Treatment and management of COVID-19

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The management of COVID-19 includes supportive care, which may include fluid therapy, oxygen support, and supporting other affected vital organs.[1][2][3] The WHO is in the process of including dexamethasone in guidelines for treatment for hospitalized patients, and it is recommended for consideration in Australian guidelines for patients requiring oxygen.[4][5] CDC recommends those who suspect they carry the virus wear a simple face mask.[6] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.[7][8] Personal hygiene and a healthy lifestyle and diet have been recommended to improve immunity.[9] Supportive treatments may be useful in those with mild symptoms at the early stage of infection.[10] Nasal breathing is suggested as such a procedure based on several peer reviewed studies.[11][12]

The WHO, the Chinese National Health Commission, and the United States' National Institutes of Health have published recommendations for taking care of people who are hospitalised with COVID‑19.[13][14][15] Intensivists and pulmonologists in the U.S. have compiled treatment recommendations from various agencies into a free resource, the IBCC.[16][17]

Treatment[edit]

See also: Coronavirus disease 2019 § Research
An exhausted anesthesiologist physician in Pesaro, Italy, March 2020

Antiviral medications are under investigation for COVID-19, though none have yet been shown to be clearly effective on mortality in published randomized controlled trials.[18]

Emergency use authorization for remdesivir was granted in the U.S. on 1 May, for people hospitalized with severe COVID-19.[19][20] The interim authorization was granted considering the lack of other specific treatments, and that its potential benefits appear to outweigh the potential risks.[19][21][22] In September 2020, following a review of later research, the WHO recommended that remdesivir not be used for any cases of COVID-19, as there was no good evidence of benefit.[23]

In severe cases, the use of corticosteroids can reduce the risk of death.[23]

Taking over-the-counter cold medications,[24] drinking fluids, and resting may help alleviate symptoms.[25] Depending on the severity, oxygen therapy, intravenous fluids, and breathing support may be required.[26] The safety and effectiveness of convalescent plasma as a treatment option requires further research.[27]

Other trials are investigating whether existing medications can be used effectively against COVID-19 or the immune reaction to it.[18][28] On 16 June, the RECOVERY Trial group released a statement that their preliminary results show low-dose dexamethasone reduces mortality in patients receiving respiratory support,[29] though previous reviews had suggested the use of steroids may worsen outcomes.[30] Demand for dexamethasone surged after publication of the preprint.[31] On 2 September 2020, the WHO recommended treatment with systemic steroids for patients with severe and critical symptoms, but continued to advise against their use for other patients.[32]

A study of major hospitals in the U.S. found that abnormal liver tests occurred in most hospitalized patients with COVID-19 and may be associated with poorer clinical outcomes.[33] Tocilizumab was significantly associated in the relationship between the drugs used to treat the disease and abnormal liver tests, which prompted studies to determine whether abnormal results were due to coronavirus or drug-induced liver injury, according to Michael Nathanson, director of the Yale Liver Center and co-author of the study.[34]

Medications[edit]

See also: COVID-19 drug repurposing research and COVID-19 drug development

Numerous candidate medications are under investigation, but dexamethasone and remdesivir are the only medications with proven clinical benefit in randomized controlled trials.[35][36]

Systemic corticosteroids[edit]

Dexamethasone may be used for people requiring supplemental oxygen only. Following an analysis of seven randomized trials,[37] the WHO recommends the use of systemic corticosteroids in guidelines for treatment of people with severe or critical illness, and that they not be used in people that do not meet the criteria for severe illness.[38]

Remdesivir[edit]

In November 2020, the World Health Organization updated its guideline on therapeutics for COVID-19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO Solidarity trial.[39][40][needs update]

In November 2020, the FDA issued an emergency use authorization (EUA) for the combination of baricitinib with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized people two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[41] The data supporting the EUA for baricitinib combined with remdesivir are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the National Institute of Allergy and Infectious Diseases (NIAID).[41] The EUA was issued to Eli Lilly and Company.[41]

For symptoms[edit]

For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use.[42][43][44] The WHO and NIH do not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms,[13][45] and the FDA says currently there is no evidence that NSAIDs worsen COVID‑19 symptoms.[46]

While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications.[13][47][48][49] One study from 22 April found that people with COVID‑19 and hypertension had lower all-cause mortality when on these medications.[50]

Vitamin D[edit]

There has been particular interest given the significant overlap in the risk factors for severe COVID-19 and vitamin D deficiency, including obesity, older age, and Black or Asian ethnic origin, noting that vitamin D deficiency is common in Europe and the United States particularly within these groups.[51] The general recommendation to take vitamin D supplements, particularly given the levels of vitamin D deficiency in Western populations, has been repeated.[52]

There are a number of clinical trials being undertaken to examine any specific role for vitamin D in COVID-19 prevention and management.[53] Emerging results indicate a link between vitamin D deficiency and the severity of the disease. A systematic review and meta-analysis of 27 publications found that, although vitamin D deficiency was not associated with a higher probability of becoming infected with COVID-19, there were significant associations between vitamin D deficiency and the severity of the disease, including relative increases in hospitalization and mortality rates of about 80%.[54] As of October 2020 there has been no advisory recommendation to use vitamin D or its metabolites specifically for COVID-19 therapy.[52]

Other disease modifying treatments[edit]

Other disease modifying treatments under investigation but not recommended for use based on evidence as of July 2020 include Baloxavir marboxil, Favipiravir, Lopinavir/ritonavir, Ruxolitinib, Chloroquine, Hydroxychloroquine, Ivermectin, convalescent plasma, Interferon β-1a and colchicine.[5] The oral JAK inhibitor, Baricitinib is also being studied for COVID-19 treatment.[55]

Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).[56]

On 9 November 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients.[57] Monoclonal antibodies are laboratory-made proteins that mimic the immune system's ability to fight off harmful antigens such as viruses.[58]

On 21 November 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in people twelve years of age or older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19.[59] This includes those who are 65 years of age or older or who have certain chronic medical conditions.[59]

During pregnancy[edit]

To date, most SARS-CoV-2-related clinical trials have excluded, or included only a few, pregnant or lactating women. This limitation makes it difficult to make evidence-based therapy recommendations in these patients and potentially limits their COVID-19 treatment options. The US CDC recommends shared decision-making between the patient and the clinical team when treating pregnant women with investigational medication.[60]

Experimental treatments[edit]

Convalescent plasma collected at a blood donor center during the COVID-19 pandemic.

Antiviral medications[edit]

Research into potential treatments started in January 2020,[61] and several antiviral drugs are in clinical trials.[62][63] Remdesivir appears to be the most promising.[18] Although new medications may take until 2021 to develop,[64] several of the medications being tested are already approved for other uses or are already in advanced testing.[65] Antiviral medication may be tried in people with severe disease.[1] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[66]

Convalescent plasma[edit]

Convalescent plasma is plasma from the blood of people who have recovered from COVID-19 that contains COVID-19 antibodies.[67][needs update] The FDA has granted temporary authorisation to convalescent plasma as an experimental treatment in cases where the person's life is seriously or immediately threatened.[68] Convalescent plasma treatment has not undergone the randomized controlled or non-randomized clinical studies needed to determine if is safe and effective for treating people with COVID-19.[67][69][70]

Protective equipment[edit]

See also: Shortages related to the COVID-19 pandemic
The U.S. Centers for Disease Control and Prevention (CDC) recommends four steps to putting on personal protective equipment (PPE).[71]

Precautions must be taken to minimise the risk of virus transmission, especially in healthcare settings when performing procedures that can generate aerosols, such as intubation or hand ventilation.[72] For healthcare professionals caring for people with COVID‑19, the CDC recommends placing the person in an Airborne Infection Isolation Room (AIIR) in addition to using standard precautions, contact precautions, and airborne precautions.[73]

The CDC outlines the guidelines for the use of personal protective equipment (PPE) during the pandemic. The recommended gear is a PPE gown, respirator or facemask, eye protection, and medical gloves.[74][75]

When available, respirators (instead of face masks) are preferred.[76] CDC recommends mask use in public places, when not able to social distance, and while interacting with people outside of those that the person lives with.[77] N95 respirators are approved for industrial settings but the FDA has authorised the masks for use under an emergency use authorization (EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific biological agent is not guaranteed for off-label uses.[78] When masks are not available, the CDC recommends using face shields or, as a last resort, homemade masks.[79]

Respiratory support[edit]

Mechanical ventilation[edit]

See also: Shortages related to the COVID-19 pandemic § Mechanical ventilation

Most cases of COVID‑19 are not severe enough to require mechanical ventilation or alternatives, but a percentage of cases are.[80][81] The type of respiratory support for individuals with COVID‑19 related respiratory failure is being actively studied for people in the hospital, with some evidence that intubation can be avoided with a high flow nasal cannula or bi-level positive airway pressure.[82] Whether either of these two leads to the same benefit for people who are critically ill is not known.[83] Some doctors prefer staying with invasive mechanical ventilation when available because this technique limits the spread of aerosol particles compared to a high flow nasal cannula.[80]

Mechanical ventilation had been performed in 79% of critically ill people in hospital including 62% who previously received other treatment. Of these 41% died, according to one study in the United States.[84]

Severe cases are most common in older adults (those older than 60 years,[80] and especially those older than 80 years).[85] Many developed countries do not have enough hospital beds per capita, which limits a health system's capacity to handle a sudden spike in the number of COVID‑19 cases severe enough to require hospitalisation.[86] This limited capacity is a significant driver behind calls to flatten the curve.[86] One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died.[7] In China, approximately 30% of people in hospital with COVID‑19 are eventually admitted to ICU.[87]

Acute respiratory distress syndrome[edit]

Main article: Acute respiratory distress syndrome

Mechanical ventilation becomes more complex as acute respiratory distress syndrome (ARDS) develops in COVID‑19 and oxygenation becomes increasingly difficult.[88] Ventilators capable of pressure control modes and high PEEP[89] are needed to maximise oxygen delivery while minimising the risk of ventilator-associated lung injury and pneumothorax.[90] High PEEP may not be available on older ventilators.[citation needed]

Options for ARDS[88]
Therapy Recommendations
High-flow nasal oxygen For SpO2 <93%. May prevent the need for intubation and ventilation
Tidal volume 6mL per kg and can be reduced to 4mL/kg
Plateau airway pressure Keep below 30 cmH2O if possible (high respiratory rate (35 per minute) may be required)
Positive end-expiratory pressure Moderate to high levels
Prone positioning For worsening oxygenation
Fluid management Goal is a negative balance of 0.5–1.0L per day
Antibiotics For secondary bacterial infections
Glucocorticoids Not recommended

Extracorporeal membrane oxygenation[edit]

Main article: Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is an artificial lung technology that has been used since the 1980s to treat respiratory failure and acute respiratory distress syndrome when conventional mechanical ventilation fails. In this complex procedure, blood is removed from the body via large cannulae, moved through a membrane oxygenator that performs the lung functions of oxygen delivery and carbon dioxide removal, and then returned to the body. The Extracorporeal Life Support Organization (ELSO) maintains a registry of outcomes for this technology, and it has been used in >120,000 patients over 435 ECMO centers worldwide with 40% mortality for adult respiratory patients.[91]

Initial use of ECMO in COVID-19 patients from China early in the pandemic suggested poor outcomes, with >90% mortality.[92] In March 2020, the ELSO registry began collecting data on the worldwide use of ECMO for patients with COVID-19 and reporting this data on the ELSO website in real time. In September 2020, the outcomes of 1,035 COVID-19 patients supported with ECMO from 213 experienced centers in 36 different countries were published in The Lancet, and demonstrated 38% mortality, which is similar to many other respiratory diseases treated with ECMO. The mortality is also similar to the 35% mortality seen in the EOLIA trial, the largest randomized controlled trial for ECMO in ARDS.[93] This registry based, multi-center, multi-country data provide provisional support for the use of ECMO for COVID-19 associated acute hypoxemic respiratory failure. Given that this is a complex technology that can be resource intense, guidelines exist for the use of ECMO during the COVID-19 pandemic.[94][95][96]

Psychological support[edit]

See also: Mental health during the COVID-19 pandemic

Individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of the infection itself. To address these concerns, the National Health Commission of China published a national guideline for psychological crisis intervention on 27 January 2020.[97][98]

The Lancet published a 14-page call for action focusing on the UK and stated conditions were such that a range of mental health issues was likely to become more common. BBC quoted Rory O'Connor in saying, "Increased social isolation, loneliness, health anxiety, stress, and an economic downturn are a perfect storm to harm people's mental health and wellbeing."[99][100]

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External Links[edit]

Treatment guidelines[edit]

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