
- All 20 patients were discharged after 15 days of taking tocilizumab. 
- The preliminary data demonstrates that tocilizumab could be an effective treatment for patients with severe cover-19. 


Tocilizumab for effective treatment of patients with severe COVID-19

In addition to the milder situation treatments, it often requires hospitalization and advanced ventilatory support.

University of Michigan - Ann Arbor

Severe COVID-19 is a medical emergency and requires immediate hospitalization.

1. Severe dyspnea

2. Hypoxia

3. Serious dehydration

4. P/F ration < 300

5. New bilateral infiltrated on imaging

6. Altered level of consciousness (e.g., confusion, delirium, lethargy)*

*If this symptom is present, emergency medical attention should be sought right away, even if other symptoms are absent. Often times, this is the only severe symptom and can be present even when other "classic" COVID symptoms are absent. Even if this doesn't indicate COVID infection, it should still be treated as a medical emergency.


Severe COVID-19 symptoms

Currently, there is no FDA-approved, consistent treatment plan for COVID-19. Treatment depends on the severity of disease, the patient's ability to self-isolate, and the presence of other risk factors. Individuals with mild to moderate cases of COVID-19 are able to treat themselves at home without hospitalization or clinical care. If an individual is hospitalized, treatments will focus on managing the most common and severe COVID-19 complications. 

Therapeutic Treatment of COVID-19

1. [MODULE 1: From Bench to Bedside, Section: 'GRAPHIC SUMMARY' (as of March 19, 2020)](https://docs.google.com/document/d/1gjUuqTLi7xqMVzgWeYAFulmaIiKzhYY89PVOJJVvlNo/edit#heading=h.gtn0tdsnrc43)
2. [MEDICAL STUDENT COVID-19 CURRICULUM](https://docs.google.com/document/d/13JfRRw1GEIKz4JCde8WcQBCHnu-7nn11P_z0dHov1eA/preview)


COVID-19 Graphical Summary

- Pneumonia,
- Hypoxemic respiratory failure/ARDS,
- Sepsis and septic shock,
- Cardiomyopathy and arrhythmia,
- Acute kidney injury,
- Complications from prolonged hospitalization including:
   - Secondary bacterial infections,
   - Thromboembolism,
   - Gastrointestinal bleeding,
   - Critical illness polyneuropathy/myopathy.
- Neurological Symptoms (acute cerbrovascular diseases, impaired consciousness, skeletal muscle injury)
- COVID‐19‐associated pulmonary aspergillosis (CAPA)


Severe COVID-19 Case Complications

Treatment of Severe COVID-19

- NOTE: Some people (especially elderly people or people with serious underlying conditions) develop confusion/delirium, even though they don't have any of the typical COVID-19 symptoms. Although they may not be "screened" for COVID, they NEED immediate medical attention. 
- Altered mental status can be an independent predictor of mortality, even when other symptoms are not severe.
- Even if something other than COVID-19 caused the patient to have an altered mental status, emergency medical attention is still NEEDED.
-Sources: https://www.medpagetoday.com/infectiousdisease/covid19/90354; https://pubmed.ncbi.nlm.nih.gov/33566314/; https://www.cidrap.umn.edu/news-perspective/2020/11/delirium-fairly-common-older-covid-19-patients

Altered Mental Status indicates severe COVID-19

1- 14 day home quarantine from the day of exposure

2- Droplet, eye, and contact precautions, where appropriate for providers

3- Return precautions

4- Supportive care: encourage eating and drinking, acetaminophen for comfort/fever

5- Many hospitals are avoiding or cautious ibuprofen due to theoretical risk, but there is no scientific evidence about a link between COVID-19 and NSAIDS (03.25.2020)

Treatment of Mild COVID-19

1. Airborne precautions for aerosolizing procedures
2. Supportive care: acetaminophen for comfort/fever
3. Respiratory support
4. ARDS treatment as needed
5. Treat comorbidities
   - Suspected sepsis: empiric antibiotics
   - Flu: oseltamivir
   - Asthma/COPD: bronchodilators MDI

Treatment of Moderate COVID-19

In addition to milder case treatments, it requires circulatory support with fluid and vasopressors if clinically appropriate.

Treatment of Critical COVID-19

- Drugs
- Antiviral Treatments
- Drug-Drug Interactions of Proposed Treatments
- Traditional Treatments
- COVID-19 Pharmacokinetics

Interventions for COVID-19 treatment

As of today there are no antiviral therapies available for the treatment of COVID-19. However, there have been identified some potential druggable targets.

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