BACKGROUND: The SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore. METHODS: This was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination. RESULTS: Two hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy. CONCLUSIONS: The Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.
Subject(s)COVID-19 , Multiple Sclerosis , Neuromyelitis Optica , Humans , Singapore/epidemiology , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Viral , Vaccination , Myelin-Oligodendrocyte Glycoprotein
Subject(s)COVID-19 , SARS-CoV-2 , Humans , Singapore/epidemiology , Pandemics , COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics
Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th February and 15th February. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a "delayed positive" test during isolation after initially testing negative, at least 7 days after last possible contact.
Subject(s)Contact Tracing , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Travel , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Disease Outbreaks , France/epidemiology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Quarantine , SARS-CoV-2 , Singapore , Spain/epidemiology , United Kingdom/epidemiology
Subject(s)Neurosurgery , Child , Humans , Neurosurgical Procedures , Singapore
We compared serial intervals and incubation periods for SARS-CoV-2 Omicron BA.1 and BA.2 subvariants and Delta variants in Singapore. Median incubation period was 3 days for BA.1 versus 4 days for Delta. Serial interval was 2 days for BA.1 and 3 days for BA.2 but 4 days for Delta.
Subject(s)COVID-19 , SARS-CoV-2 , Humans , Singapore/epidemiology , SARS-CoV-2/genetics , COVID-19/epidemiology , Infectious Disease Incubation Period
Subject(s)COVID-19 , Humans , COVID-19/epidemiology , Tertiary Care Centers , COVID-19 Testing , Singapore/epidemiology , Disease Outbreaks , Health Personnel
Refuse storage and collection systems are potential sources of food and harbourage areas for rodents which transmit pathogens. We examined the factors associated with rodent activity in public housing municipal waste collection premises in a highly urbanized city-state. We analysed data from April 2019 to March 2020 in mixed-effects logistic regression models to examine the independent factors associated with rodent activity in central refuse chute rooms (CRCs), individual refuse chute (IRC) bin chambers and bin centres. We accounted for within-year patterns, repeated measures and nested effects. We observed a heterogeneous spatial distribution of rodent activity. Rodent droppings were strongly associated with rodent activity in CRCs (aOR: 6.20, 95% CI: 4.20-9.15), bin centres (aOR: 3.61, 95% CI: 1.70-7.64) and IRC bin chambers (aOR: 90.84, 95% CI: 70.13-117.67). Gnaw marks were positively associated with rodent activity in CRCs (aOR: 5.61, 95% CI: 3.55-8.97) and IRC bin chambers (aOR: 2.05, 95% CI: 1.43-2.95), as were rub marks in CRCs (aOR: 5.04, 95% CI: 3.44-7.37) and IRC bin chambers (aOR: 3.07, 95% CI: 1.74-5.42). Each burrow increased the odds of rodent sightings in bin centres (aOR: 1.03, 95% CI: 1.00-1.06). The odds of rodent sightings in an IRC bin chamber increased with every additional bin chute chamber within the same block (aOR: 1.04, 95% CI: 1.01-1.07). We identified several factors that well predicted rodent activity in waste collection premises. Municipal estate managers with limited resources can adopt a risk-based approach in tailoring the focus of their rodent control interventions.
Subject(s)Garbage , Refuse Disposal , Singapore , Risk Factors , Logistic Models
Wastewater surveillance (WWS) has been globally recognised to be a useful tool in quantifying SARS-CoV-2 RNA at the community and residential levels without biases associated with case-reporting. The emergence of variants of concern (VOCs) have given rise to an unprecedented number of infections even though populations are increasingly vaccinated. This is because VOCs have been reported to possess higher transmissibility and can evade host immune responses. The B.1.1.529 lineage (Omicron) has severely disrupted global plans to return to normalcy. In this study, we developed an allele-specific (AS) RT-qPCR assay which simultaneously targets the stretch of deletions and mutations in the spike protein from position 24-27 for quantitative detection of Omicron BA.2. Together with previous assays that detect mutations associated with Omicron BA.1 (deletion at position 69 and 70) and all Omicron (mutation at position 493 and 498), we report the validation and time series of these assays from September 2021 to May 2022 using influent samples from two wastewater treatment plants and across four University campus sites in Singapore. Viral RNA concentrations at the treatment plants corroborate with locally reported clinical cases, AS RT-qPCR assays revealed co-incidence of Omicron BA.1 and BA.2 on 12 January 2022, almost two months after initial BA.1 detection in South Africa and Botswana. BA.2 became the dominant variant by the end of January 2022 and completely displaced BA.1 by mid-March 2022. University campus sites were similarly positive for BA.1 and/or BA.2 in the same week as first detection at the treatment plants, where BA.2 became rapidly established as the dominant lineage within three weeks. These results corroborate clinical incidence of the Omicron lineages in Singapore and indicate minimal silent circulation prior to January 2022. The subsequent simultaneous spread of both variant lineages followed strategic relaxation of safe management measures upon meeting nationwide vaccination goals.
Subject(s)COVID-19 , Humans , Incidence , RNA, Viral , SARS-CoV-2 , Singapore , Universities , Wastewater , Wastewater-Based Epidemiological Monitoring
BACKGROUND: To address the hospital bed demand for Delta and Omicron surges in Singapore, the National University Health System (NUHS) developed a COVID Virtual Ward to relieve bed pressures on its three acute hospitals-National University Hospital, Ng Teng Fong General Hospital, Alexandra Hospital. To serve a multilingual population, the COVID Virtual Ward featuring protocolized teleconsultation of high-risk patients, use of a vital signs chatbot, supplemented by home visits where necessary. This study aims to evaluate the safety, outcomes and utilisation of the Virtual Ward as a scalable response to COVID-19 surges. METHODS: This is a retrospective cohort study of all patients admitted to the COVID Virtual Ward between 23 September to 9 November 2021. Patients were defined as "early discharge" if they were referred from inpatient COVID-19 wards and "admission avoidance" if they were referred directly from primary care or emergency services. Patient demographics, utilisation measures and clinical outcomes were extracted from the electronic health record system. The primary outcomes were escalation to hospital and mortality. Use of the vital signs chatbot was evaluated by examining compliance levels, need for automated reminders and alerts triggered. Patient experience was evaluated using data extracted from a quality improvement feedback form. RESULTS: 238 patients were admitted to the COVID Virtual Ward from 23 September to 9 November, of whom 42% were male, 67.6% of Chinese ethnicity. 43.7% were over the age of 70, 20.5% were immunocompromised, and 36.6% were not fully vaccinated. 17.2% of patients were escalated to hospital and 2.1% of patients died. Patients who were escalated to hospital were more likely to be immunocompromised or to have a higher ISARIC 4C-Mortality Score. There were no missed deteriorations. All patients received teleconsults (median of 5 teleconsults per patient, IQR 3-7). 21.4% of patients received home visits. 77.7% of patients engaged with the vital signs chatbot, with a compliance rate of 84%. All patients would recommend the programme to others in their situation. CONCLUSIONS: Virtual Wards are a scalable, safe and patient-centered strategy to care for high risk COVID-19 patients at home. TRIAL REGISTRATION: NA.
Subject(s)COVID-19 , Emergency Service, Hospital , Humans , Male , Aged , Female , Retrospective Studies , Singapore , Hospitals, University
Background: Border control mitigates local infections but bears a heavy economic cost, especially for tourism-reliant countries. While studies have supported the efficacy of border control in suppressing cross-border transmission, the trade-off between costs from imported and secondary cases and from lost economic activities has not been studied. This case study of Singapore during the COVID-19 pandemic aims to understand the impacts of varying quarantine length and testing strategies on the economy and health system. Additionally, we explored the impact of permitting unvaccinated travelers to address emerging equity concerns. We assumed that community transmission is stable and vaccination rates are high enough that inbound travelers are not dissuaded from traveling. Methods: The number of travelers was predicted considering that longer quarantine reduces willingness to travel. A micro-simulation model predicted the number of COVID-19 cases among travelers, the resultant secondary cases, and the probability of being symptomatic in each group. The incremental net monetary benefit (INB) of Singapore was quantified under each border-opening policy compared to pre-opening status, based on tourism receipts, cost/profit from testing and quarantine, and cost and health loss due to COVID-19 cases. Results: Compared to polymerase chain reaction (PCR), rapid antigen test (ART) detects fewer imported cases but results in fewer secondary cases. Longer quarantine results in fewer cases but lower INB due to reduced tourism receipts. Assuming the proportion of unvaccinated travelers is small (8% locally and 24% globally), allowing unvaccinated travelers will accrue higher INB without exceeding the intensive care unit (ICU) capacity. The highest monthly INB from all travelers is $2,236.24 m, with 46.69 ICU cases per month, achieved with ARTs at pre-departure and on arrival without quarantine. The optimal policy in terms of highest INB is robust under changes to various model assumptions. Among all cost-benefit components, the top driver for INB is tourism receipts. Conclusions: With high vaccination rates locally and globally alongside stable community transmission, opening borders to travelers regardless of vaccination status will increase economic growth in the destination country. The caseloads remain manageable without exceeding ICU capacity, and costs of cases are offset by the economic value generated from travelers.
Subject(s)COVID-19 , Humans , Quarantine , Cost-Benefit Analysis , Singapore , Pandemics/prevention & control
Introduction: With the economic recession and pandemic fatigue, milder viral variants and higher vaccine coverage along the time lay the basis for lifting anti-COVID policies to restore COVID-19 normalcy. However, when and how to adjust the anti-COVID policies remain under debate in many countries. Methods: In this study, four countries (Singapore, South Korea, Australia, and New Zealand) and one region (Hong Kong SAR), that have shifted from the zero-COVID (ZC) policy to or close to the living-with-COVID (LWC) during or after the Omicron outbreak, were selected as research objects. All-cause mortality data were collected for these objects from 2009 to 2019. The expected mortality was estimated by a simple linear regression method. Excess mortality over time was calculated as the difference between the expected mortality and the observed mortality. Finally, percent excess mortality (PEM) was calculated as the excess mortality divided by the expected mortality. Results: In the examined four countries, PEM fluctuated around 0% and was lower than 10% most of the time under the ZC policy before 2022. After shifting to the LWC policy, all the examined countries increased the PEM. Briefly, countries with high population density (Singapore and South Korea) experienced an average PEM of 20-40% during the first half of 2022, and followed by a lower average PEM of 15-18% during the second half of 2022. For countries with low population density under the LWC policy, Australia experienced an average PEM of 39.85% during the first half of 2022, while New Zealand was the only country in our analysis that achieved no more than 10% in average PEM all the time. On the contrary, Hong Kong SAR under their ZC policy attained an average PEM of 71.14% during the first half of 2022, while its average PEM decreased to 9.19% in the second half of 2022 with LWC-like policy. Conclusion: PEM under different policies within each country/region overtime demonstrated that the mortality burden caused by COVID-19 had been reduced overtime. Moreover, anti-COVID policies are suggested to control the excess mortality to achieve as low as 10% in PEM.
Subject(s)COVID-19 , Humans , Hong Kong/epidemiology , Singapore/epidemiology , New Zealand , Republic of Korea/epidemiology , Policy
With countries progressing towards high COVID-19 vaccination rates, strategies for border reopening are required. This study focuses on Thailand and Singapore, two countries that share significant tourism visitation, to illustrate a framework for optimizing COVID-19 testing and quarantine policies for bilateral travel with a focus on economic recovery. The timeframe is the month of October 2021, when Thailand and Singapore were preparing to reopen borders for bilateral travel. This study was conducted to provide evidence for the border reopening policy decisions. Incremental net benefit (INB) compared to the pre-opening period was quantified through a willingness-to-travel model, a micro-simulation COVID-19 transmission model and an economic model accounting for medical and non-medical costs/benefits. Multiple testing and quarantine policies were examined, and Pareto optimal (PO) policies and the most influential components were identified. The highest possible INB for Thailand is US $125.94 million, under a PO policy with no quarantine but with antigen rapid tests (ARTs) pre-departure and upon arrival to enter both countries. The highest possible INB for Singapore is US $29.78 million, under another PO policy with no quarantine on both sides, no testing to enter Thailand, and ARTs pre-departure and upon arrival to enter Singapore. Tourism receipts and costs/profits of testing and quarantine have greater economic impacts than that from COVID-19 transmission. Provided healthcare systems have sufficient capacity, great economic benefits can be gained for both countries by relaxing border control measures.
Subject(s)COVID-19 , Humans , COVID-19 Testing , Thailand , Singapore , Pandemics/prevention & control , COVID-19 Vaccines , Travel , Policy
The COVID-19 pandemic infection control measures severely impacted mental well-being, allowing insight into possible protective parameters. With religion playing a role during challenging times, this study investigated theism and religiosity on the mental well-being of university students during the COVID19 pandemic and how social support and resilience can mediate this effect. One hundred eighty-five university students between 17 and 42 years old responded to online surveys on their theism, religious affiliations, religiosity, well-being, perceived support, and resilience. Pearson's correlations and single and sequential mediation analyses showed that theism did not significantly predict well-being (r = 0.049), but religiosity mediated the relationship (r = 0.432, effect size = 0.187). Sequential mediation analysis showed that resilience did not mediate the relationship between religiosity and well-being, but perceived social support significantly positively mediated religiosity and well-being with an effect size of 0.079. The findings reveal that factors, such as religiosity and social support could thus aid in the mental well-being of future challenging times such as the pandemic.
Subject(s)COVID-19 , Pandemics , Humans , Adolescent , Young Adult , Adult , Universities , Singapore , Religion , Students , Social Support
OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.
Subject(s)COVID-19 , Humans , COVID-19/diagnosis , COVID-19/epidemiology , SARS-CoV-2/genetics , Pandemics , Reinfection/diagnosis , Reinfection/epidemiology , Retrospective Studies , Singapore/epidemiology
BACKGROUND: In a rapidly digitalizing world, the inability of older adults to leverage digital technology has been associated with weaker social connections and poorer health outcomes. Despite the widespread digital adoption in Singapore, older adults, especially those of lower socioeconomic status (SES), still face difficulties in adopting information and communications technology and are typically digitally excluded. OBJECTIVE: We aimed to examine the impact of the volunteer-led, one-on-one, and home-based digital literacy program on digital literacy and health-related outcomes such as self-reported loneliness, social connectedness, quality of life, and well-being for older adults of low SES. METHODS: A nonrandomized controlled study was carried out in Singapore between July 2020 and November 2021 involving 138 digitally excluded community-dwelling older adults aged ≥55 years and of lower SES. Older adults awaiting participation in the program served as controls. Older adults under the intervention were equipped with a smartphone and cellular data, underwent fortnightly to monthly digital literacy training with volunteers to learn digital skills, and digitally connected to their existing social networks. Primary outcome was the improvement in self-reported digital literacy. Secondary outcomes included improvements in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, EQ-5D-3L and EQ visual analogue scale scores, and Personal Wellbeing Score. RESULTS: There were significant improvements in digital literacy scores in the intervention group as compared to controls (mean difference 2.28, 95% CI 1.37-3.20; P<.001). Through multiple linear regression analyses, this difference in digital literacy scores remained independently associated with group membership after adjusting for differences in baseline scores, age, gender, education, living arrangement, housing type, and baseline social connectivity and loneliness status. There was no statistically significant difference in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, Personal Wellbeing Score, or EQ-5D Utility and visual analogue scale score. CONCLUSIONS: This study adds to the growing research on digital inclusion by showing that a volunteer-led, one-on-one, and home-based digital literacy program contributed to increase digital literacy in older adults of low SES. Future studies should look into developing more older adult-friendly digital spaces and technology design to encourage continued digital adoption in older adults and, eventually, impact health-related outcomes.
Subject(s)Literacy , Quality of Life , Humans , Aged , Singapore , Income , Social Class
Transport drivers have high risk of exposure to SARS-CoV-2 during COVID-19 pandemic. Vaccines can reduce disease severity. However, COVID-19 vaccine perception among transport drivers is unknown. To identify the key factors influencing vaccine perception of transport drivers in Singapore, a cross-sectional pilot study was conducted. One hundred four completed survey responses were collected between September 2021 and February 2022. Using multivariable logistic regression, education, general vaccine knowledge and attitude, practice of social distancing, misinformation of rare vaccine side effects, and perceiving the pandemic situation to be severe were independently associated with vaccine perception. Despite high vaccination coverage, there were substantial poor vaccine perception, vaccine hesitancy, and unwillingness to take third dose. Vaccination rate may thus not be an accurate reflection of true vaccine acceptance. Communication strategies need to focus on correcting knowledge gaps, instilling collectivist attitudes, and highlighting the importance of vaccination over social distancing to enhance booster uptake rate.
Subject(s)COVID-19 Vaccines , COVID-19 , Humans , Pilot Projects , Singapore , Cross-Sectional Studies , Pandemics , SARS-CoV-2 , Vaccination , Perception
BACKGROUND: After-hours support from hospice providers is instrumental to patients with serious illness who choose to remain at home, particularly at end of life. Utilisation of out-of-hours support has been much characterised in terms of frequency and nature of calls, but more needs to be known to inform service customisation and resource allocation to optimise care. To this end, we stratify reasons for using the after-hours helpline according to time sensitivity, and to explore disease and person factors associated with urgent calls. METHOD: Electronic medical records for incoming calls from external parties outside workhours within a large home hospice in Singapore were analysed inductively, to identify patterns and associations along study objectives. Individual code books for caller type and call reasons were created and tested in vivo, and later administered to extracted data. Patients that accessed the helpline were tracked for different outcomes, including hospital admissions and on-call home visits. Logistic regression modelling was performed to categorise call reasons by urgency and to identify disease and person factors associated with time sensitive calls. RESULTS: More than 5,000 calls to the helpline were made over a two-year period (2019-2020), predominantly by family caregivers (88.4%). These were in relation to 2,303 unique patients (38.9% of total patients served). After-hours calls were made an average of 2.3 times by patients across various lengths of service. Only 11.9% of calls were deemed time sensitive or urgent, requiring home visits by on-call staff (4%) or resulting in admission to hospital (7.9%). The majority were managed by primary care teams on the next workday (65.1%) and the remainder sorted during the after-hours call itself (22.3%). Call reasons or presenting issues were classified into two groups according to urgency. Calls in the year 2020, from the younger patient, preferred place of death outside the home, and caller types other than patient or healthcare worker were significantly associated with urgent calls. CONCLUSION: Deeper characterisation of after-hours calls offers possibilities: service redesign for optimal resourcing and customised training for better care. Ultimately, planners, providers, and patients all stand to benefit.
Subject(s)Hospice Care , Hospices , House Calls , Humans , Singapore , Telephone
Subject(s)Feasibility Studies , Humans , Singapore/epidemiology , China
BACKGROUND: Dengue is a severe environmental public health challenge in tropical and subtropical regions. In Singapore, decreasing seroprevalence and herd immunity due to successful vector control has paradoxically led to increased transmission potential of the dengue virus. We have previously demonstrated that incompatible insect technique coupled with sterile insect technique (IIT-SIT), which involves the release of X-ray-irradiated male Wolbachia-infected mosquitoes, reduced the Aedes aegypti population by 98% and dengue incidence by 88%. This novel vector control tool is expected to be able to complement current vector control to mitigate the increasing threat of dengue on a larger scale. We propose a multi-site protocol to study the efficacy of IIT-SIT at reducing dengue incidence. METHODS/DESIGN: The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints: (1) odds ratio of Wolbachia exposure distribution (i.e., probability of living in an intervention cluster) among laboratory-confirmed reported dengue cases compared to test-negative controls and (2) laboratory-confirmed reported dengue counts normalized by population size in intervention versus non-intervention clusters. DISCUSSION: This study will provide evidence from a multi-site, randomized controlled trial for the efficacy of IIT-SIT in reducing dengue incidence. The trial will provide valuable information to estimate intervention efficacy for this novel vector control approach and guide plans for integration into national vector control programs in dengue-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682 . Registered on 16 August 2022. Retrospectively registered.