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Evidence Check

A rapid review outlining the available evidence on a discrete topic or question relating to the current COVID-19 pandemic. Evidence includes grey and peer review literature. View all Evidence Checks by date of publication.

COVID-19 vaccine and elective surgery

Added: 20 May 2021

What is the evidence on COVID-19 vaccination before elective surgery, including any recommendations regarding timing of vaccination?
  • Expert consensus from international professional societies generally recommend vaccinating patients against SARS-CoV-2 before elective surgery, as this may reduce the risk of COVID-19 complications and transmission of the virus during procedures.
  • Recommendations on the timing for preoperative COVID-19 vaccination is variable, ranging from a few days to weeks due to the unknown vaccine immunogenicity.
  • COVIDSurg, a modelling study based on data from almost 60,000 patients internationally, found that fewer people need to be vaccinated to prevent one death in surgical patients compared with the general population.
  • COVIDSurg estimated that globally, prioritising all surgical patients for preoperative vaccination ahead of the general population is projected to prevent an additional 58,687 COVID-19-related deaths in one year.
  • The timing for surgery, and potential for vaccine prioritisation, would need to take into account the context of the surgery and disease prevalence. For example, in some settings it may not be appropriate to prioritise surgical patients over vulnerable groups such as the elderly, and advice may vary for different surgeries.
  • The Royal College of Surgeons of England recommends that emergency surgery take place irrespective of COVID-19 immunisation status.

Vaccine hesitancy

Added: 13 May 2021

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.

COVID-19 vaccines clotting disorders

Added: 30 Apr 2021

  • 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.

Cerebral venous sinus thrombosis after AstraZeneca vaccination

Added: 30 Apr 2021

  • 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)

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)

Deep cleans

Added: 19 Apr 2021

Is deep cleaning necessary to limit the transmission of COVID-19?
  • In February 2020, the World Health Organisation (WHO) included fomites as a potential route of COVID-19 transmission.(1)
  • In July 2020, WHO updated its mode of transmission report, noting that despite consistent evidence of SARS-CoV-2 RNA on certain surfaces, there is no direct evidence of fomite transmission. However, fomite transmission is considered a likely mode of transmission for SARS-CoV-2.(2)
  • Despite no evidence of fomite transmission, there continues to be significant investment in deep-cleaning. A Nature perspective in January 2021 notes this may be due to: guidance from health agencies has not kept pace with the changing science, it is easier to clean surfaces than improve ventilation, and public expectations about levels of sanitisation.(3)
  • During the pandemic, the WHO and other health agencies recommended cleaning and disinfecting surfaces, particularly those frequently touched, such as on public transport.
  • NSW Health released specific cleaning guidance for areas where a confirmed or suspected case has been.(3, 4)
  • There are recommendations for increased cleaning in public areas such as on NSW public transport.(5)
  • Commentaries in the literature stress the importance of disinfection to reduce potential surface contamination.(3)
  • There is evidence about the effectiveness of different disinfectants at different concentrations.(6)
  • Organisations including the WHO have published lists of appropriate disinfectants related to COVID-19.(7)
  • Cleaning and disinfection protocols are more appropriate when context-specific.(8)
  • Other infection control measures such as hand washing are considered crucial in minimising disease transmission.(9)

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 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.

Quarantine measures

Added: 13 Apr 2021

What are the latest quarantine measures for different settings, such as point-of-entry at border settings, transportation or quarantine facilities, within different jurisdictions in Australia and around the world?
  • Most countries require people to have a COVID-19 test in the 72 hours before departure and on arrival. The exceptions are Australia which requires new arrivals to be tested within 48 hours and Taiwan which requires testing for symptomatic travellers only.
  • While Australia and New Zealand impose hotel quarantine, most other countries allow quarantine at home.
  • Apart from Australia, New Zealand and Taiwan which impose a minimum of 14 days of mandatory quarantine, other jurisdictions allow for various quarantine periods depending on the person’s travel history and certain conditions.
  • Transportation to quarantine facilities is arranged by the government in Australia and New Zealand. Government-appointed taxi providers or ‘epidemic prevention taxis’ are used for transportation in Singapore and Taiwan respectively. In some countries, use of private vehicles (Singapore and Iceland) or other public transport methods (Norway) are allowed under certain conditions.
  • Most countries require COVID-19 testing at the beginning and/or towards the end of the quarantine period.
  • Movement outside the quarantine room is allowed in some countries under specific conditions such as travelling to a COVID-19 test appointment (Singapore), seeking essential healthcare services (Iceland) or conducting necessary errands (Norway).
  • COVID-19 leaks from hotel quarantine programs were reported in Australia, New Zealand and Singapore.
  • Most countries imposed additional measures in response to new variants.

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.

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