First published on 11 February 2020 and updated on an ongoing basis; last updated on 6 August 2024 (changes detailed below); many of the reviews in this Special Collection are free to access.
This Special Collection is one of a series of collections on COVID-19. It is also available in Simplified Chinese, Traditional Chinese, Croatian, Czech, German, Farsi, French, Japanese, Bahasa Malaysia, Polish, Portuguese, Russian, and Spanish.
The aim of this Special Collection is to ensure immediate access to systematic reviews most directly relevant to the management of people hospitalized with severe acute respiratory infections. It includes reviews that are relevant to the WHO interim guidance, and reviews identified as relevant by Cochrane Acute and Emergency Care, informed by Cochrane groups in affected regions.
This Special Collection includes Cochrane Reviews on the following topics: fluid and vasopressor therapy; respiratory support and mechanical ventilation; weaning mechanical ventilation; managing hypoxaemia; pharmacological treatment; managing delirium; nutrition in intensive care; and diagnosis.
While the reviews in this Special Collection assess interventions that are referenced in the WHO interim guidance, the direct applicability of the evidence may be limited by the low proportion of people with viral infection enrolled in the primary studies. Many reviews in the collection have associated Cochrane Clinical Answers.
It is important to note that the reviews included in this Collection summarize evidence; their inclusion does not mean that they are an effective treatment. A number of reviews presented here highlight the paucity of high-quality evidence to inform medical decision-making in the context of a severe acute respiratory infection crisis.
Updated 6 August 2024 with a new Cochrane review, 'Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID-19 in people with SARS-CoV-2'.
Fluid and vasopressor therapy
Initial resuscitation for hypotension typically includes administration of intravenous fluids, followed by initiation of vasopressors when hypotension persists.
Liberal versus conservative fluid therapy in adults and children with sepsis or septic shock
Sepsis and septic shock are potentially life‐threatening complications of infection that are associated with high morbidity and mortality in adults and children. Fluid therapy is regarded as crucial during initial treatment of sepsis, but it is unclear whether conservative or liberal fluid therapy can improve clinical outcomes in patients with sepsis. This review determines whether liberal versus conservative fluid therapy improves clinical outcomes in adults and children with initial sepsis and septic shock. Associated Cochrane Clinical Answer: For children with sepsis or septic shock, how does liberal fluid therapy compare with conservative fluid therapy?
Colloids versus crystalloids for fluid resuscitation in critically ill people
Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are inexpensive, easy to use but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This review assesses the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy, and adverse events. Associated Cochrane Clinical Answer: How do colloids compare with crystalloids for fluid resuscitation in critically ill people?
Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children
Among crystalloid solutions, 0.9% saline is the most commonly administered. Buffered solutions may offer some theoretical advantages (less metabolic acidosis, less electrolyte disturbance), but the clinical relevance of these remains unknown. This review assesses the effects of buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children. Associated Cochrane Clinical Answer: How do buffered solutions compare with 0.9% saline for critically ill people requiring intravenous fluid therapy?
Vasopressors for hypotensive shock
Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient‐relevant outcomes remains controversial. This review aims to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. Associated Cochrane Clinical Answer: How does norepinephrine compare with other vasopressors in people with hypotensive shock?
Respiratory support and mechanical ventilation
Patients with severe acute respiratory infection may require supplemental oxygen and mechanical ventilatory support.
Early versus late tracheostomy in critically ill COVID‐19 patients
Pre‐pandemic evidence on the benefits of early tracheostomy is conflicting but suggests shorter hospital stays and lower mortality rates compared to late tracheostomy. Similarly, the role of early tracheostomy as an intervention for critically ill COVID‐19 patients is unclear. Some reports have described prolonged intensive care stays and difficulty weaning from mechanical ventilation, particularly in those developing acute respiratory distress syndrome. This review sought to assess the benefits and harms of early tracheostomy compared to late tracheostomy in critically ill COVID‐19 patients.
High‐flow nasal cannulae for respiratory support in adult intensive care patients
High‐flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide‐bore nasal cannulae and may be useful in providing respiratory support for adult patients experiencing acute respiratory failure in the intensive care unit (ICU). This review assesses the effectiveness of HFNC compared to standard oxygen therapy, or non‐invasive ventilation or non‐invasive positive pressure ventilation, for respiratory support in adults in the ICU. Associated Cochrane Clinical Answer: For adults in intensive care requiring respiratory support, how does a high‐flow nasal cannula compare with standard oxygen therapy and non‐invasive (positive‐pressure) ventilation (NI[PP]V)?
Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID‐19). This review aims to address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID‐19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life. Associated Cochrane Clinical Answer: For people with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, how do conservative and liberal oxygen targets compare?
Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID‐19Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID‐19, usually resulting in a prolonged stay in an intensive care unit and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID‐19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents. This approach is potentially associated with both advantages as well as risks. As a consequence, spontaneous breathing in people with COVID‐19‐ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. This review aims to assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID‐19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. Associated Cochrane Clinical Answer: In invasively ventilated people with COVID-19 and acute respiratory distress syndrome (ARDS), what are the effects of enabling early spontaneous breathing activity?
Unsuccessful management of the airway is associated with serious morbidity and mortality. The four descriptors of the difficult airway are: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation. Several bedside screening tests are used in clinical practice to identify those at high risk of a difficult airway, although their accuracy and benefit remains unclear. This review characterizes and compares the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. Associated Cochrane Clinical Answers: What is the accuracy of airway physical examination tests for detection of difficult laryngoscopy in adults?; What is the accuracy of the modified Mallampati test for detection of difficult intubation in adults?; and What is the accuracy of airway physical examination tests for detection of difficult face mask ventilation in adults?
Recruitment manoeuvres involve transient elevations in airway pressure applied during mechanical ventilation to open (‘recruit’) collapsed lung units and increase the number of alveoli participating in tidal ventilation. They are often used to treat patients in intensive care who have acute respiratory distress syndrome (ARDS), but the effect of this treatment on clinical outcomes has not been well established. This review aims to determine the effects of recruitment manoeuvres on mortality in adults with acute respiratory distress syndrome as well as the effects of recruitment manoeuvres on oxygenation and adverse events (e.g. rate of barotrauma). Associated Cochrane Clinical Answer: What are the effects of recruitment maneuvers for adults with acute respiratory distress syndrome receiving mechanical ventilation?
Ventilator‐associated pneumonia (VAP) is associated with increased mortality, a prolonged hospital stay, and increased healthcare costs in critically ill patients. Guidelines recommend a semi‐recumbent position (30° to 45°) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi‐recumbent position for preventing VAP. This review assesses the effectiveness and safety of semi‐recumbent positioning versus supine positioning to prevent VAP in adults requiring mechanical ventilation. Associated Cochrane Clinical Answer: How does a semi‐recumbent position compare with a supine position in adults requiring mechanical ventilation?
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) account for one‐quarter of cases of acute respiratory failure in intensive care units (ICUs). Mechanical ventilation of people with ALI/ARDS allows time for the lungs to heal, but ventilation is invasive and can result in lung injury. It is uncertain whether ventilator‐related injury would be reduced if pressure delivered by the ventilator with each breath is controlled, or whether the volume of air delivered by each breath is limited. This review compares pressure‐controlled ventilation versus volume‐controlled ventilation in adults with ALI/ARDS to determine whether pressure‐controlled ventilation reduces in‐hospital mortality and morbidity in intubated and ventilated adults. Associated Cochrane Clinical Answer: How do pressure and volume‐controlled ventilation compare in people with acute respiratory failure or distress syndrome?
Mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation, but this has been associated with ventilator‐induced lung injury. High levels of positive end‐expiratory pressure (PEEP) could reduce this condition and improve patient survival. This review assesses the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS. Associated Cochrane Clinical Answer: How do high and low positive end‐expiratory pressure (PEEP) levels compare for mechanically ventilated adults with acute lung injury and acute respiratory distress syndrome?
Lung protective ventilation strategy for the acute respiratory distress syndrome
Acute respiratory distress syndrome and acute lung injury can be further complicated by ventilator‐induced lung injury. Lung protective ventilation strategies may lead to improved survival. This review assesses the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. It also determines whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. Associated Cochrane Clinical Answer: How does a protective ventilation strategy compare with conventional ventilation for critically ill adults with acute respiratory distress syndrome?
Daily sedation interruption (DSI) is thought to limit drug bioaccumulation, promote a more awake state, and thereby reduce the duration of mechanical ventilation. Available evidence has shown DSI to either reduce, not alter, or prolong the duration of mechanical ventilation. This review aims to compare the total duration of invasive mechanical ventilation for critically ill adult patients requiring intravenous sedation who were managed with DSI versus those with no DSI. And also, to determine whether DSI influenced mortality, intensive care unit (ICU) and hospital lengths of stay, adverse events, the total doses of sedative drug administered, and quality of life. Associated Cochrane Clinical Answer: How does interruption of daily sedation compare with no interruption for critically ill adults requiring invasive mechanical ventilation?
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the strain of coronavirus that causes coronavirus disease 2019 (COVID‐19) can cause serious illness in some people resulting in admission to intensive care units (ICU) and frequently, ventilatory support for acute respiratory failure. Evaluating ICU care, and what is effective in improving outcomes for these patients is critical. Care bundles, a small set of evidence‐based interventions, delivered together consistently, may improve patient outcomes. To identify the extent of the available evidence on the use of care bundles in patients with COVID‐19 in the ICU, the World Health Organization (WHO) commissioned a scoping review to inform WHO guideline discussions. This review aims to identify and describe the available evidence on the use of care bundles in the ICU for patients with COVID‐19 or related conditions (acute respiratory distress syndrome (ARDS) viral pneumonia or pneumonitis), or both. In carrying out the review the focus was on characterising the evidence base and not evaluating the effectiveness or safety of the care bundles or their component parts. Associated Cochrane Clinical Answer: What evidence is available on care bundles for improving outcomes in people with COVID‐19 in the intensive care unit (ICU)?
Weaning mechanical ventilation
Reducing weaning time is desirable in minimizing potential complications from mechanical ventilation.
Methods to improve ventilator weaning processes are needed because prolonged mechanical ventilation is associated with a longer intensive care unit length of stay and higher mortality. Growing awareness of the benefits of understanding the contextual factors impacting on effectiveness has encouraged the integration of qualitative evidence syntheses with effectiveness reviews. This review aimed to investigate the factors influencing how healthcare professionals use protocols to wean adults and children from mechanical ventilation. Associated Cochrane Clinical Answer: What factors affect the use of mechanical ventilation weaning protocols for critically ill people?
Standardized weaning protocols are supposed to reduce time spent on mechanical ventilation. However, evidence supporting their use in clinical practice is inconsistent. This review compares the total duration of mechanical ventilation of critically ill adults who were weaned using protocols versus usual (non‐protocolized) practice. It also determined differences between protocolized and non‐protocolized weaning in outcomes measuring weaning duration, harm (adverse events) and resource use (intensive care unit and hospital length of stay. Associated Cochrane Clinical Answer: How does protocolized compare with non‐protocolized weaning off mechanical ventilation for critically ill adults?
Noninvasive positive‐pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway. Interest has emerged in using NPPV to facilitate earlier removal of an endotracheal tube and to decrease complications associated with prolonged intubation. This review determined whether the NPPV strategy reduced all‐cause mortality compared with invasive positive‐pressure ventilation weaning. It also determined differences between strategies in proportions of weaning failure and ventilator‐associated pneumonia, intensive care unit and hospital length of stay, total duration of mechanical ventilation, duration of mechanical support related to weaning, duration of endotracheal mechanical ventilation, frequency of adverse events (related to weaning) and overall quality of life. Associated Cochrane Clinical Answer: For adults with chronic obstructive pulmonary disease (COPD) and respiratory failure, how do noninvasive and invasive positive‐pressure ventilation (PPV) weaning strategies compare?
Managing hypoxaemia
Acute or chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes.
The mainstay treatment for hypoxaemia is oxygen therapy, which is given to most adults admitted to the intensive care unit. Oxygen administration has been liberal, which may result in hyperoxaemia. Some studies have indicated an association between hyperoxaemia and mortality, whilst other studies have not. Oxygen administration is widely recommended in international clinical practice guidelines, despite a lack of robust evidence. The potential benefit of supplemental oxygen must be weighed against the potentially harmful effects of hyperoxaemia, and this review assesses the benefits and harms of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Associated Cochrane Clinical Answer: For adults admitted to the intensive care unit (ICU), how do different oxygenation levels compare?
Prone position for acute respiratory failure in adults
Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes. This review determines whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation. Associated Cochrane Clinical Answer: How does prone positioning compare with supine positioning for ventilation in adults with severe acute respiratory failure?
Extracorporeal membrane oxygenation for critically ill adults
Extracorporeal membrane oxygenation (ECMO) is a form of life support that targets the heart and lungs, but its use is associated with several risks. ECMO for severe respiratory failure accesses and returns blood from the venous system and provides non‐pulmonary gas exchange. Patient‐related adverse events include haemorrhage or extremity ischaemia; circuit‐related adverse effects may include pump failure, oxygenator failure and thrombus formation. This review aims to determine whether use of veno‐venous or venous‐arterial ECMO in adults is more effective in improving survival compared with conventional respiratory and cardiac support. Associated Cochrane Clinical Answer: What are the effects of extracorporeal membrane oxygenation for critically ill adults with acute respiratory distress syndrome (ARDS)?
Pharmacotherapy
Although fluid resuscitation and ventilatory support are the mainstays of treatment for patients with severe acute respiratory infections requiring acute or critical care, various pharmacological interventions have been suggested, yet the benefits and harms remain uncertain.
Favipiravir for treating COVID‐19
Favipiravir was suggested by some experts to be effective and safe to use in COVID‐19. This review sought to assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID‐19. The review included 25 studies with 5750 participants but the authors' confidence in the evidence was limited. Although this drug has been evaluated in randomized controlled trials, due to a lack of robust evidence it is unclear if favipiravir provides any benefit in the treatment of people with COVID‐19 infections who do not require hospital admission, as well as those admitted to hospital. Favipiravir might lead to mild side effects, but doesn't seem to cause major or severe side effects. it is still unclear if it has a definite role in the treatment of COVID‐19.
Nirmatrelvir combined with ritonavir for preventing and treating COVID‐19
This review aims to assess the effectiveness of nirmatrelvir plus ritonavir (Paxlovid) in reducing deaths, illness, and length of infection in people with mild or asymptomatic COVID-19. First published in September 2020 and updated in November 2023, this review found that oral nirmatrelvir/ritonavir may reduce the risk of all‐cause mortality and hospital admission or death in high‐risk, unvaccinated COVID‐19 outpatients infected with the Delta variant of SARS‐CoV‐2.
Antiplatelet agents for the treatment of adults with COVID‐19
Severe coronavirus disease 2019 (COVID‐19) can cause thrombotic events that lead to severe complications or death. Antiplatelet agents, such as acetylsalicylic acid, have been shown to effectively reduce thrombotic events in other diseases: they could influence the course of COVID‐19 in general. This review aims to assess the efficacy and safety of antiplatelets given with standard care compared to no treatment or standard care (with/without placebo) for adults with COVID‐19.
Fluvoxamine for the treatment of COVID‐19
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive–compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID‐19. As there are only a few effective therapies for people with COVID‐19 in the community, this review examines the efficacy and safety of fluvoxamine as an anti‐inflammatory and possible anti‐viral treatment for COVID‐19. Associated Cochrane Clinical Answer: What are the benefits and harms of fluvoxamine for adults with mild COVID-19?
Interventions for palliative symptom control in COVID‐19 patients
Individuals dying of coronavirus disease 2019 (COVID‐19) may experience distressing symptoms such as breathlessness or delirium. Palliative symptom management can alleviate symptoms and improve the quality of life of patients. Various treatment options such as opioids or breathing techniques have been discussed for use in COVID‐19 patients. However, guidance on symptom management of COVID‐19 patients in palliative care has often been derived from clinical experiences and guidelines for the treatment of patients with other illnesses. This review assesses the efficacy and safety of pharmacological and non‐pharmacological interventions for palliative symptom control in individuals with COVID‐19. Associated Cochrane Clinical Answer: For people with COVID‐19 and terminal disease, what are the effects of pharmacological interventions for palliative symptom control?
Systemic corticosteroids are used to treat people with COVID‐19 because they counter hyper‐inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID‐19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated. This review aims to assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID‐19 and to keep up to date with the evolving evidence base using a living systematic review approach. Associated Cochrane Clinical Answer: For adults hospitalized with acute or suspected COVID‐19, what are the benefits and harms of systemic corticosteroids?
Inhaled corticosteroids for the treatment of COVID-19
Inhaled corticosteroids are well established for the long‐term treatment of inflammatory respiratory diseases such as asthma or chronic obstructive pulmonary disease, and they have been investigated for the treatment of COVID‐19. The anti‐inflammatory action of inhaled corticosteroids might have the potential to reduce the risk of severe illness resulting from hyperinflammation in COVID‐19. This review assesses whether inhaled corticosteroids are effective and safe in the treatment of COVID‐19, using a living systematic review approach to maintain the currency of the evidence. Associated Cochrane Clinical Answer: For people with mild COVID-19, what are the effects of inhaled corticosteroids?
Risk of thromboembolism in patients with COVID‐19 who are using hormonal contraception
Hormonal contraception is a common medication, however, its use is a risk factor for thrombosis. People with COVID-19 are also at risk of thrombotic events, but it is unclear if hormonal contraception use among COVID‐19-positive women increases or attenuates risk of thromboembolism - higher estrogen levels may be protective against severe COVID‐19 disease. Evidence for risks of hormonal contraception use during the COVID‐19 pandemic is sparse. This review aims to determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID‐19, and whether its use increases other markers of COVID‐19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. This is a living systematic review. It is likely that the conclusions of this review, including estimates of effect, will change as new evidence is generated. Associated Cochrane Clinical Answer: Does hormonal contraception increase the risk of thromboembolism in women with COVID‐19?
Ivermectin for preventing and treating COVID‐19
Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS‐CoV‐2 infection and COVID‐19 treatment is conflicting. This review aims to assess the efficacy and safety of ivermectin plus standard of care compared to standard of care plus/minus placebo, or any other proven intervention for people with COVID‐19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS‐CoV‐2 (postexposure prophylaxis). Associated Cochrane Clinical Answer: For adults with mild or moderate to severe symptomatic COVID-19, what are the effects of ivermectin?
Remdesivir for the treatment of COVID‐19
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS‐CoV‐2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID‐19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS‐CoV‐2 infection based on randomised controlled trials (RCTs) is required. This review aims to assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS‐CoV‐2 infection. Associated Cochrane Clinical Answers: What are the effects of remdesivir for treating moderate to severe COVID-19? and For people with asymptomatic SARS-CoV-2 infection or mild COVID-19, what are the benefits and harms of remdesivir?
Colchicine for the treatment of COVID‐19
The development of severe COVID‐19 and poor clinical outcomes are associated with hyperinflammation and a complex dysregulation of the immune response. Colchicine is an anti‐inflammatory medicine and is thought to improve disease outcomes in COVID‐19 through a wide range of anti‐inflammatory mechanisms. Patients and healthcare systems need more and better treatment options for COVID‐19 and a thorough understanding of the current body of evidence. This review assess the effectiveness and safety of colchicine as a treatment option for COVID‐19 in comparison to an active comparator, placebo, or standard care alone in any setting, and to maintain the currency of the evidence, using a living systematic review approach. Associated Cochrane Clinical Answers: What are the effects of colchicine for treatment of moderate to severe COVID-19? and What are the effects of colchicine for treatment of asymptomatic or mild COVID-19?
Janus kinase inhibitors for the treatment of COVID‐19
With potential antiviral and anti‐inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic SARS‐CoV‐2 infection. They may modulate the exuberant immune response to SARS‐CoV‐2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID‐19) is required. This review assessed the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in‐hospital) with any severity of COVID‐19, and to maintain the currency of the evidence using a living systematic review approach. Associated Cochrane Clinical Answer: What are the effects of janus kinase (JAK) inhibitors for people with moderate to severe COVID‐19?
SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19
Monoclonal antibodies (mAbs) are laboratory‐produced molecules derived from the B cells of an infected host, designed to target only one specific protein. They have been used successfully to treat other viruses and are being investigated as a potential therapy for coronavirus disease 2019 (COVID‐19). This review assesses the effectiveness and safety of SARS‐CoV‐2‐neutralising mAbs for treating patients with COVID‐19, compared to an active comparator, placebo, or no intervention, and uses a living systematic review approach to maintain the currency of the evidence. Associated Cochrane Clinical Answers: For adults hospitalized with moderate to severe COVID-19, what are the effects of SARS-CoV-2-neutralising monoclonal antibodies (alone or combined)? and For adults with asymptomatic or mild COVID-19, what are the efects of SARS-CoV-2-neutralising monoclonal antibodies (alone or combined)?
Vitamin D supplementation for the treatment of COVID‐19: a living systematic review
The role of vitamin D supplementation as a treatment for COVID‐19 has been a subject of considerable discussion. Some studies have shown that people who are in hospital with severe COVID‐19 also have low levels of vitamin D. However, the risk factors for developing severe COVID‐19 are the same as those for developing vitamin D deficiency, so it is difficult to tell if vitamin D deficiency itself is a risk factor for severe COVID‐19. This review assesses whether vitamin D supplementation is effective and safe for the treatment of COVID‐19 in comparison to an active comparator, placebo, or standard of care alone, and uses a living systematic review approach to maintain the currency of the evidence. Associated Cochrane Clinical Answer: For people with moderate to severe COVID-19, what are the benefits and harms of vitamin D supplementation?
Interleukin‐6 blocking agents for treating COVID‐19: a living systematic review
Interleukin 6 (IL‐6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID‐19). Their immunosuppressive effect might be valuable in patients with COVID‐19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance. This review assesses the effect of IL‐6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID‐19. Associated Cochrane Clinical Answer: For adults with COVID‐19, what are the effects of the interleukin‐6 blocking agents tocilizumab and sarilumab?
Interleukin‐1 blocking agents for treating COVID‐19
Interleukin‐1 (IL‐1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID‐19), on the premise that their immunomodulatory effect might be beneficial in people with COVID‐19. This review assesses the effects of IL‐1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID‐19. Associated Cochrane Clinical Answer: For people with moderate, severe or critical COVID-19 illness, what are the effects of interleukin 1 (IL-1) blocking agents (anakinra or canakinumab)?
Chloroquine or hydroxychloroquine for prevention and treatment of COVID‐19
The coronavirus disease 2019 (COVID‐19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. This review aims to evaluate the effects of CQ or HCQ for treating people with COVID‐19 on death and time to clearance of the virus; preventing infection in people at risk of SARS‐CoV‐2 exposure; and preventing infection in people exposed to SARS‐CoV‐2. Associated Cochrane Clinical Answer: For adults with coronavirus disease 2019 (COVID‐19), what are the benefits and harms of hydroxychloroquine?
Pharmacological agents for adults with acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is a life‐threatening condition caused by direct or indirect injury to the lungs. This review evaluates the effectiveness of pharmacological agents in adults with ARDS on mortality, mechanical ventilation, and fitness to return to work at 12 months. Associated Cochrane Clinical Answer: What are the effects of pharmacological agents for adults with acute respiratory distress syndrome (ARDS)?
Anticoagulants for people hospitalised with COVID‐19
The primary manifestation of COVID-19 is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and thromboembolic events, such as pulmonary embolism, deep vein thrombosis, or arterial thrombosis. People with COVID‐19 who develop thromboembolism have a worse prognosis. Anticoagulants such as heparinoids (heparins or pentasaccharides), vitamin K antagonists and direct anticoagulants are used for the prevention and treatment of venous or arterial thromboembolism. Besides their anticoagulant properties, heparinoids have an additional anti‐inflammatory potential. However, the benefit of anticoagulants for people with COVID‐19 is still under debate. This review aims to assess the effects of prophylactic anticoagulants versus active comparator, placebo or no intervention, on mortality and the need for respiratory support in people hospitalised with COVID‐19. Associated Cochrane Clinical Answer: How do higher-dose anticoagulants compare with lower-dose for people with moderate to severe COVID-19?
Convalescent plasma for people with COVID‐19: a living systematic review
Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID‐19). This review aims to assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID‐19.
Hyperimmune immunoglobulin for people with COVID‐19
Hyperimmune immunoglobulin contains polyclonal antibodies, which can be prepared from large amounts of pooled convalescent plasma or prepared from animal sources through immunisation. They are being investigated as a potential therapy for COVID‐19. This review was previously part of a parent review addressing both convalescent plasma and hyperimmune immunoglobulin and was split to address hIVIG and convalescent plasma separately. This living systematic review aims to assess the benefits and harms of hyperimmune immunoglobulin therapy for the treatment of people with COVID‐19. Associated Cochrane Clinical Answers: What are the benefits and harms of hyperimmune immunoglobulin (hIVIG) from human plasma for treating adults with moderate/severe COVID‐19? and For adults with moderate/severe COVID‐19, what are the effects of hyperimmune immunoglobulin, specifically equine polyclonal antibodies (EpAbs)?
Immunonutrition for acute respiratory distress syndrome (ARDS) in adults
Acute respiratory distress syndrome (ARDS) is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Pharmacotherapies that moderate inflammation in ARDS are lacking. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. This review critically appraises available evidence on the effects of immunonutrition compared to standard non‐immunonutrition formula feeding on mechanically ventilated adults with ARDS. Associated Cochrane Clinical Answer: For adults with acute respiratory distress syndrome (ARDS) who are mechanically ventilated, how does immunonutrition compare with standard formula feeding?
Antibiotics for the treatment of COVID‐19
The effect of antibiotics with potential antiviral and anti‐inflammatory properties are being investigated in clinical trials as treatment for COVID‐19. The use of antibiotics follows the intention‐to‐treat the viral disease and not primarily to treat bacterial co‐infections of individuals with COVID‐19. A thorough understanding of the current evidence regarding effectiveness and safety of antibiotics as antiviral treatments for COVID‐19 based on randomised controlled trials (RCTs) is required. This review assesses the efficacy and safety of antibiotics compared to each other, no treatment, standard of care alone, placebo, or any other active intervention with proven efficacy for treatment of COVID‐19 outpatients and inpatients. Associated Cochrane Clinical Answers: For adults with asymptomatic or mild COVID‐19, what are the effects of azithromycin? and For adults hospitalized with moderate to severe COVID‐19, what are the effects of azithromycin?
Pneumonia is the most common hospital‐acquired infection affecting patients in the intensive care unit. However, current national guidelines for the treatment of hospital‐acquired pneumonia (HAP) are several years old and the diagnosis of pneumonia in mechanically ventilated patients (VAP) has been subject to considerable recent attention. The optimal duration of antibiotic therapy for HAP in the critically ill is uncertain. This review assesses the effectiveness of short versus prolonged‐course antibiotics for HAP in critically ill adults, including patients with VAP. Associated Cochrane Clinical Answer: Which regimen is most effective at improving outcomes in critically ill adults with hospital‐acquired pneumonia: short‐course or prolonged‐course antibiotic therapy?
Antibiotics for community‐acquired pneumonia in children
Pneumonia caused by bacterial pathogens is the leading cause of mortality in children in low‐income countries. Early administration of antibiotics improves outcomes. This review aims to identify effective antibiotic drug therapies for community‐acquired pneumonia of varying severity in children by comparing various antibiotics. Associated Cochrane Clinical Answers: In children admitted to hospital with community‐acquired pneumonia, how do different antibiotics compare with each other? And In children with community‐acquired pneumonia in the ambulatory setting, what are the effects of oral antibiotics?
Community‐acquired pneumonia (CAP) is caused by various pathogens, traditionally divided into 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. This review aims to estimate the mortality and proportion with treatment failure using regimens containing atypical antibiotic coverage, compared with those that had typical coverage only. Associated Cochrane Clinical Answer: In hospitalized adults with community‐acquired pneumonia, is there randomized controlled trial evidence to support the use of empiric atypical antibiotic coverage over typical antibiotic coverage?
Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS)
Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by a novel coronavirus, which first appeared in Foshan City, China on 22 December 2002. Chinese herbs were used in its treatment. This review evaluates the possible effectiveness and safety of Chinese herbs, combined with Western medicines versus Western medicines alone for SARS patients. Associated Cochrane Clinical Answer: What are the benefits and harms of Chinese herbs combined with Western medicine for people with severe acute respiratory syndrome (SARS)?
Managing delirium
Delirium is defined as a disturbance in attention, awareness, and cognition, with reduced ability to direct, focus, sustain, and shift attention, and reduced orientation to the environment.
Pharmacological interventions for the treatment of delirium in critically ill adults
Delirium is typically an acute reversible cognitive impairment, and its presence is associated with devastating impact on both short‐term and long‐term outcomes for critically ill patients. Considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population. This review assesses the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of delirium. Associated Cochrane Clinical Answer: What are the benefits and harms of pharmacological interventions for treating critically ill adults with delirium?
Interventions for preventing intensive care unit delirium in adults
Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay, and long‐term cognitive impairment. This review assesses existing evidence for the effect of preventive interventions on ICU delirium, in‐hospital mortality, the number of delirium‐ and coma‐free days, ventilator‐free days, length of stay in the ICU and cognitive impairment. Associated Cochrane Clinical Answer: How does haloperidol compare with placebo for preventing delirium in critically ill adults in intensive care?
Nutrition in intensive care
Critically ill people are at increased risk of malnutrition. Acute and chronic illness, trauma and inflammation induce stress‐related catabolism, and drug‐induced adverse effects may reduce appetite or increase nausea and vomiting. In addition, patient management in the intensive care unit (ICU) may also interrupt feeding routines.
Methods to deliver nutritional requirements include provision of enteral nutrition (EN), or parenteral nutrition (PN), or a combination of both. However, each method is problematic. This review aims to determine the route of delivery that optimizes uptake of nutrition. It compares the effects of EN versus PN, and the effects of EN versus a combination of EN and PN among critically ill adults, in terms of mortality, number of ICU‐free days, and adverse events. Associated Cochrane Clinical Answer: How does enteral nutrition compare with parenteral nutrition (with or without enteral nutrition) for adults admitted to the intensive care unit (ICU)?
Diagnosis
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus and resulting COVID‐19 pandemic present important diagnostic challenges.
Obesity as an independent risk factor for COVID‐19 severity and mortality
People with a very high BMI (> 40 kg/m2) may be at higher risk of adverse outcomes from COVID-19 than those with a low BMI. This review aimed to evaluate the effect of very high BMI on mortality, need for mechanical ventilation, hospitalisation, admission to intensive care, severe disease or pneumonia in adults with confirmed COVID-19 disease. Associated Cochrane Clinical Answer: For adults with COVID-19, does obesity affect outcomes?
COVID‐19 and its cardiovascular effects: a systematic review of prevalence studies
A small minority of people with coronavirus disease 2019 (COVID‐19) develop a severe illness, characterised by inflammation, microvascular damage and coagulopathy, potentially leading to myocardial injury, venous thromboembolism and arterial occlusive events. People with risk factors for or pre‐existing cardiovascular disease may be at greater risk. This review assesses the prevalence of pre‐existing cardiovascular comorbidities associated with suspected or confirmed cases of COVID‐19 in a variety of settings, including the community, care homes and hospitals. It also assesses the nature and rate of subsequent cardiovascular complications and clinical events in people with suspected or confirmed COVID‐19. Associated Cochrane Clinical Answer: What are the cardiovascular effects of COVID‐19?
Antibody tests for identification of current and past infection with SARS‐CoV‐2
This updated review summarises evidence of the accuracy of COVID‐19 antibody tests; both laboratory‐based tests and rapid tests using a lateral flow format. The diagnostic challenges associated with the COVID‐19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS‐CoV‐2 infection. Serology tests to detect the presence of antibodies to SARS‐CoV‐2 enable detection of past infection and may detect cases of SARS‐CoV‐2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS‐CoV‐2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS‐CoV‐2 epidemiology. Associated Cochrane Clinical Answer: What is the accuracy of immunoglobulin G (IgG) and IgM antibody tests for the detection of current SARS‐CoV‐2 infection? and What is the accuracy of immunoglobulin G (IgG) and IgM antibody tests for the detection of past SARS‐CoV‐2 infection?
COVID‐19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life‐threatening consequences. Symptoms such as fever, cough, or loss of sense of smell (anosmia) or taste (ageusia), can help flag early on if the disease is present. Such information could be used either to rule out COVID‐19 disease, or to identify people who need to go for COVID‐19 diagnostic tests. This review, updated twice since its first publication in 2020, assesses the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID‐19 clinics, has COVID‐19. Associated Cochrane Clinical Answer: What is the accuracy of World Health Organization (WHO)‐specified and related COVID‐19 symptoms for the diagnosis of COVID‐19?
Thoracic imaging tests for the diagnosis of COVID‐19
The diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) presents major challenges. Reverse transcriptase polymerase chain reaction (RT‐PCR) testing is used to diagnose a current infection, but its utility as a reference standard is constrained by sampling errors, limited sensitivity (71% to 98%), and dependence on the timing of specimen collection. Chest imaging tests are being used in the diagnosis of COVID‐19 disease, or when RT‐PCR testing is unavailable. This review determines the diagnostic accuracy of chest imaging (computed tomography (CT), X‐ray and ultrasound) in people with suspected or confirmed COVID‐19. Associated Cochrane Clinical Answer: What is the accuracy of chest computed tomography (CT) and chest X‐ray for the diagnosis of COVID‐19?
Routine laboratory testing to determine if a patient has COVID‐19
Specific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and resulting COVID‐19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C‐reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID‐19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited. This review aims to assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID‐19. Associated Cochrane Clinical Answer: What is the accuracy of changes in white blood cell (WBC) count for diagnosing COVID‐19?
It is important to identify people with COVID-19 disease whose condition may deteriorate, to assess whether they should receive intensive care or whether they can be treated in a less intensive way or through outpatient care. This review assesses the effectiveness of routine, blood-based laboratory tests in someone with diagnosed SARS-CoV-2 infection and with moderate or mild COVID-19 to predict their likelihood of death or deterioraton to severe or critical COVID-19.
Acknowledgements
This Special Collection was developed by Michael Brown (Senior Editor, Cochrane Acute and Emergency Care; Senior Editor, Cochrane Circulation and Breathing) and Harald Herkner (Co-ordinating Editor, Cochrane Emergency and Critical Care), working with Toby Lasserson (Deputy Editor in Chief), Liz Bickerdike (Associate Editor), Robin Featherstone (Information Specialist), and Monaz Mehta (Editor) in the Cochrane Editorial Methods Department.
Translation
This Special Collection was translated into [language] by [name of Cochrane Group and optionally translators] on [date of the latest translation update].
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Contact
Cochrane Editorial and Methods Department (emd@cochrane.org)