Evidence check
A rapid review outlining the available evidence on a discrete topic or question. Evidence includes grey and peer review literature. View all Evidence Checks by date of publication.
Archive Vaccine hesitancy
Added: 13 May 2021
Evidence in brief on vaccine hesitancy
- Vaccine hesitancy lies somewhere between complete acceptance and refusal of all vaccines. Factors that contribute to vaccine hesitancy include confidence in the vaccine and/or provider, complacency and convenience.
Archive Cerebral venous sinus thrombosis after AstraZeneca vaccination
Added: 30 Apr 2021
Evidence in brief on CVST after AstraZeneca vaccination
- In recent weeks there have been concerns about blood clots occurring in patients after they were given the AstraZeneca vaccine.(1) Most reports involved women under 55 years.(2)
- These reports included 18 cases of cerebral venous sinus thrombosis (as of 17 March 2021).(3)
- Cerebral venous sinus thrombosis (CVST) refers to the presence of a blood clot in the dural venous sinuses, which drain blood from the brain. Symptoms may include: headache, abnormal vision, any of the symptoms of stroke, such as weakness of the face and limbs on one side of the body and seizures.(4)
- CVST is rare, occurring at a rate of between two and five people per million.(4)
- Cerebral venous sinus thrombosis (CVST) can be a complication of COVID-19. A case series of 14 patients noted most received anticoagulation (91.7%) and a mortality rate of 45.5%.(5, 6)
- The main treatment for CVST is anticoagulation. There are, however, concerns that heparin is contraindicated in the rare cases of CVST following vaccination (particularly with AstraZeneca vaccine).(7)
- It has been proposed in Germany and Norway that post-AstraZeneca vaccination CVST may be similar to a syndrome known as heparin-induced thrombocytopaenia or HIT (sometimes referred to as heparin-induced thrombotic thrombocytopaenia or HITT.(8, 9)
- HIT is characterised by an anti-platelet factor 4 antibody response – leading to platelet consumption and thrombosis.(10)
- Notably, HIT features high thrombotic risk despite only mild to moderate thrombocytopenia. For example, the median platelet count nadir in HIT is approximately 55 to 70 × 109 /L, with a high proportion of patients (~30-50%) with platelet count nadirs >100 × 109 /L or even >150 × 109 /L developing thrombotic events.(11)
- It is diagnosed by a HITTS screen.(12)
- The standard anticoagulants used in HIT are argatroban (not currently registered in Australia), and bivalirudin.(10)
- The UK Medicines and Healthcare products Regulatory Agency (MHRA) is undertaking a detailed review of the five cases of CVST with low blood platelets that occurred in the UK, and also notes that these events can occur naturally.(13)
Archive COVID-19 vaccines clotting disorders
Added: 30 Apr 2021
Evidence in brief on COVID-19 vaccines and clotting disorders
- 8 April 2021: ATAGI (Australian Technical Advisory Group on Immunisation) recommends that COVID-19 vaccine by Pfizer is preferred over AstraZeneca in adults aged under 50 years.(1)
- 8 April 2021:Therapeutic Goods Administration notes investigation of unusual thrombosis in Australian vaccine recipient points to likely association, but insufficient evidence for firm conclusion.(2)
- 7 April 2021: European Medicines Agency review of 62 cases of cerebral venous sinus thrombosis and 24 cases of splanchnic vein thrombosis concludes unusual blood clots with low blood platelets should be listed as very rare side effects with AstraZeneca. Most cases occur in women under age 60 within two weeks of vaccination, although some of this may reflect greater exposure of such individuals due to targeting of particular populations for vaccine campaigns. Overall benefits outweigh risks.(3)
- March 2021: Canada and Germany suspend use of AstraZeneca vaccine in people younger than 55 and 60 years, respectively. UK Government says it is preferred that people under 30 years be offered an alternative vaccine.(4-6)
- There are however, concerns around complications with other COVID-19 vaccines and these have received less attention.
Archive Immunocompromised patients and COVID-19 vaccines
Added: 28 Apr 2021
What is the evidence on COVID-19 vaccination for immunocompromised patients including risks and adverse events, efficacy and advice from professional colleges?
- Evidence on COVID-19 vaccination in immunocompromised patients is limited. Small studies suggest that immunosuppression may be associated with attenuated immune response to SARS-CoV-2 in some patients after the first (1-3) and second vaccine dose.(4-7)
- One systematic review found inclusion of people with immunocompromised kidney disease in completed and ongoing COVID-19 vaccine trials was very low (6.5%) thus, vaccine immunogenicity is largely unknown.(9)
- Other articles included in this evidence check are mainly based on experience with vaccinations for other infectious diseases such as influenza, and on expert consensus from international professional societies.(13-17)
- The World Health Organization currently advises that it is safe to vaccinate immunocompromised patients with the Pifzer-BioNTech (BNT162b2) vaccine, Moderna mRNA-1273 vaccine, and AstraZeneca AZD1222 vaccine.(15)
- Expert consensus from international professional societies generally recommends vaccination for immunocompromised patients, as they are at increased risk of severe COVID-19 infection and benefits likely outweigh harms. Vaccination response may be reduced compared to nonimmunocompromised people.(17, 19-25)
- Inactivated, nucleic acid and protein subunit vaccines are considered safe, while special considerations are needed for live-attenuated vaccines. Non-replicating and replicating viral vector-based vaccines are considered safe by some professional groups, however a literature review concluded special considerations are needed for this type of vaccine.(23)
- Vaccination does not replace the need for other public health measures such as physical distancing.(27-30)
- Cancer: professional societies internationally recommend cancer patients, including those receiving active treatment, to be prioritised for vaccination. For patients undergoing certain therapy specific recommendations on timeframes between treatment and vaccination are suggested, including three months after haematopoietic cell transplantation or cell therapy, after the recovery of absolute neutrophil count for those receiving intensive cytotoxic chemotherapy, vaccinate before immunosuppressive chemotherapy, and whenever the vaccine becomes available for patients with solid tumour malignancies receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, and radiation therapy.(31-37)
- Inflammatory bowel disease: vaccination should be prioritised as benefits are likely to outweigh harms. Inactivated vaccines, such as mRNA, are safer than live-attenuated vaccine.(35-37)
- Kidney disease: most candidates (93.5%) with immunocompromised kidney disease were unqualified for participation in COVID-19 vaccine trials, so the vaccine immunogenicity is not well understood.(9) Guidance and recommendations regarding efficacy and timing of vaccination mainly rely on evidence from other vaccines.(27, 38) A recent cohort study found that the antiSARS-CoV-2 antibody titres in haemodialysis patients were significantly lower than those healthy participants after the second vaccination.(5)
- Liver diseases: vaccination is recommended to be given to patients prior to liver transplant or three to six months after. Success of vaccination depends on the staging of chronic liver disease at the time of immunisation.(28, 38-40)
- Multiple sclerosis: reduced vaccine responses are expected, window period for vaccination in patients receiving B cell-depleting therapies, such as Alemtuzumab, should be optimised in consultation with treating physicians.(2, 3) A case study reported the attenuated immune response to SARS-CoV-2 in a patient with relapsing-remitting multiple sclerosis after two doses of Pfizer vaccination.(4)
- Neuromuscular disorders: potential for reduced efficacy of vaccination, however benefits likely to outweigh risks.(42)
- Rheumatic diseases: the German Society for Rheumatology recommends not to discontinue or delay anti-rheumatic therapies in patients with well-controlled disease, while the Australian Rheumatology Association has provided the guidelines for surgery and vaccination is best to defer after rituximab infusion as advised by the individual’s rheumatologist.(13, 46) A prospective study showed that certain lymphocyte-modulating therapies were associated with diminished humoral vaccine response to SARS-CoV-2 in immunocompromised rheumatic patients.(8) A survey of patients found the response to the first dose of COVID-19 mRNA vaccine was generally localised and mild.(44)
- Transplant: guidance generally supports the benefits of vaccination and recommends adjustment to treatment agents for kidney transplantation.(15, 16) Two studies found that immunosuppression may be associated with a weaker anti-SARS-CoV-2 antibody response in kidney transplant recipients after the first mRNA vaccine dose.(1, 2) In another study, transplant recipients mainly experienced mild adverse events after receiving the first dose of mRNA vaccine.(3)
Archive COVID-19 rapid testing
Added: 19 Apr 2021
What is the efficacy of rapid, point-of-care tests for COVID-19?
- 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 diseasecomplemented 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.
Archive Quarantine measures
Added: 13 Apr 2021
What are the latest quarantine measures, including exemptions or differential measures based on risk stratification of the place of departure or travel history and vaccination status, for international travellers in different jurisdictions around the world?
- Most countries, except Canada and the United States, have differential quarantine measures or requirements based on travellers’ country of departure and travel history (that is places visited in the 14 or 21 consecutive days prior to entering the destination country).
- Exemption from mandatory quarantine is available in Australia, New Zealand, the United Kingdom, Singapore, France, Italy, Greece, Spain, Iceland, Cyprus and Norway for travellers arriving from a specified country or category of countries of low risk. Other conditions to exemptions may apply, such as a negative COVID-19 polymerase chain reaction (PCR) test upon arrival or within 24 hours, 48 hours or 72 hours prior to arrival.(1-11)
- Shorter quarantine duration than travellers arriving from the specified high-risk countries is available in Singapore and France if travellers arrived from certain categories of low-risk countries.
- Quarantine at home, or a suitable place instead of quarantine hotel or dedicated facility for the whole or part of the duration is available in the United Kingdom, Singapore, Italy, and Norway if travellers arrived from specific categories of countries.
- Exemption from mandatory quarantine is currently available in the United States, France, Greece, Spain, Norway, Iceland and Cyprus and from 5 July 2021 in Canada if a traveller is fully vaccinated as defined by the destination country. Other conditions to exemptions may apply, such as a negative COVID-19 PCR test upon arrival or within 24 hours or 72 hours prior to arrival.
Archive 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)
Archive AstraZeneca vaccine and blood clots
Added: 17 Mar 2021
Emerging evidence on AstraZeneca vaccine and blood clots
- The BMJ (11 March 2021): Denmark temporarily suspended use of the AstraZeneca vaccine after reports of blood clots and one death. Eight other countries including Norway, Iceland, Austria, and Italy have also suspended use of the vaccine. Since this publication, at least 15 other countries have suspended AstraZeneca vaccinations. The reported cases include one with multiple thrombosis, who died 10 days after vaccination. Another case was admitted to hospital with pulmonary embolism after being vaccinated. There were two other reports of thromboembolic event cases received by the EMA.
- European Medicines Agency (EMA) (11 March 2021): The EMA states there is currently no indication that vaccination has caused thromboembolic events. The safety committee states the vaccine’s benefits continue to outweigh its risks, and the vaccine can continue to be administered while investigation of cases of thromboembolic events is ongoing.
- Therapeutic Goods Administration (12 March 2021): The TGA has received no reports of blood clots following use of the AstraZeneca vaccine in Australia. Extensive international experience does not indicate an increased risk of blood clots associated with the vaccine.
- AstraZeneca (14 March 2021): A review of all available safety data of more than 17 million people vaccinated in the European Union and UK with the AstraZeneca vaccine has shown no evidence of an increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia
- in any defined age group, gender, batch
- or in any particular country.
- European Medicines Agency (15 March 2021): The overall number of thromboembolic events in vaccinated people does not seem to be higher than in the general population. While its investigation is ongoing, the EMA retains the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, outweigh the risks of side effects.
- UK Government (16 March): It has not been confirmed that the reports of blood clots were caused by the AstraZeneca COVID-19 vaccine. People should continue to get vaccinated.
- CNCB News (16 March): Many countries, including the UK, Canada and Australia are continuing to deploy the vaccine and seeking to reassure citizens about its benefits.
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. Evidence checks are archived a year after the date of publication.