Treatments for mild COVID-19: Cochrane evidence

Sarah Chapman and Selena Ryan-Vig highlight Cochrane evidence on treatments that have been investigated for people with mild COVID-19.

The blog will be kept up to date with the most recent version of each Cochrane Review. This is a fast-moving field. You can view NICE’s rapid guideline on managing COVID-19 for the latest information about treating COVID in the UK. You can also view the living guideline by topic area.

You can either scroll through this page or click on any of the links below to jump to the relevant section. You can also read our blog on treatments for moderate to severe COVID-19: Cochrane evidence.

Page last updated: 24 June 2022, to include new evidence on ivermectin.

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Antibiotics (Azithromycin)

Key messages 

  • For people with mild COVID-19, treated as outpatients, azithromycin may have little to no benefit.
  • The evidence about possible serious harms is uncertain.
  • There is not enough information about possible mild side effects, heart rhythm problems, or quality of life.

The evidence

The evidence comes from the Cochrane Review Antibiotics for the treatment of COVID‐19 (published October 2021). Four studies compared antibiotics with placebo (a dummy treatment that looks the same as the medicine but lacks the active ingredient), standard care alone or another antibiotic in people with mild COVID-19. Seven other studies looked at people with moderate-to-severe COVID-19. (Read more: Treatments for moderate to severe COVID-19: Cochrane evidence). Azithromycin was the only antibiotic investigated so we do not know the effects of other antibiotics for treating COVID-19.

Potential relevance of this treatment for COVID-19

Antibiotics are cheap medicines, widely used to treat bacterial infections. Antibiotics have been studied as a potential treatment for COVID-19. This is because some laboratory studies have suggested that some antibiotics slow the reproduction of certain viruses, including SARS-CoV-2, the virus that causes COVID-19. There has been particular interest in one antibiotic, azithromycin, as some laboratory studies have indicated it may reduce inflammation and viral activity. But we need good evidence before using antibiotics for COVID-19. This is because overuse and/or misuse of antibiotics can lead to ‘antimicrobial resistance’ where, ultimately, antibiotics stop working.

Find out more

Colchicine

Key message

In non‐hospitalised people with no symptoms or mild COVID‐19, it is uncertain whether colchicine prevents deaths or side effects. However, it probably slightly reduces the risk of hospitalisation and serious side effects.

The evidence

The evidence comes from the Cochrane Review Colchicine for the treatment of COVID‐19 (published October 2021). It includes four studies (three with 11,525 hospitalised people and one with 4488 non‐hospitalised people). The study in non-hospitalised people compared colchicine to placebo or standard care alone. There are many ongoing studies that may help give a clearer answer about the possible benefits and harms of colchicine. The reviewers are searching for new evidence on a weekly basis and will update the review when they identify new, relevant evidence.

Potential relevance of this treatment for COVID-19

Colchicine is an anti‐inflammatory drug used to reduce swelling and inflammation. It is often used to treat gout, a condition where people’s joints become painful and swollen. Researchers are interested in colchicine as a possible COVID-19 treatment as it might help reduce inflammation caused by COVID-19. It is also important to know about its possible side effects, as it is known that colchicine may be harmful to people with certain health conditions, such as kidney or liver problems, or if you take too much of it.

Find out more

Convalescent plasma

Key message

The effects of convalescent plasma on people with mild COVID‐19 are uncertain.

The evidence

The evidence is from a Cochrane Review Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a living systematic review (last updated May 2021). For people with mild COVID-19 illness, there was just one small study (160 people) to include in the review. There is reliable evidence from 12 studies on people with moderate-to severe COVID-19. (Read more: Treatments for moderate to severe COVID-19: Cochrane evidence).

Potential relevance of this treatment for COVID-19

People who have recovered from a viral infection carry virus-specific antibodies in their blood plasma. Convalescent plasma (plasma from people who have recovered from the viral infection) has been used effectively to treat some treat viral infections. This has led some researchers to consider convalescent plasma as a potential treatment for COVID-19.

Find out more

Inhaled corticosteroids

Key message

For people with mild COVID-19 infection, compared with usual care or placebo, inhaled corticosteroids (budesonide or ciclesonide):

  • probably reduce the risk of admission to hospital or of dying up to day 30
  • probably increase the likelihood that COVID‐19 symptoms will have gone by day 14 and may shorten the time it takes for symptoms to go away
  • may make little to no difference to death from any cause up to day 30
  • may make little to no difference to the number of any unwanted effects or additional infections

The evidence is very uncertain potential serious harms of inhaled corticosteroids.

The evidence

The evidence comes from the Cochrane Review Inhaled corticosteroids for the treatment of COVID‐19 (published March 2022). It includes three studies with 3607 people, of whom 2490 had confirmed mild COVID-19. Most were aged over 50 and had other health problems such as lung disease or high blood pressure. The studies took place in high income countries before wide-scale COVID-19 vaccination programmes. The inhaled steroids used in the studies were budesonide and ciclesonide, compared with placebo or usual care.

The review authors found no data for people without symptoms and no studies of this treatment in people with moderate to severe COVID-19.

Potential relevance of this treatment for COVID-19

Inhaled corticosteroids are medicines that are breathed into the lower airways through an inhaler where they reduce inflammation in the lungs. They are used to treat inflammatory respiratory conditions like asthma and chronic obstructive pulmonary disease. They might have the potential to reduce the risk of severe COVID‐19 illness.

Find out more

 

Ivermectin

Key message

“We found no evidence to support the use of ivermectin for treating COVID‐19 or preventing SARS‐CoV‐2 infection. The evidence base improved slightly in this update, but is still limited.”

The evidence

The evidence comes from the Cochrane Review Ivermectin for preventing and treating COVID‐19 (updated June 2022). It includes 11 trials with 3409 participants investigating ivermectin plus standard of care compared to standard of care plus/minus placebo. The review authors excluded seven trials that were in the previous version of the review (not prospectively registered or non-randomised) and included four new ones.

The review authors conclude:

“For outpatients, there is currently low‐ to high‐certainty evidence that ivermectin has no beneficial effect for people with COVID‐19.” They also say “In this update, certainty of evidence increased through higher quality trials including more participants. According to this review’s living approach, we will continually update our search.”

Potential relevance of this treatment for COVID-19

Ivermectin, a medicine used to treat parasites, has been found in laboratory tests to slow the reproduction of the COVID-19 (SARS-CoV-2) virus, but very big doses would be needed in humans to have this effect.

Monoclonal antibodies

Key message

“…current evidence is insufficient to draw meaningful conclusions” about whether monoclonal antibodies are an effective and safe treatment for COVID-19.

The evidence

This evidence comes from the Cochrane Review SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19 (published September 2021). There were four studies with people with COVID-19 who were not in hospital, and two studies with hospitalised people. Commenting on the evidence gap, the review authors also noted that there are 36 ongoing studies which they hope will address these uncertainties.

Potential relevance of this treatment for COVID-19

Antibodies are made by the body as a defence against disease. They can also be produced in a laboratory, from cells taken from people who have recovered from a disease.

Antibodies that are designed to target only one specific protein – in this case, a protein on the virus that causes COVID‐19 – are ‘monoclonal’. They attach to the COVID‐19 virus and stop it from entering and reproducing in human cells. This may help to fight the infection.

Find out more

Vitamin D supplementation

Key message

The benefits and harms of vitamin D supplementation as a treatment of COVID‐19 are uncertain.

The evidence

The Cochrane Review on Vitamin D supplementation for the treatment of COVID‐19: a living systematic review (published May 2021) includes just three studies with 356 people with COVID-19 (including asymptomatic, mild, moderate and severe disease), comparing vitamin D supplementation with placebo or ‘standard care’. Only one of these studies looked at patients with mild illness and the study did not give any information about the outcomes of interest (such as effects on patients’ condition, or possible side effects).

The authors found 21 ongoing studies and three completed studies without published results, so their findings are likely to change when the review is updated.

Potential relevance of this treatment for COVID-19

The review authors explain: “Vitamin D is important for healthy bones, teeth and muscles. It helps to regulate blood sugar, the heart and blood vessels, and the lungs and airways. It also has a role in boosting the body’s immune system. These are areas affected by COVID‐19, so giving vitamin D to people with COVID‐19 might help them to recover more quickly or have the disease less severely.”

Find out more

 

Join in the conversation on Twitter with @CochraneUK or leave a comment on the blog. Please note, we cannot give specific medical advice and do not publish comments that link to individual pages requesting donations or to commercial sites, or appear to endorse commercial products. We welcome diverse views and encourage discussion but we ask that comments are respectful and reserve the right to not publish any we consider offensive. Cochrane UK does not fact check – or endorse – readers’ comments, including any treatments mentioned.

References (pdf)

Sarah Chapman and Selena Ryan-Vig have nothing to disclose.



Treatments for mild COVID-19: Cochrane evidence by Sarah Chapman and Selena Ryan-Vig

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

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