Associations between COVID-19 and hospitalisation with respiratory and non-respiratory conditions: a record linkage study.

OBJECTIVES: To assess associations between SARS-CoV-2 infection and the incidence of hospitalisation with selected respiratory and non-respiratory conditions in a largely SARS-CoV-2 vaccine-naïve population . DESIGN, SETTING, PARTICIPANTS: Self-control case series; analysis of population-wide surveillance and administrative data for all laboratory-confirmed COVID-19 cases notified to the Victorian Department of Health (onset, 23 January 2020 - 31 May 2021; ie, prior to widespread vaccination rollout) and linked hospital admissions data (admission dates to 30 September 2021). MAIN OUTCOME MEASURES: Hospitalisation of people with acute COVID-19; incidence rate ratios (IRRs) comparing incidence of hospitalisations with defined conditions (including cardiac, cerebrovascular, venous thrombo-embolic, coagulative, and renal disorders) from three days before to within 89 days of onset of COVID-19 with incidence during baseline period (60-365 days prior to COVID-19 onset). RESULTS: A total of 20 594 COVID-19 cases were notified; 2992 people (14.5%) were hospitalised with COVID-19. The incidence of hospitalisation within 89 days of onset of COVID-19 was higher than during the baseline period for several conditions, including myocarditis and pericarditis (IRR, 14.8; 95% CI, 3.2-68.3), thrombocytopenia (IRR, 7.4; 95% CI, 4.4-12.5), pulmonary embolism (IRR, 6.4; 95% CI, 3.6-11.4), acute myocardial infarction (IRR, 3.9; 95% CI, 2.6-5.8), and cerebral infarction (IRR, 2.3; 95% CI, 1.4-3.9). CONCLUSION: SARS-CoV-2 infection is associated with higher incidence of hospitalisation with several respiratory and non-respiratory conditions. Our findings reinforce the value of COVID-19 mitigation measures such as vaccination, and awareness of these associations should assist the clinical management of people with histories of SARS-CoV-2 infection.

Serology study of healthcare workers following a hospital-based outbreak of COVID-19 in North West Tasmania, Australia, 2020.

Introduction: Healthcare facilities are high-risk settings for coronavirus disease 2019 (COVID-19) transmission. Early in the COVID-19 pandemic, the first large healthcare-associated outbreak within Australia occurred in Tasmania. Several operational research studies were conducted amongst workers from the implicated hospital campus, to learn more about COVID-19 transmission. Methods: Healthcare workers (HCWs) from the implicated hospital campus were invited to complete an online survey and participate in a serology study. Blood samples for serological testing were collected at approximately 12 weeks (round one) and eight months (round two) after the outbreak. A descriptive analysis was conducted of participant characteristics, serology results, and longevity of antibodies. Results: There were 261 HCWs in round one, of whom 44 (17%) were polymerase chain reaction (PCR) confirmed outbreak cases; 129 of the 261 (49%) participated in round two, of whom 34 (27%) were outbreak cases. The prevalence of positive antibodies at round one was 15% (n = 38) and at round two was 12% (n = 15). There were 15 participants (12%) who were seropositive in both rounds, with a further 9% (n = 12) of round two participants having equivocal results after previously being seropositive. Six HCWs not identified as cases during the outbreak were seropositive in round one, with three still seropositive in round two. Of those who participated in both rounds, 68% (n = 88) were seronegative at both time points. Discussion: Our findings demonstrate that serological testing after this large healthcare-associated COVID-19 outbreak complemented the findings of earlier diagnostic testing, with evidence of additional infections to those diagnosed when use of PCR testing had been restricted. The results also provide evidence of persisting SARS-CoV-2 antibody response eight months after an outbreak in an unvaccinated population. The high proportion of HCWs who remained seronegative is consistent with low community transmission in Tasmania after this outbreak.

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes.

Autoantibodies to multiple targets are found during acute COVID-19. Whether all, or some, persist after 6 months, and their correlation with sustained anti-SARS-CoV-2 immunity, is still controversial. Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.

Serving the Vulnerable: The World Health Organization's Scaled Support to Countries During the First Year of the COVID-19 Pandemic.

The Inter-Agency Standing Committee (IASC), created by the United Nations (UN) General Assembly in 1991, serves as the global humanitarian coordination forum of the UN s system. The IASC brings 18 agencies together, including the World Health Organization (WHO), for humanitarian preparedness and response policies and action. Early in the COVID-19 pandemic, the IASC recognized the importance of providing intensified support to countries with conflict, humanitarian, or complex emergencies due to their weak health systems and fragile contexts. A Global Humanitarian Response Plan (GHRP) was rapidly developed in March 2020, which reflected the international support needed for 63 target countries deemed to have humanitarian vulnerability. This paper assessed whether WHO provided intensified technical, financial, and commodity inputs to GHRP countries (n = 63) compared to non-GHRP countries (n = 131) in the first year of the COVID-19 pandemic. The analysis showed that WHO supported all 194 countries regardless of humanitarian vulnerability. Health commodities were supplied to most countries globally (86%), and WHO implemented most (67%) of the $1.268 billion spent in 2020 at country level. However, proportionally more GHRP countries received health commodities and nearly four times as much was spent in GHRP countries per capita compared to non-GHRP countries ($232 vs. $60 per 1,000 capita). In countries with WHO country offices (n = 149), proportionally more GHRP countries received WHO support for developing national response plans and monitoring frameworks, training of technical staff, facilitating logistics, publication of situation updates, and participation in research activities prior to the characterization of the pandemic or first in-country COVID-19 case. This affirms WHO's capacity to scale country support according to its humanitarian mandate. Further work is needed to assess the impact of WHO's inputs on health outcomes during the COVID-19 pandemic, which will strengthen WHO's scaled support to countries during future health emergencies.

COVID-19: Integrating genomic and epidemiological data to inform public health interventions and policy in Tasmania, Australia.

OBJECTIVE: We undertook an integrated analysis of genomic and epidemiological data to investigate a large health-care-associated outbreak of coronavirus disease 2019 (COVID-19) and to better understand the epidemiology of COVID-19 cases in Tasmania, Australia. METHODS: Epidemiological data collected on COVID-19 cases notified in Tasmania between 2 March and 15 May 2020, and positive samples of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or RNA extracted from the samples were included. Sequencing was conducted by tiled amplicon polymerase chain reaction with ARTIC v1 or v3 primers and Illumina sequencing. Consensus sequences were generated, sequences were aligned to a reference sequence and phylogenetic analysis was performed. Genomic clusters were determined and integrated with epidemiological data to provide additional information. RESULTS: All 231 COVID-19 cases notified in Tasmania during the study period and 266 SARS-CoV-2-positive samples, representing 217/231 (94%) notified cases, were included; 184/217 (84%) were clustered, 21/217 (10%) were unique and 12/217 (6%) could not be sequenced. Genomics confirmed the presence of seven clusters already identified through epidemiological links, clarified transmission networks in which the epidemiology had been unclear and identified one cluster that had not previously been recognized. DISCUSSION: Genomic analysis provided useful additional information on COVID-19 in Tasmania, including evidence of a large health-care-associated outbreak linked to an overseas cruise, the probable source of infection in cases with no previously identified epidemiological link and confirmation that there was no identified community transmission from other imported cases. Genomic insights are an important component of the response to COVID-19, and continuing genomic surveillance is warranted.

Lessons learnt from the first large outbreak of COVID-19 in health-care settings in Tasmania, Australia.

PROBLEM: One month after the initial case of coronavirus disease 2019 (COVID-19) in Tasmania, an island state of Australia, two health-care workers (HCWs) from a single regional hospital were notified to public health authorities following positive tests for SARS-CoV-2 nucleic acid. These were the first recognized cases in an outbreak that overwhelmed the hospital's ability to function. CONTEXT: The outbreak originated from two index cases. Both had returned to Tasmania following travel on a cruise ship and required hospital admission for management of COVID-19. A total of 138 cases were subsequently linked to this outbreak: 81 HCWs (most being nurses) and 23 patients across three hospitals, one resident of an aged-care facility and 33 close contacts. ACTION: The outbreak was controlled through the identification and isolation of cases, identification and quarantining of close contacts and their household members, closure of the affected facilities and community-level restrictions to reduce social mixing in the affected region. LESSONS LEARNT: Factors that were likely to have contributed to ongoing transmission in this setting included workplace practices that prevented adequate physical distancing, attending work while symptomatic, challenges in rapidly identifying contacts, mobility of staff and patients between facilities, and challenges in the implementation of infection control practices. DISCUSSION: Many commonly accepted hospital practices before the COVID-19 pandemic amplified the outbreak. The lessons learnt from this investigation changed work practices for HCWs and led to wider public health interventions in the management of potential primary and secondary contacts.

Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study.

BACKGROUND: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia. METHODS: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK. FINDINGS: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics and were included in our analysis. We identified 595 genomic clusters, with a median of five cases per cluster (IQR 2-11). Overall, samples from 11 503 (98·2%) of 11 711 cases clustered with another sample in Victoria, either within a genomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of 10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derived from a single incursion from hotel quarantine, with the outbreak lineage (transmission network G, lineage D.2) rapidly detected in other Australian states and territories. Phylodynamic analyses indicated that the epidemic growth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4 and July 9, 2020; 47·4 putative transmission events, per branch, per year [1/years; 95% credible interval 26·0-85·0]), was similar to that of other reported variants, such as B.1.1.7 in the UK (mean approximately 71·5 1/years). Strict interventions were implemented, and the outbreak lineage has not been detected in Australia since Oct 29, 2020. Subsequent cases represented independent international or interstate introductions, with limited local spread. INTERPRETATION: Our study highlights how rapid escalation of clonal outbreaks can occur from a single incursion. However, strict quarantine measures and decisive public health responses to emergent cases are effective, even with high epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies view and respond to COVID-19 outbreaks. FUNDING: The Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.