Evidence Check - Symptoms, diagnosis and treatment
Asymptomatic, disease progression, ambulance, drugs, community, hospitalisation, recovery, palliative care, death.
COVID-19 and maternity and newborn communities of practice
Added: 2 Jul 2021
What is the current evidence for vaccinating breastfeeding and pregnant women and women who are on oral contraceptive pill?
What are the current recommendations for infection control measures for group sessions in an indoor setting?
- There is no clear evidence of vertical transmission of SARS-CoV-2. In COVID-19 positive neonates born to infected individuals, it is challenging to determine if the transmission occurred in utero, intrapartum or postpartum due to lack of standardised international definition and classification system for timing, diagnostic testing limitations, such as lack of timely collection of appropriate specimens and method specificity and sensitivity.
- A population-based cohort study from the United Kingdom estimated the neonatal incidence of SARS-CoV-2 infection to be 5-6 (95% confidence interval 4·3-7·1) per 10,000 live births. In an overview of systematic reviews of outcomes of COVID-19 positive mothers, the neonatal polymerase chain reaction positivity rates range between 1.6% and 10%. There were reports of neonates with serum antibody positivity yet negative polymerase chain reaction (PCR) positivity. There is no clear evidence of SARS-CoV-2 transmission to neonates via breastmilk.
- Around 20% of neonates with SARS-CoV-2 infection are asymptomatic and further 40%-50% have mild symptoms. Reported symptoms include rhinorrhoea, cough, lethargy, vomiting, diarrhoea, apnea, fever, tachycardia, tachypnea, leucocytosis, thrombocytopenia, hypoxemia, hypotension, raised C-reactive protein, elevated lactate and radiographic findings of ground-glass opacities. Early onset of neonatal COVID-19 infection (between two and seven days after birth) is likely, however, the majority of symptomatic infections are late-onset (after 7 days of birth).
COVID-19 rapid testing
Added: 19 Apr 2021
- Different types of rapid COVID-19 tests are available: - Antigen tests – identify constituent proteins of the virus, - Molecular tests – detect the viral RNA (often referred to as nucleic acid tests), - Antibody tests – detect SARS-CoV-2-specific antibodies produced after a person is infected.
- This evidence check is focused on molecular and antigen tests which are used to diagnose current infection with SARS-CoV-2.
- Nucleic Acid Tests include reverse transcription-polymerase chain reaction (RT-PCR) which are considered the standard method for diagnosing COVID-19 disease
- complemented by clinical and radiological features. There are very few true ‘point-of-care’ nucleic acid tests, but there are rapid nucleic acid tests.
- RT-PCR typically uses upper or lower respiratory tract specimens and takes up to six hours in a specialised laboratory
- rapid nucleic acid testing (NAT) can provide results in approximately one hour. Turnaround times are impacted by the time required for a sample to be delivered to the laboratory and preanalytical data entry.
- Point-of-care antigen tests (not nucleic acid testing) provide results within minutes of the test being administered, facilitating rapid decisions about patient care. These tests can also extend testing to communities and populations that cannot readily access laboratory facilities.
- Multiple manufacturers have produced rapid tests (Appendix 1). Most are specific to a specimen type, for example nasopharyngeal swab or saliva. The literature indicates differences in sensitivity and specificity across different products and reported results from independent evaluations tend to be lower than manufacturers’ claims.
- A Cochrane systematic review of 22 studies of antigen and molecular tests concluded the evidence is not strong enough to determine how useful the tests are in clinical practice. Head-to-head comparisons are limited.
- For antigen tests, most studies report low sensitivity and recommend against this type of test for COVID-19 diagnosis.
- A variation on antigen tests which detect within finger prick blood samples host response proteins, Myxovirus resistance protein A (MxA) (a marker of interferon-induced antiviral host response) and C reactive protein (CRP), have shown some promise. However, they are non-specific to COVID-19 and have limited value in comparison to nucleic acid testing.
- For molecular tests, the results are mixed with some products found to be of comparable sensitivity and specificity to the standard nucleic acid tests Xpert Xpress, COVIDNudge, NeuMoDx, SAMBA and RT-LAMP.
- Less sensitive rapid antigen tests may have improved sensitivity if done frequently.
Post-acute sequelae SARSCoV2
Added: 1 Apr 2021
- Post-infection syndromes, often with fatigue as a major symptom, are well described. They are most commonly associated with viral infections and were a feature of SARS.
- For some COVID-19 survivors, symptoms occur beyond the acute phase of illness, either with typical signs and symptoms that extend for far longer than usual, or with post-acute disease sequelae that manifest after resolution of the initial illness.
- The terms long COVID and long-haulers are frequently used for this group and while evocative, they are imprecise terms and are not recognised as diagnostic or scientific terminology.(1, 2)
- Imprecision in the terms related to persistent illness has resulted in broad prevalence estimates ranging from 13% to 87% of all acute infections.(3)
- The term post-acute sequelae or PASC of SARS-CoV-2 infection was introduced in January 2021by the US National Institute of Health and is appropriate for use in scientific publications.(4)
Sample types and collection for COVID-19 diagnostic tests
Added: 8 Feb 2021
Does COVID-19 diagnostic test performance vary according to whether respiratory swabs are selfcollected, or healthcare worker collected?
- Test performance of saliva compared with respiratory swabs in reverse transcription polymerase chain reaction (RT-PCR) nucleic acid tests
- Systematic reviews and eta-analyses have reported that saliva offers sensitivity and specificity for SARS-CoV-2 detection comparable to that of the current standard of nasopharyngeal and throat swabs and is a promising alternative for COVID-19 diagnosis.(1-5) Another meta-analysis reported that diagnostic tests based on salivary specimens are somewhat reliable, but relatively few studies have been carried out and such studies are characterised by low numbers and low sample power.(6)
- Generally, across individual studies there was high agreement between saliva samples and respiratory swabs. There were discrepancies in some studies where only saliva or respiratory swabs were positive.(7-43) The methodological quality of included studies varied.
- The overall mean viral load in saliva samples was lower in some studies.(7, 26) A scoping review concluded no significant difference in viral loads.(44)
- Self-collected versus healthcare worker collected respiratory swabs.
- Self-collected samples for SARS-CoV-2 RT-PCR is a potential strategy to reduce the burden of sample collection, save resources, and reduce the risk of exposure to healthcare workers.(45)
- A review from Alberta Health Services reported a study of 530 participants comparing selfswabbing to healthcare worker collection of nasopharyngeal swabs as a gold standard The sensitivity for detecting SARS-CoV-2 in patient collected tongue, nasal, and mid-turbinate samples was 89.8%, 94.0% and 96.2%, respectively.(45)
- Since the publication of this review, studies have found that generally, there is substantial agreement between self-collected swabs and swabs collected by healthcare workers. In some studies however there was greater sensitivity in healthcare worker collected samples while in others there was greater sensitivity in self-collected samples.(46-50)
- No sample method or specimen type could detect SARS-CoV-2 infections among all positive participants.(46, 48)
Ivermectin and COVID-19
Added: 23 Dec 2020
Updated: 15 Jan 2021
- 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 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
- 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
- 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.
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.