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Evidence Check - Symptoms and treatment

Asymptomatic, disease progression, ambulance, drugs, community, hospitalisation, recovery, palliative care, death.

Ivermectin and COVID-19

Added: 23 Dec 2020
Updated: 15 Jan 2021

Ivermectin and COVID-19
  • Currently, there are insufficient data to support the use of ivermectin for prophylaxis or treatment of COVID-19. - There was insufficient evidence to include ivermectin in the 17 December 2020 release of the BMJ living systematic review on drug treatments
  • however, three randomised controlled trials will be included in the next update inclusion. - The 17 December 2020 update for the World Health Organization guideline on drugs for COVID-19 does not include ivermectin.
  • While there is evidence of in vitro activity of ivermectin on infected cells, the necessary concentrations for in vivo effect are unlikely to be attainable in humans.
  • The Pan American Health Organisation, the World Health Organization regional office for the Americas, published a report in June 2020 that stated studies on ivermectin were found to have a high risk of bias, very low certainty of the evidence, and that the existing evidence is insufficient to draw a conclusion on benefits and harm.
  • While a more recent systematic review found a statistically significant effect on mortality and symptoms, the quality of evidence was very low.
  • There is continuing interest particularly in the Americas, India, and Bangladesh in the use of ivermectin prophylactically and therapeutically.
  • Emerging evidence from randomised controlled trials is mixed. - High dose ivermectin showed no reduction in viral load at day five. - Patients receiving ivermectin plus standard care reported improvement in laboratory and severity parameters. - A phase 2 clinical trial showed a decrease in hospitalisation and duration of low oxygen saturation with adjunct ivermectin treatment. - A three-arm randomised controlled trial of a five-day course of ivermectin reported that changes in patient symptoms were not clinically significant compared with placebo.
  • In the USA, the Front Line COVID-19 Critical Care Alliance advocates for further study of ivermectin. However, the US Food and Drug Administration released advice on 16 December 2020 that ivermectin is not approved for the prevention or treatment of COVID-19.

Aged care facilities and COVID-19

Added: 10 Dec 2020

What are different jurisdictions doing to manage COVID-19 in aged care facilities?
What evidence is there about best practice in preventing and managing COVID-19 infections?
  • More than 71,000 people live in residential aged care facilities in NSW and to date, there have been 61 COVID-19 cases in these facilities and 29 deaths. Incidence is low in comparison with most other jurisdictions.
  • Of the total 52 COVID-19 deaths in NSW, 56% (n=29) occurred in residential aged care facilities. Available international comparisons on this indicator range from 0% in Hong Kong to 82% in Canada.
  • An international review identified emerging evidence on measures to contain COVID-19 outbreaks in care homes. - Early detection and rapid response after detection of index case - Systematic testing of all residents and staff (due to the high prevalence of asymptomatic and pre-symptomatic cases that would not be detected by symptom screening or one-off testing) - Moving high-risk contacts of cases out of the facility - Isolating cases by removing them from the facility or creating separate wards within the facility.
  • A systematic review and expert consensus from the European Geriatric Medicine Society advocates for universal adoption of standards of medical care in nursing homes.
  • Digital technologies have shown some promise in aged care facilities for contact tracing and early identification and remote monitoring.
  • Case studies report effective collaborations between a hospital and nursing homes in Canada and the US and a three phase system response (initial, delayed, surge) in Washington State.
  • A number of studies, predominantly from the US, found an association between COVID-19 incidence and staffing levels and ratios.
  • In North American studies, the odds of a COVID-19 outbreak was associated with the incidence of disease in the region surrounding a facility, the number of residents, older design standards of the home, and the proportion of African American residents, but not profit status.

Medium- and long-term health sequelae of COVID-19 evidence check

Added: 26 Aug 2020

What are the medium- and long-term health sequelae of COVID-19 infection among survivors?
  • Symptoms commonly reported among recovered COVID-19 patients two to eight weeks after the onset of symptoms (or a positive COVID-19 test) include: fatigue, shortness of breath, muscle or joint pain, chest pain, cough, and insomnia and/or sleep disorders.(1-6)
  • A study of 202 confirmed COVID-19 patients with mild symptoms, found altered sense of smell or taste occurred in 18.6% of patients, feelings of being tired in 13.1%, problems breathing in 10.4% and muscle or joint pains in 7.7%.(2) Another study of 143 patients reported fatigue in 53.1%, dyspnea in 43.4%, joint pain in 27.3%, and chest pain 21.7% of patients.(1)
  • A study conducted among discharged intensive care unit (ICU) and ward COVID-19 patients found that post-traumatic stress disorder, anxiety and/or depression, voice change, laryngeal sensitivity, new continence problems and dysphagia were commonly reported among recovered patients.(5)

Vascular dysfunction and COVID-19 evidence check

Added: 5 Aug 2020

What are the symptoms and incidence for vascular events in patients with COVID-19?
  • Thrombotic vasculopathy - A systematic review of 11 studies including 1,765 COVID-19 positive patients reported the occurrence of venous thromboembolism (VTE) in approximately 20% of patients.
  • Cerebrovascular manifestations - A systematic review has reported occurrence of stroke in 3.5% of patients based on a pooled analysis of five studies including 973 patients. Many patients with cerebrovascular complications have cerebrovascular risk factors, such as hypertension, diabetes mellitus, hyperlipidaemia, high BMI, smoking or previous stroke history.
  • Systemic vasculitis - An association between COVID-19 infection and novel paediatric vasculitis, named later as multisystem inflammatory syndrome in children (MIS-C) has not yet been established, due to inconsistent testing of COVID-19, although it seems plausible, given the temporal association. In adults, the spectrum of complications following COVID-19 is broader than in children and includes autoimmune diseases, but their incidence is low. Case reports describe a wide range of clinical presentations of COVID-19 related to systemic vasculitis including cutaneous manifestations, and possible vascular involvement in remote tissues.
  • Neurovascular involvement - In a retrospective study of 214 patients with COVID-19, neurologic symptoms were seen in 36% of patients and were more common in patients with severe infection. Apart from cerebrovascular disease and impaired consciousness, most neurologic manifestations occurred early in the illness. Involvement of vascular endothelium in hyperinflammatory pro-thrombotic state has been proposed as a possible mechanism for neurologic manifestations in patients with severe COVID-19.

Risks associated with surgery in people with COVID-19 evidence check

Added: 20 Jul 2020

Are patients with COVID-19 or who have previously had COVID-19 at risk of adverse post-operative outcomes? If so, what is the duration of the heightened risk?
  • There were no studies reporting empirical data on recovered COVID-19 patients undergoing surgery. One study reported recommendations without data, advising to follow the precautionary principle and undertake the same precautions in the operating room as for a confirmed patient.
  • The main surgical outcomes reported in literature for COVID-19 patients were clinical complications from surgery (e.g. pulmonary, thrombotic), including COVID-19 specific ICU admission requiring post-operative supplemental oxygenation, the impact on length of hospital stay and death (i.e. 30 day mortality)
  • Studies have reported the risk factors that are associated with adverse surgical outcomes in COVID-19 patients undergoing surgery which include, age (e.g. being 70 years or older), being male, positive smoking status, presence of multi- and co-morbidities, having cancer surgery, needing emergency surgery and needing major surgery.
  • Researchers from the COVIDSurg Collaborative conducted an international, multicentre, cohort at 235 hospitals in 24 countries, which included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The analysis included 1,128 patients, who had surgery between January and March 2020. The authors found that post-operative pulmonary complications occurred in half of the patients with perioperative SARS-CoV-2 infection (577 of 1128, 51.2%). The infection was also associated with high mortality, with the 30 day mortality of 38.0% (219 of 577) in these patients, accounting for 81.7% (219 of 268) of all deaths.
  • Based on their findings, authors from the studies included in this evidence check advise the following: Testing and appropriate diagnosis of all patients before surgical treatment to determine COVID-19 status, especially as it is difficult to distinguish between non-COVID-19, asymptomatic, or pre-symptomatic cases. To balance the increased risks associated with SARS-CoV-2 infection against the risks of delaying surgery in individual patients. Rapid evidence checks are based on a simplified review method and may not be entirely exhaustive, but aim to provide a balanced assessment of what is already known about a specific problem or issue. This brief has not been peer-reviewed and should not be a substitute for individual clinical judgement, nor is it an endorsed position of NSW Health. COVID-19 Critical Intelligence Unit 20 July 2020 To consider postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery in COVID-19 patients. This is recommended especially for those with increased vulnerability for adverse outcomes, including elderly patients and those with comorbidities, and in various types of surgeries and procedures, including: adjuvant chemotherapy or elective surgery for stable cancer thoracic operations urological surgery orthopaedic surgery neurosurgery.
  • Only one study reported that patients with asymptomatic or mild COVID-19 infection can safely undergo early surgical intervention for hip fracture after appropriate medical optimisation.

Computed tomography use during the COVID-19 pandemic evidence check

Added: 4 Jun 2020

What is evidence for the use of computed tomography (CT) in patients with COVID-19?
2. What alternative imaging/diagnostics are being used if CT is not recommended?
  • Articles published early in the pandemic described the use of CT as a primary or adjunct technique for diagnosing COVID-19. More recently, practice has moved away from the use of CT for primary diagnosis due to poor utility and safety concerns.
  • Practice varies in the use of CT on patients with COVID-19. According to five large systematic reviews, CT has been used to identify various lung complications, including round-glass opacity, bilateral compromise, unilateral compromise, peripheral distribution, multilobular involvement and consolidation.
  • There are no comparative diagnostic imaging studies, no comparative effectiveness research, nor health technology assessments comparing CT with another technique for diagnosing COVID-19.

Large vessel occlusion strokes in COVID-19 patients evidence check

Added: 27 May 2020

Large vessel occlusion stroke in COVID-19
  • Small series of stroke in COVID-19 patients have been reported: o A letter in the New England Journal of Medicine (NEJM) featured five COVID-19 positive cases of new-onset symptoms of large-vessel stroke in patients younger than 50 years of age, who presented to a New York health system over a two-week period. o A letter in the British Medical Journal (BMJ) describes six consecutive cases of acute ischaemic stroke and COVID-19, all of which had large-vessel occlusion (LVO). o An article published in Brain, Behaviour and Immunity identified four patients with acute stroke and COVID-19 in New York, including two with LVO.
  • Other case series have reported acute ischaemic stroke in patients with COVID-19 suggesting neurological manifestation of COVID-19. In two of these cases, patients had severe COVID-19 infections.
  • A single case report of administration of intravenous rt-PA to an ischemic stroke COVID-19 positive patient has been published, with no bleeding reported.
  • Other than this case report, there are no studies in stroke patients with COVID-19 looking at outcomes post alteplase treatment.
  • Guidance for stroke patients with COVID-19 state that despite the concern of impaired recombinant tissue plasminogen activator (rt-PA) hepatic clearance, no data are available to suggest a greater risk or benefit with intravenous rt-PA.

Renal replacement therapies for COVID-19 positive patients in ICU evidence check

Added: 12 May 2020
Updated: 20 May 2020

What is the current evidence on the use of renal replacement therapies in intensive care units for patients with COVID-19?
  • COVID-19 most frequently presents as mild respiratory illness and can generally be managed outside the hospital. About 20% of patients require hospitalisation, and of those, a quarter require intensive care.
  • ICU patients typically require management of hypoxaemic respiratory failure or hypotension requiring vasopressor support. Acute kidney injury is a less common complication but is associated with a significant risk for mortality.
  • Available data suggests that the prevalence of acute kidney injury in COVID-19 patients is around 3-9% and is more common in patients with severe disease, reported in up to 30% of critically ill or deceased patients.

Daily Evidence Digest

Rapid evidence checks are based on a simplified review method and may not be entirely exhaustive, but aim to provide a balanced assessment of what is already known about a specific problem or issue. This brief has not been peer-reviewed and should not be a substitute for individual clinical judgement, nor is it an endorsed position of NSW Health.