Critical Intelligence Unit

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 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?
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  • 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?
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  • 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?
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  • 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.
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  • 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
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  • 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.

Archive Endemicity of SARS-CoV-2

Added: 17 Mar 2021

What evidence is available about the likelihood that SARS-CoV-2 will become endemic?
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  • Endemicity refers to the extent to which a disease or infectious agent is always present within a given geographic area or population group.
  • Pre-COVID-19, four endemic coronaviruses (229E, NL63, OC43, and HKU1) were responsible for a large proportion of upper and lower respiratory tract infections.
  • Whether SARS-CoV-2, will also become endemic will be determined by the interplay between virus biology and immunity of the host population (see figure 1).
  • A weak adaptive immune response, waning immunity and viral immune escape can result in reinfection or infection in vaccinated populations. This leads to endemicity.(1)
  • A January 2021 survey of about 100 immunologists, infectious-disease researchers and virologists showed 90% thought SARS-CoV-2 will become endemic.(2)
  • Endemicity can take multiple forms. Several post-pandemic scenarios have been described.
  • Yearly outbreaks of SARS-CoV-2, if the duration of immunity proves to be similar to that of the other beta-coronaviruses (∼40 weeks).(1)
  • SARS-CoV-2 continues to circulate but becomes no more virulent than the common cold, with primary exposure in childhood.(3)
  • Apparent elimination of the virus followed by resurgence after a few years, if there is a longer immunity profile, coupled with a small degree of protective cross-immunity from other betacoronaviruses.(1, 4)
  • The nature of SARS-CoV-2 endemicity that emerges will require tailored and nuanced public health and policy responses in different jurisdictions.

Archive AstraZeneca vaccine rollout

Added: 11 Mar 2021

What evidence is emerging regarding the effectiveness of the AstraZeneca vaccine, particularly regarding hospitalisations in the United Kingdom (UK)?
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  • The AstraZeneca vaccine (AZD1222 / ChAdOx1) is a viral vector vaccine that can be stored at 2-8°C.
  • The original recommended schedule was two doses, 28 days apart.
  • The UK announced on 30 December 2020 its plan to administer two doses, 12 weeks apart.
  • In Australia, the Therapeutic Goods Administration has determined that the vaccine can be safely administered 4-12 weeks apart.
  • The AstraZeneca vaccine has an acceptable safety profile. Some European countries initially advised against use in older people due to lack of data. However, this is being reviewed and Germany has since approved the vaccine for those 65 years and over
  • BMJ (19 Feb 2021): The number of deaths in the UK within 28 days of a positive COVID-19 test reported as steadily falling. In the three weeks to 14 February 2021, deaths in care homes fell by 62% to a level previously seen around the end of October 2020. Hospital admissions fell in all age groups, however this may be as a result of the concurrent lockdown.
  • University of Edinburgh preprint (21 Feb 2021): Article showed that four weeks after the first doses of the Pfizer and AstraZeneca vaccines were administered in Scotland, the risk of hospitalisation from COVID-19 fell by up to 85% (95% confidence interval 76 to 91) and 94% (95% confidence interval 73 to 99), respectively
  • Lancet preprint (3 March 2021): Substantial reductions in the risk of COVID-19-related hospitalisation in elderly, frail patients with extensive co-morbid disease following a single dose of either Pfizer (71.4% reduction) or AstraZeneca (80.4% reduction) vaccines.
  • medRxiv preprint (4 March 2021): Single dose reported to be approximately 80% effective at preventing hospitalisation among people aged ≥70 years in UK. Significant reduction in symptomatic cases in older adults, with even greater protection against severe disease following a single dose of either Pfizer or AstraZeneca. Protection was maintained for the duration of follow-up (>6 weeks). Reports a clear effect of the vaccines against the UK variant of concern.

Archive COVID-19 pre-peer review articles

Added: 9 Mar 2021

What impact has the COVID-19 pandemic had on the publication of pre-peer review articles and subsequently, the quality of research evidence?
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  • Since the outbreak, there have been reports of a surge of pre-peer review articles on COVID-19.
  • Though challenges remain with regards to the speedy and widespread distribution of knowledge prior to ‘thorough vetting’, pre-peer review articles have been useful in highlighting and disseminating preliminary findings on rapidly evolving topics such as vaccines and viral variants.
  • For papers published on pre-reviewed platforms and subsequently in the peer-reviewed literature, there is no system in place to direct readers to the most up-to-date (peer-reviewed) version. This means that pre-peer review articles continue to be cited and ‘double referencing’ occurs, potentially drawing on superseded information.
  • The use of pre-peer review articles is a dynamic situation – snapshot analyses at various time points found: By the end of April 2020, more than 16,000 COVID-19 scientific articles had been published
  • among these, 6,753, were manuscripts hosted on a range of printing servers, including BioRxiv and MedRxiv (2,527 articles). By June 2020, it was estimated that around one in four of the scientific articles relating to COVID-19 were pre-peer review articles. By December 2020, it was estimated that more than 30,000 of the COVID-19 articles published in 2020 were pre-peer review articles, between 17% and 30% of total COVID-19 research papers depending on database searched. In MedRxiv, the medical science pre-peer review article publishing platform, ‘[m]ore than two-thirds of the preprints [..] were related to COVID-19’.
  • Characteristic of pre-peer review articles: Two studies reported that pre-peer review articles predominantly presented original results (89.8%), including from randomised controlled trials and systematic reviews.(7, 8) Case reports (6% academic versus 0.9% pre-peer review articles
  • p<0.001) and letters (17.4% academic versus 0.5% pre-peer review articles
  • p<0.001) accounted for a greater share of peer-reviewed compared to pre-peer review articles. In the first three months of the pandemic, COVID-19 articles including pre-peer review articles mostly covered the epidemiology of COVID-19 (35.7%), clinical aspects of infection (21.0%), preventative measures (12.8%), treatment options (12.5%), diagnostics (12.2%), mathematical modelling of disease transmission and mitigation (9.6%), and molecular biology and pathogenesis of SARS-CoV-2 (8.7%). A large proportion of COVID-19 pre-peer review articles were written by authors affiliated in China (51%)(7, 8). Or the articles were funded by sources in China (46%). A high number of contributions was also seen from the United States, the United Kingdom, and Italy.
  • Impact of preprints: Science journal described that the surge in pre-peer review articles during COVID-19 has created an ’information revolution’ in how research is communicated. It has been reported that such articles have been widely adopted for the dissemination and communication of COVID-19 research, and in turn, the pandemic has greatly impacted the science publishing landscape. A pre-peer reviewed study found that COVID-19 pre-peer review articles received a significant amount of attention from scientists, news organisations, the general public and policy-making bodies, representing a departure for how pre-peer review articles are normally shared. In July 2019, there were 6,800 article downloads and 25,300 abstract views in MedRxiv, whereas there were 2,356,900 and 5,853,600 in June 2020, respectively. Because of the speed of their release, it is surmised that pre-peer review articles, in comparison to peer-reviewed literature in the same topic area, may be driving discourse related to the ongoing COVID-19 outbreak.
  • Quality: There are concerns around the speed and rigour arising from the surge in COVID-19 pre-peer review articles, especially in the difficulty of ensuring quality and trustworthiness of such articles amidst expedited publishing. One study found that of 61% of COVID-19 publications had been reported in pre-peer review articles: 20% of these had an associated journal article, with median time to publication being 76 days. Twenty seven percent had more than one pre-peer review version. For studies with both a pre-peer review and peer-reviewed version, a median of 29% of total citations were attributed to the pre-peer review version instead of the article. The same study found that a total of 139 studies was reported in multiple evidence sources or versions of the same source and for 63 (45%), there was a change in at least one evidence component between or within sources. A different study found that only 18 (0.002%) pre-peer review articles were withdrawn after posting on MedRxiv, including 13 that were pandemic related. In a cross-sectional survey of medical specialists, the opinion on pre-peer review article archiving was divided, and only one-third believed such articles were useful.

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.

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