Evidence Check - Epidemiology and transmission
Community transmission and hospital infection, stages of pandemic, immunity, vaccination.
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)
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.
Immunocompromised patients and COVID-19 vaccines
Added: 28 Apr 2021
- 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)
Added: 19 Apr 2021
- 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)
AstraZeneca vaccine and blood clots
Added: 17 Mar 2021
- 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.
Endemicity of SARS-CoV-2
Added: 17 Mar 2021
- 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.
AstraZeneca vaccine rollout
Added: 11 Mar 2021
- 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.
Emerging evidence about COVID-19 vaccines
Added: 25 Jan 2021
Updated: 5 Feb 2021
- There are four main vaccine types: whole virus, protein subunit, nucleic acid and viral vector
- To date, nine vaccines have been registered in one or more countries
- Results of phase 3 trials have been published for two messenger RNA (mRNA) vaccines (Pfizer/BioNTech and Moderna) and one vector vaccine (Oxford/Astra-Zeneca).
- There are different potential clinical endpoints for evaluating the efficacy of COVID-19 vaccines. These include SARS-CoV-2 infection, asymptomatic infection, COVID-19 (symptomatic disease), severe COVID-19, mortality and transmission.
- In the published phase 3 studies to date, efficacy is reported using symptomatic disease as the primary endpoint.
- Vaccine efficacy (using symptomatic disease as the primary endpoint) was 95.0% for the Pfizer/BioNTech vaccine, 94.1% for the Moderna vaccine and 70.4% for the Oxford/Astra-Zeneca vaccine (varying from 62.1% to 90.0% based on the schedule used).
- All three vaccines had an acceptable safety profile.
- It is not yet clear what vaccine efficacies and coverage levels will achieve herd immunity.
- According to the World Health Organization, the vaccines that have been approved to date should provide protection against emerging SARS-CoV-2 variants, as they elicit a broad immune response. Evidence is however emerging that there may be some immune escape
- The evidence on efficacy and effectiveness of COVID-19 vaccines is rapidly emerging. To date, there is limited to no information on efficacy re SARS-CoV-2 infection or asymptomatic infection, mortality and transmission. Nor is there published evidence on the impact of changes to dosage schedules, the duration of protection, different vaccination strategies or mixed vaccine use.
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.