COVID-19 evidence: a Cochrane round-up

Sarah Chapman and Selena Ryan-Vig highlight Cochrane evidence on COVID-19 and other health effects of the pandemic, with links to reviews, blogs and other Cochrane resources.  

This blog was last updated on 14 January 2022.

While we’ve all been adapting to huge and sudden changes in our lives and healthcare workers have been meeting unprecedented challenges, scientists have scrambled to produce research evidence relevant to the pandemic. Cochrane is responding by producing rapid reviews of this new evidence on priority topics, and these are updated as new evidence emerges. They show that much of the research that has been done so far leaves us with more unanswered questions than answers, but we must hope that this changes as new studies are available to add to the reviews.

Here’s a round-up of some of the Cochrane evidence so far. On this page, there are sections on:

Detecting COVID-19

Signs and symptoms of COVID-19

We’re hearing a lot about temperature checks, which in many places are being used determine whether someone may enter a care home, hairdressers or other building. But what’s the evidence? We’ve blogged about a Cochrane Review, first published in July 2020 and updated in February 2021, on the accuracy of any signs and symptoms, either alone or in combination, for diagnosing COVID‐19.

Take-home points: A Cochrane Review on the accuracy of clinical signs and symptoms for diagnosing COVID-19 has been updated, with more studies and better quality evidence. It confirms that a single symptom or sign cannot accurately diagnose COVID-19. However, loss of taste or smell, high temperature, or cough may be useful to identify people who might have COVID-19, prompting further testing. There is a need for evidence on combinations of signs and symptoms and in different settings (particularly GP practices) and age groups (children, older adults).

You can read the blog: “Signs and symptoms of COVID-19: new Cochrane evidence“. There is also a podcast.

Antibody tests for COVID-19

Antibody tests have the potential to identify people who have had COVID-19. A Cochrane Review ‘Antibody tests for identification of current and past infection with SARS-CoV-2′ was published in June 2020 and we have blogged about it: “Antibody tests for COVID-19: new evidence on test accuracy and some considerations“.

Take-home pointsAntibody tests have the potential to identify people who have had COVID-19.A Cochrane Rapid Review shows that antibody tests could have a useful role in detecting if someone has had COVID-19. As with any diagnostic test, there will be a number of people falsely diagnosed as having COVID-19, and a number of people who do have the disease will be missed; timing makes a big difference to the accuracy of the test.Test accuracy is only one consideration in decisions about the purposes and implications of widespread testing for COVID-19 antibodies.

Rapid point-of-care tests for diagnosing COVID-19 infection

Tests for diagnosing COVID-19 infection are important tools for helping reduce the spread of infection in communities, schools and workplaces, and have received a huge amount of attention in the press and on social media over the last year. The Cochrane Review Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection, was updated for the first time in March 2021. The review looks at two types of test, antigen tests (including lateral flow tests or LFTs) and molecular tests. Both types of test use swab samples taken from the nose or throat, can be used outside of a specialist laboratory and provide results in less than two hours.

Lead author, Jac Dinnes, has written a blog Rapid point-of-care tests for diagnosing COVID-19 infection: the latest Cochrane evidence to help health care professionals and members of the public interpret the evidence for their accuracy.

Most of the evidence for the diagnostic accuracy of lateral flow tests (LFTs) for COVID-19 is based on studies in people with symptoms, but there is good reason to suspect that LFTs are not as accurate when used in people without symptoms The balance of benefits and harms from using LFTs changes depending on the number of people who really have COVID-19 infection in the populations being tested (prevalence) Decisions to implement lateral flow testing should be informed by the best available evidence for how well tests perform in different populations and testing scenarios

Routine laboratory tests – how good are they for detecting COVID-19?

Routine blood tests, processed in laboratories, include counts of different types of white blood cells that help fight infection and identifying proteins (‘markers’) that can indicate general inflammation and organ damage. These are widely available and in some places might be the only tests available for diagnosing COVID-19.

A Cochrane Review Routine laboratory testing to determine if a patient has COVID‐19 (November 2020) has looked for evidence on the accuracy of these tests in people with suspected COVID-19 for diagnosing the disease and for prioritizing people for different levels of treatment. The review includes 21 studies looking at 67 routine laboratory tests for COVID-19, all in people who were patients in hospitals.

The bottom line: “Although these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID‐19 on their own.”

Screening for COVID-19

Screening people who have mild or no symptoms but have COVID-19, to find out if someone’s infected, is another strategy that has potential to help reduce the spread of infection, as those who are found to have the virus could then isolate, for example. A Cochrane rapid review on universal screening for SARS‐CoV‐2 infection was published in September 2020. The evidence base is currently very limited and highlights uncertainty about the effectiveness of screening for COVID-19. The review finds that:

“One‐time screening in apparently healthy people is likely to miss people who are infected. We are unsure whether combined screenings, repeated symptom assessment, or rapid laboratory tests are useful.

As more people become infected, screening will identify more cases. However, because screening can miss people who are infected, public health measures such as face coverings, physical distancing, and quarantine for those who are apparently healthy, continue to be very important.”

Here is a video summary.

Thoracic (chest) imaging tests for COVID-19

A Cochrane Review on thoracic imaging tests for the diagnosis of COVID-19 was published in September 2020 and updated for a second time in March 2021. It brings together evidence on the diagnostic accuracy of chest (thoracic) imaging (computed tomography (CT), X‐ray and ultrasound) in people with suspected COVID‐19. This is one of a suite of Cochrane ‘living systematic reviews’ summarising evidence on the accuracy of different imaging tests and diagnostic features in people regardless of their symptoms, grouped according to the research questions and settings.

The review includes 51 studies involving 19,775 people with suspected COVID-19, of whom just over half had a final diagnosis of COVID-19. Most of the studies looked at chest CT. The evidence so far suggests that chest CT is better at ruling out COVID-19 infection than distinguishing it from other respiratory problems. So, its usefulness may be limited to excluding COVID‐19 infection rather than distinguishing it from other causes of lung infection. However, the authors’ confidence in the evidence is limited because the studies differed from each other, used different methods to report their results and very few studies directly compared one type of imaging test with another.

Measures to control the spread of COVID-19

School-based measures to contain the COVID-19 pandemic

Shutting schools was one of the earliest responses to the pandemic in many countries. As well as potential benefits of this strategy for limiting the spread of infection there are many potential harms, including worsening health and wellbeing for children and widening inequalities. Alternatives to school closure are also being adopted, including the wearing of face masks, hand hygiene, changes to school activities, improved ventilation systems and screening. It will be important to have evidence of the effectiveness of these different measures to inform policy and practice.

Cochrane has published a scoping review on measures implemented in the school setting to contain the COVID‐19 pandemic (December 2020), to map the existing evidence. The review authors found 42 studies, of which 31 were mathematical modelling studies, evaluating a wide range of measures. This will form the basis of a review of the effectiveness of these measures.

Quarantine for controlling COVID-19

A Cochrane rapid review on quarantine alone or in combination with other public health measures to control COVID-19 was published in April 2020 and updated in September 2020. It is the focus of this blog: “Quarantine for controlling COVID-19 (coronavirus). New Cochrane evidence.”

A Cochrane Rapid Review, updated in September 2020, has found that COVID-19 mathematical modelling studies consistently report a benefit of quarantine in reducing the number of people who get infected with COVID-19 and who die from it. The number of studies has increased significantly in a short space of time since this review was first published in April 2020, but the evidence base is still limited. This is because most studies on COVID-19 are mathematical modelling studies that make different, important assumptions (for example, about how quickly the virus would spread). This Rapid Review was done in a short space of time as part of Cochrane’s organizational effort to meet the need for up-to-date summaries of evidence to support decision-making in combating the effects and impact of COVID-19. More Rapid Reviews, answering other important questions about COVID-19, are underway.

Watch a video of the lead author summarising the review’s findings. You might also be interested in this blog ““Stay at home” rules: what makes people more likely to stick to quarantine?“, which looks at two non-Cochrane rapid reviews from researchers at King’s College London.

Contact tracing

Contact tracing aims to reduce transmission of infection by identifying people who have been in contact with someone who has it, so that they can isolate. A Cochrane rapid review published in August 2020 looked at evidence on digital contact tracing technologies in epidemics.

The review highlights an evidence gap, the authors concluding that “the effectiveness of digital solutions is largely unproven as there are very few published data in real‐world outbreak settings.”

Personal Protective Equipment (PPE) for healthcare workers

Two Cochrane reviews contribute to the evidence base on PPE for healthcare workers and we have a blog about these: “Personal protective equipment (PPE) for healthcare workers: new Cochrane evidence“. They look at Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff (May 2020) and Barriers and facilitators to healthcare workers’ adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis (April 2020).

Take-home points • An updated review and a new rapid review on PPE have been produced as part of Cochrane’s organizational effort to meet the need for up-to-date summaries of evidence to support decision-making in combating the effects and impact of COVID-19. • These reviews contribute to the evidence base about a range of considerations in PPE use, including barriers and facilitators to healthcare workers adherence to infection prevention and control guidelines. There are some new, creative solutions being developed to address some of the issues associated with wearing PPE.

For the review on PPE there is a Cochrane Clinical Answer. For the review on barriers and facilitators there is podcast and a Cochrane Clinical Answer. Evidence Synthesis Ireland and Cochrane Ireland have also created an infographic summarising key messages.

Preventing or reducing COVID-19 infections in long term care facilities (care homes)

A Cochrane Review ‘Can non‐medicinal measures prevent or reduce SARS‐CoV‐2 infections in long term care facilities?’ (published September 2021) included 22 studies exploring this question. 11 of the studies were observational, i.e. they used real-world data, and 11 were modelling studies, i.e. they used mathematical prediction.

There were four main types of measures.

1) Entry regulation measures to prevent residents, staff or visitors introducing the virus into the facility

Examples include: staff confining themselves with residents, quarantine for newly‐admitted residents, testing new admissions, not allowing the admission of new residents, and preventing visitors from entering facilities.

Most studies showed such measures may be beneficial, but some studies found that there may be no little or no effect or unwanted effects, such as delirium and depression among residents when visitors were restricted.

For more information: What are the effects of COVID‐19 entry regulation measures in long‐term care facilities (LTCFs)?

2) Contactregulating and transmissionreducing measures to prevent people passing on the virus

Examples include: wearing masks or personal protective equipment (PPE), social distancing, extra cleaning, reducing contact between residents and among staff, and placing residents and staff in care groups and limiting contact between groups.

Some measures may be beneficial, but the evidence is often very uncertain.

For more information: What are the effects of contact regulation and transmission‐reducing measures on COVID‐19 in long‐term care facilities (LTCFs)?

3) Surveillance measures designed to identify an outbreak early

Examples include: regular testing of residents or staff regardless of symptoms, and symptom‐based testing

Routine testing of residents and staff may reduce the number of infections, hospitalisations, and deaths among residents (although the evidence on the number of deaths among staff was less clear).

Testing more often, getting test results faster, and using more accurate tests may have more beneficial effects.

For more information: What are the effects of COVID‐19 surveillance measures in long‐term care facilities (LTCFs)?

4) Outbreak control measures to reduce the consequences of an outbreak

Examples include: isolation of infected residents, and separating infected and non‐infected residents or staff caring for them.

These measures may reduce the number of infections and the risk of outbreaks in facilities, but often the evidence is very uncertain.

For more information: What are the effects of COVID‐19 outbreak control measures in long‐term care facilities (LTCFs)?

A combination of different measures may be effective in reducing the number of infections and deaths.

Antimicrobial mouthrinses and nasal sprays to protect healthcare workers and patients at risk of COVID-19

Antimicrobial mouthrinses and nasal sprays have the potential to help people with COVID-19 fight infection and prevent them infecting healthcare workers who care for them. They might also offer some protection to healthcare workers, especially if they use them before doing aerosol-generating procedures, such as drilling teeth.

Three new Cochrane Reviews were published in September 2020 looking at different aspects of this. There is a helpful summary of all three in this Cochrane Oral Health Editorial base blog Antimicrobial mouthrinses and nasal sprays to protect healthcare workers and patients at risk of COVID-19, which also has links to each of the reviews. No completed studies were found for any of the reviews, so this is currently an evidence gap, but there are ongoing studies for two of these three reviews and all will be updated.

A Cochrane rapid review, published in September 2020, looked at travel-related control measures to contain the COVID-19 pandemic. Not surprisingly, it highlighted uncertainty about their effectiveness and a lack of reliable and ‘real-life’ evidence. The review was updated in March 2021.

Jacob Burns, lead author of this update explains, “In this update we identified a much expanded evidence base related to international travel control measures to contain the COVID-19 pandemic, with 38 additional studies focusing on COVID-19 identified. Many of the studies were similar with regard to scope and methods, and overall the conclusions of the updated review remain largely the same. Some aspects of the evidence base, however, were improved – for example, we identified studies from further parts of the world that were not represented in the original review, including African and Eastern Mediterranean regions. Additionally, we identified more studies evaluating entry and/or exit screening measures at real-world ports of entry.” 

You can read about the review in this blog “Travel-related measures for controlling the spread of COVID-19: New Cochrane evidence“.

Treating people with COVID-19

Are antibiotics an effective treatment for COVID-19 and do they cause unwanted effects?

Antibiotics are cheap medicines, widely used to treat bacterial infections.

Recently, 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. However, 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.

The authors of the review Antibiotics for the treatment of COVID‐19 (published October 2021) found 11 studies with 11,281 people. The studies only investigated one antibiotic, azithromycin, so we do not know the effects of other antibiotics for treating COVID-19.

Only nine of the studies reported data that could be analysed. These studies (with 10,807 people) compared azithromycin to no treatment, placebo or usual care alone.

Main results

For inpatients with moderate-to-severe COVID-19:

  • Azithromycin does not lead to more or fewer deaths in the 28 days after treatment
  • Azithromycin probably does not:
    • worsen or improve patients’ condition
    • increase or decrease serious unwanted events, or heart rhythm problems
  • Azithromycin may increase non-serious unwanted effects slightly

No studies looked at quality of life.

Read more: For adults hospitalized with moderate to severe COVID‐19, what are the effects of azithromycin?

People with mild COVID-19:

For people with mild COVID-19 (or with no symptoms), treated as outpatients, azithromycin may have little to no benefit. The evidence about possible serious unwanted effects is uncertain. No studies reported on non-serious unwanted events, heart rhythm problems, or quality of life.

Read more: For adults with asymptomatic or mild COVID‐19, what are the effects of azithromycin?

The review authors found 19 ongoing studies that are investigating antibiotics for COVID-19 and will update this review soon.

However, given the current evidence and the threat of antimicrobial resistance, the authors say that “antibiotics should not be used for treatment of COVID-19 outside well-designed randomized controlled trials”.

Cardiovascular effects

A Cochrane Review COVID‐19 and its cardiovascular effects: a systematic review of prevalence studies (March 2021) has looked at both cardiovascular problems pre-existing the development of COVID-19 and assesses the risk of cardiovascular complications, highlighting which are the most common (unexpectedly, this was atrial fibrillation). Senior author Professsor John GF Cleland discusses it in this interview. He comments that “These results show what the clinical teams looking after patients with COVID should watch out for. Clinical teams are already aware of the risk of blood clots but may be less aware of the risk of developing atrial fibrillation or heart failure. Also, heart failure may be difficult to diagnose in a patient with COVID, so great care and attention is required not to miss this treatable diagnosis. ”

There is a Cochrane Clinical Answer for this review:  “What are the cardiovascular effects of COVID-19?” and a Cochrane Podcast:  What type of heart and blood vessel problems complicate COVID-19 infections, how common are they and what other medical conditions do these patients have?.

Care bundles for people with COVID-19 or related conditions in intensive care

Cochrane has published a scoping review on care bundles for improving outcomes in patients with COVID-19 or related conditions in intensive care (December 2020) to map the existing evidence, alongside a Cochrane Clinical Answer. The review authors found 21 studies and also identified three ongoing studies. Seven included patients with COVID-19. Most care bundles involved practices related to breathing support or ventilator settings, or the positioning of a patient, and COVID‐19‐specific studies also focused on infection control and use of personal protective equipment (PPE). There now needs to be a systematic review of this evidence.

Chloroquine or hydroxychloroquine for treatment of COVID‐19

 A Cochrane Review on Chloroquine or hydroxychloroquine for prevention and treatment of COVID‐19 brings together the available evidence from randomised trials on the effectiveness and safety of hydroxychloroquine (HCQ) for treating people with COVID-19 and preventing COVID-19 disease in people exposed to the virus (SARS‐CoV‐2). All the studies currently included in the review investigated hydroxychloroquine and not chloroquine. The review authors are also interested in the evidence on the use of these drugs for preventing COVID-19 disease in people at risk of exposure to the virus (such as healthcare workers), but there are no trial results ready to report for this.

When used to treat people with COVID-19, there is high-certainty evidence that HCQ makes little or no difference to the risk of dying from the disease, compared with standard care or placebo. There is moderate-certainty evidence that it probably does not reduce the chances of needing mechanical ventilation. The risks of adverse events are probably increased with HCQ. The effect of HCQ in preventing illness in people who have been exposed to the virus is very uncertain, but again it probably increases the risk of adverse events.

There is a Cochrane editorial on this review: Contested effects and chaotic policies: the 2020 story of (hydroxy) chloroquine for treating COVID‐19 (published March 2021) and also a Cochrane Clinical Answer: For adults with coronavirus disease 2019 (COVID-19), what are the benefits and harms of hydroxychloroquine?

Convalescent plasma – a possible treatment for COVID-19?

Many clinical trials are being done to investigate the potential benefits or harms of using plasma from people who have recovered from COVID-19 to treat people who are currently ill with it. This blog: “Convalescent plasma to treat people with COVID-19: the evidence so far” looks at a Cochrane rapid review on convalescent plasma to treat people with COVID-19, updated for the fourth time in May 2021. There is now high-certainty evidence that convalescent plasma has little to no benefit for the treatment of people with moderate to severe COVID‐19. You can also read an interview with Vanessa Piechotta, the lead author of the review. There is also a Cochrane Clinical Answer and a podcast.

A Cochrane rapid review (updated in May 2021) with 13 studies and 48,509 participants shows that convalescent plasma has little to no benefit for the treatment of people with moderate to severe COVID‐19. The effects of convalescent plasma for treating people with mild COVID‐19 or who have no symptoms are uncertain. The review is being regularly updated as a ‘living systematic review’, based on weekly searches for new evidence. The authors found about 130 ongoing, unpublished and recently published studies and will update the review with evidence from these studies soon.

Are laboratory‐made, COVID‐19‐specific monoclonal antibodies an effective treatment for COVID‐19?

A Cochrane Review SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19 (published September 2021) explored this question. It included 6 studies with 17,495 people (some of whom were hospitalised, others were not).

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.

Overall, the “current evidence insufficient to draw meaningful conclusions” about whether monoclonal antibodies are an effective and safe treatment for COVID-19. However, there are 36 ongoing studies which will hopefully address this uncertainty.

For more information, you can listen to this Cochrane podcast: Are laboratory-made, COVID-19-specific monoclonal antibodies an effective treatment for COVID-19?

Read these Cochrane Clinical Answers:

Is colchicine an effective treatment for people with COVID19?

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.

The Cochrane Review Colchicine for the treatment of COVID‐19 (published October 2021), includes four studies (three with 11,525 hospitalised people and one with 4488 non‐hospitalised people). Two studies compared colchicine plus usual care with usual care alone. The other two studies compared colchicine with usual care and placebo.

Key findings:

  • In hospitalised people with moderate-to-severe COVID19, colchicine probably has little to no benefit, and the evidence about its side effects is very uncertain.
  • In nonhospitalised people with no symptoms or mild COVID19, it is uncertain whether colchicine prevents deaths or side effects. However, it probably slightly reduces the risk of hospitalisation and serious side effects.

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.

Find out more:

Corticosteroids (antiinflammatory medicines) given orally or by injection

Corticosteroids are anti‐inflammatory medicines, commonly used to treat a variety of conditions. As the immune system fights COVID-19, the lungs and airways become inflamed, causing breathing difficulties. Corticosteroids are a possible treatment for COVID-19 because they may reduce this inflammation, thereby reducing the need for breathing support with a ventilator. Some patients’ immune systems overreact to the virus, causing further inflammation and tissue damage; corticosteroids may also help to control this response.

A Cochrane Review ‘Systemic corticosteroids for the treatment of COVID‐19’ (published August 2021) brings together the latest evidence on corticosteroids (mostly dexamethasone). The authors found 11 studies with 8075 people hospitalised with COVID‐19. (There is no evidence available about people without symptoms or with mild COVID‐19 who were not hospitalised).

Key findings:

  • Compared with placebo or usual care, corticosteroids probably slightly reduce the number of deaths from any cause, up to 60 days after treatment
  • Corticosteroids may improve people’s symptoms. (In one study, people on a ventilator at the start of the study were ventilation-free for more days with corticosteroids than with usual care)
  • However, it’s uncertain:
    • whether corticosteroids reduce the need for patients who are not already receiving ventilation to be put on a ventilator because the evidence is very limited
    • whether corticosteroids cause unwanted effects
    • which corticosteroid is the most effective

There are many ongoing studies. The review will be updated soon to include their findings and hopefully resolve some of these unanswered questions.

You can also see the NICE recommendations about corticosterioids in a rapid guideline on managing COVID-19 (see page 32), as well as a Cochrane Clinical Answer and a Cochrane podcast.

Interleukin‐6 blocking agents for treating COVID‐19

Interleukin-6 is a protein involved in immune responses. Medicines that block interleukin-6 are used to treat other conditions, like rheumatoid arthritis, that involve an ‘over-reactive’ immune system. They have been used for treating severe COVID-19 and a new Cochrane Review Interleukin‐6 blocking agents for treating COVID‐19: a living systematic review (published March 2021) has been done to look for evidence of its effectiveness and safety.

The review includes 10 studies with 6896 people with COVID-19 (average age 56 to 65 years), comparing one of two interleukin-6 blocking medicines, tocilizumab and sarilumab, with placebo (a dummy treatment that looks the same as the medicine but lacks the active ingredient) or ‘standard care’.

There is high-certainty evidence that treatment with tocilizumab reduced the number of people who died, of any cause, after 28 days. It probably makes little or no difference to time to leaving hospital or clinical symptoms. It probably slightly reduces the number of serious unwanted effects such as life-threatening conditions or death. Its effect on the severity of COVID-19 is uncertain. There is uncertainty about the effects of sarilumab, although the review authors report that it probably does not cause more unwanted effects (of any type) than placebo.

The review authors found some ongoing trials of interleukin-blocking medicines used to treat COVID-19 that haven’t yet reported results. This is a living systematic review and the results will be updated with new data as soon as possible.

You can read more in this Cochrane Clinical Answer: For adults with COVID-19, what are the effects of the interleukin-6 blocking agents tocilizumab and sarilumab?

Interventions for palliative symptom control in people with COVID-19

A Cochrane Review Interventions for palliative symptom control in COVID‐19 patients (August 2021), and its associated Cochrane Clinical Answer, has highlighted the need for evidence to guide healthcare staff and other caregivers caring for people dying from COVID-19, who may be experiencing distressing symptoms such as delirium and breathlessness. For this review, the authors identified just four retrospective cohort studies from the United Kingdom and Sweden. None of the studies included a comparator, or provided information on quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; or adverse events and serious adverse events. Nor were outcomes for symptom relief assessed by patients themselves. The review authors conclude “we cannot draw any conclusions about the effectiveness or safety [of interventions] based on the identified evidence” and will update the review when new evidence becomes available.

Commenting on the review, Scott Murray, Emeritus Professor of Primary Palliative Care (University of Edinburgh), said “However, it would be unethical to deny people dying of COVID-19 a palliative care approach as there is a great deal that is known about the general care of people with other conditions that could be applied to people with COVID-19. Also there is much evidence that a holistic approach to breathlessness improves quality of life. See:

Ivermectin for preventing and treating COVID‐19

The authors of a Cochrane systematic review Ivermectin for preventing and treating COVID‐19 (July 2021) found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, but the evidence base is limited.

Maria Popp and Stephanie Weibel, the main authors of the review, said: “The lack of good quality evidence on efficacy and safety of ivermectin arises from a study pool that consists mainly of small, insufficiently powered RCTs [randomized controlled trials] with overall limited quality regarding study design, conduct, and reporting. Current evidence does not support using ivermectin for treating or preventing of COVID-19 unless they are part of well-designed randomized trials.”

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. The authors found 31 ongoing studies which they will assess for inclusion in the review when the results become available.

There is a podcast. You can also read more in these two Cochrane Clinical Answers:

Oxygen therapy for adults in intensive care with acute respiratory distress syndrome

A Cochrane rapid review on oxygen targets in the intensive care unit during mechanical ventilation for acute respiratory distress syndrome has brought together evidence on this topic. The review authors explain the context:

“Acute respiratory distress syndrome (ARDS) is a very severe breathing problem with a high mortality rate (chance of dying). It has many potential causes, including viral infections such as COVID‐19, and there are no specific treatments for it except for giving patients oxygen via a ventilator (artificial breathing machine) on an intensive care unit, often for long periods of time. However, large amounts of oxygen (either a high concentration of oxygen or oxygen administered for a long period of time) are associated with increased harm due to other illnesses (e.g. heart attack or stroke).”

Here’s what they found:

Patients with acute respiratory distress syndrome (ARDS) and receiving oxygen through a breathing tube in intensive care may be more likely to survive beyond 90 days if they receive higher volumes of oxygen, compared with lower volumes. Whether patients receive a higher or lower volume of oxygen may make little or no difference to the number of days ventilated; the need for inotropic support (to stabilise circulation and optimise oxygen supply); or the likelihood of needing renal replacement therapy. However the evidence is very uncertain (all very low-certainty evidence). Effects on quality of life were not reported.The evidence is very uncertain about the potential harms of higher versus lower oxygen targets (very low-certainty evidence). Cochrane Review (published September 2020); one study with 205 mechanically ventilated patients in an intensive care setting, comparing conservative oxygen therapy with liberal oxygen therapy for seven days.

You may also be interested in recent Cochrane Reviews on High versus low positive end‐expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome (March 2021) and High‐flow nasal cannulae for respiratory support in adult intensive care patients (March 2021).

Prophylactic anticoagulants for people hospitalised with COVID-19

COVID‐19 may predispose people to getting blood clots in the arteries, veins and lungs. Venous and arterial thromboembolic complications affect 16% of people hospitalised with COVID‐19 and 31% to 49% of people with COVID‐19 in intensive care units, with 90% of such cases being venous thromboembolism. A Cochrane Review, Prophylactic anticoagulants for people hospitalised with COVID‐19, has looked for evidence on the effects of using blood thinning drugs to prevent this in people hospitalised with COVID-19.

As yet, there are no published randomised trials and the authors conclude that there is insufficient evidence to determine the risks and benefits of prophylactic anticoagulants in this population. However, they found 22 studies in progress which plan to evaluate 15,000 people, which will be considered for future updates of the review.

Find out more in this Cochrane Clinical Answer and a Cochrane podcast.

Remdesivir for the treatment of COVID-19

Remdesivir is a medicine that fights viruses. It has been found to stop the virus that causes COVID-19 from reproducing. A Cochrane Review Remdesivir for the treatment of COVID-19 (August 2021) has looked for evidence on its use to treat people with COVID-19.

The review authors found that for adults hospitalised with COVID-19 remdesivir probably has little or no effect on deaths from any cause up to 28 days after treatment compared with placebo (sham treatment) or usual care. They are uncertain whether remdesivir improves or worsens patients’ condition, based on whether they needed more or less help with breathing.

You can find out more in this news item Remdesivir for the treatment of COVID-19, this podcast, and in this Cochrane Clinical Answer: What are the effects of remdesivir for the treatment of COVID-19?

There is a section on remdesivir in COVID-19 rapid guideline: Managing COVID-19 from the National Institute for Health and Care Excellence (NICE).

Vitamin D supplementation for treating COVID-19

A Cochrane Review on Vitamin D supplementation for the treatment of COVID‐19: a living systematic review (May 2021) has found 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’. The authors conclude that  “There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID‐19”. They identified 21 ongoing studies and three completed studies without published results, so their findings are likely to change when the review is updated. There is a podcast and a Cochrane Clinical Answer with more information.

The impact of the pandemic on other areas of health and wellbeing

Resilience and mental health of frontline healthcare professionals

Working on the ‘front line’ as a health or social care professional during a pandemic is stressful and can negatively impact workers’ mental health. A Cochrane Review on interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic aimed to assess the effects of such interventions and explore things that make it easier or harder to implement them, through both qualitative and qualitative evidence.

Intervention effects remain uncertain. They were explored in just one study. All 16 studies in the review had some limited evidence on things that might help interventions to be successfully delivered. This review highlights a need for robust evaluation of interventions and the review authors suggest that the current pandemic provides unique opportunities for doing so.

Interventions for heavy menstrual bleeding

Pandemics disrupt healthcare provision. With this in mind, a Cochrane overview of reviews (July 2020) has been done on interventions commonly available during pandemics for heavy menstrual bleeding. You can see summaries of the review here, including an infographic to help women make choices about treatment. There is also a podcast about this review and two Cochrane Clinical Answers. 

Routine vaccinations during the pandemic

The World Health Organization (WHO) has emphasized the importance of keeping up with routine vaccinations during the pandemic, advice endorsed by Public Health England. A Cochrane Review on vaccines for measles, mumps, rubella and varicella  in children (published April 2020) was discussed in this blog: “MMR vaccines: do they work and are they safe?“.

Take home points A Cochrane Review has shown that MMR vaccines are effective at preventing measles, mumps, rubella in children.The review found no evidence of an increased risk of autism from MMR vaccination.World Health Organization guidance, supported by Public Health England, advises having routine vaccinations during the COVID 19 pandemic.It is never too late to catch-up on MMR vaccination.

There are two Cochrane Clinical Answers related to this review.

Social isolation and loneliness in older people

With restrictions imposed during the pandemic increasing isolation for many, a Cochrane rapid review (May 2020) looked for evidence on video calls for reducing social isolation and loneliness in older people. We discuss the review in this blog: “Loneliness in older people: could video calls help?

Video calls have the potential to help older people stay connected with others and to reduce loneliness and social isolation. A Cochrane rapid review has highlighted that the evidence on the effects of video calls on loneliness, depression, quality of life and social isolation are very uncertain. It is important to consider an older person’s circumstances as well as their personal preferences for technology such as video calls.

There is also a podcast and a Cochrane Clinical Answer.

Quitting smoking to improve respiratory health

Given the current threat from COVID-19, an acute respiratory infection, there has never been a better time to stop smoking, and the World Health Organization is urging people to do so. We have looked at evidence from a new Cochrane Special Collection, COVID-19: Effective options for quitting smoking during the pandemic, in this blog: “Smoking and coronavirus (COVID-19): time to quit.”

Smoking increases the risk of getting acute respiratory infections and of being more severely affected, as does exposure to second-hand smoke. The Cochrane Special Collection, COVID-19: Effective options for quitting smoking during the pandemic, pulls together evidence including Cochrane Reviews on nicotine replacement, behavioural support such as telephone, internet and text messaging programmes, and gradual quitting. The Cochrane Reviews in the Special Collection focus on interventions that are feasible under public health measures that restrict face to face contact with health practitioners.Preventing and treating persistent symptoms after COVID-19 infection

Preventing and treating persistent symptoms after COVID-19 infection

Persistent problems with sense of smell after COVID-19 infection

A Cochrane Review on Interventions for the prevention of persistent smell disorders (olfactory dysfunction) after COVID‐19 infection and another on Interventions for the treatment of persistent smell disorders after COVID‐19 infection were published in July 2020. They each include only one small study and highlight current uncertainty about how to prevent or treat ongoing problems with sense of smell after COVID-19. However, the review authors found that there are studies being done at the moment and will be able to assess these for inclusion in updates of this ‘living systematic review’, adding new research as it becomes available.

Here’s what they found:

Interventions for the prevention of persistent smell disorders (olfactory dysfunction) after COVID‐19 infection: The potential benefits and harms of interventions to prevent problems with sense of smell (reduced, changed or lost sense of smell) from lasting weeks or months after COVID-19 infection are very uncertain. EVIDENCE GAP. Cochrane Review (published July 2021): one study with 100 people with problems with their sense of smell that started after a COVID-19 infection and had lasted less than four weeks at the start of the study. It compared a steroid spray that goes into the nose with no treatment. Everyone taking part in the study was asked to to spend a short time each day practising smelling particular scents, to try and stimulate their sense of smell to return. This is a living systematic review, which will include new evidence as it becomes available.

Interventions for the treatment of persistent smell disorders (olfactory dysfunction) after COVID‐19 infection: The potential benefits and harms of treatments for problems with sense of smell (reduced, changed or lost sense of smell) that last weeks or months after COVID-19 infection are very uncertain. EVIDENCE GAP. Cochrane Review (published July 2021): one study with 18 people with problems with their sense of smell that started after a COVID-19 infection and lasted at least four weeks. It compared steroid tablets plus a nasal spray (consisting of a mix of steroids, decongestant and an agent that breaks down mucus) with no treatment. This is a living systematic review, which will include new evidence as it becomes available.

Coronavirus (COVID-19): Special Collections

The Special Collection on quitting smoking during the pandemic is one of seven Cochrane Special Collections on COVID-19. Developed with experts from our global Cochrane network, they are based on World Health Organization interim guidance, and continuously updated.

Coming up…

Like the reviews themselves, we update our blogs to reflect the latest evidence. There are new reviews coming up, as well as updates of existing reviews, so check back for additions to this blog.

We also welcomed news (March 2021) of two new clinical trials which have been launched in the UK to investigate potential preventative treatments for the most clinically vulnerable (those with long-term underlying conditions and those in care homes) to prevent them catching COVID-19.

Keeping up to date

As well as coming back to this blog, you can find Cochrane resources and news on COVID-19 and this will also be continually updated.

References (pdf)

Join in the conversation on Twitter with @CochraneUK @SarahChapman30 or leave a comment on the blog. Please note, we will not publish comments that link to commercial sites or appear to endorse commercial products. We welcome diverse views and encourage discussion but ask that comments are respectful and reserve the right to not publish comments we consider offensive.

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

COVID-19 evidence: a Cochrane round-up by Sarah Chapman and Selena Ryan-Vig

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

4 Comments on this post

  1. I can’t find any Cochrane reviews on the efficacy of various covid vaccines. Are there no reviews? Surprises me there isn’t

    Mr noodles / Reply
    • Thank you for this question, which has led us to make enquiries. We understand that a review of the COVID vaccines is being prepared and should be available soon. Meanwhile, you might wish to see the joint Cochrane and WHO COVID-19 living network meta-analysis initiative which provides living maps of evidence on preventing and treating COVID-19 and maintains living syntheses of evidence, including on vaccines, which are updated every 2 weeks.
      The living map of evidence on vaccines is here:
      The living synthesis of RCT evidence on vaccine effectiveness is here:
      The living synthesis of RCT evidence on vaccine effectiveness on variants of concern is here:
      The living synthesis of observational studies evidence on vaccine effectiveness on variants of concern is here:

      The Cochrane protocol for this initiative is here:

      Boutron I, Chaimani A, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Tovey D, Grasselli G, Ravaud P. Interventions for the prevention and treatment of COVID‐19: a living mapping of research and living network meta‐analysis. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD013769. DOI: 10.1002/14651858.CD013769

      We hope this helps.
      Best wishes,
      Sarah Chapman [Editor]

      Sarah Chapman / (in reply to Mr noodles) Reply
  2. I found this blog incredibly useful to present what we have done in Cochrane and why. Thank you very much Sarah!

    Karla Soares-Weiser / Reply
  3. I liked very much those informations!

    Maria Benedita Lima Pardo / Reply

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