Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile (preprint)

South America suffered large SARS-CoV-2 epidemics between 2020 and 2022 caused by multiple variants of interest and concern, some causing substantial morbidity and mortality. However, their transmission dynamics are poorly characterised. The epidemic situation in Chile enables us to investigate differences in the distribution and spread of variants Alpha, Gamma, Lambda, Mu and Delta. Chile implemented non-pharmaceutical interventions and an integrated genomic and epidemiological surveillance system that included airport and community surveillance to track SARS-CoV-2 variants. Here we combine viral genomic data and anonymised human mobility data from mobile phones to characterise the routes of importation of different variants into Chile, the relative contributions of airport-based importations to viral diversity versus land border crossings and test the impact of the mobility network on the diffusion of viral lineages within the country. We find that Alpha, Lambda and Mu were identified in Chile via airport surveillance six, four and five weeks ahead of their detection via community surveillance, respectively. Further, some variants that originated in South America were imported into Chile via land rather than international air travel, most notably Gamma. Different variants exhibited similar trends of viral dissemination throughout the country following their importation, and we show that the mobility network predicts the time of arrival of imported lineages to different Chilean comunas. Higher stringency of local NPIs was also associated with fewer domestic viral importations. Our results show how genomic surveillance combined with high resolution mobility data can help predict the multi-scale geographic expansion of emerging infectious diseases. Significance statementGlobal preparedness for pandemic threats requires an understanding of the global variations of spatiotemporal transmission dynamics. Regional differences are important because the local context sets the conditions for the unfolding of local epidemics, which in turn affect transmission dynamics at a broader scale. Knowledge gaps from the SARS-CoV-2 pandemic remain for regions like South America, where distinct sets of viral variants emerged and spread from late 2020 onwards, and where changes in human behaviour resulted in epidemics which differed from those observed in other regions. Our interdisciplinary analysis of the SARS-CoV-2 epidemic in Chile provides insights into the spatiotemporal trends of viral diffusion in the region which shed light on the drivers that can influence future epidemic waves and pandemics.

COVID-19 pandemic re-shaped the global dispersal of seasonal influenza viruses (preprint)

Understanding how the global dispersal patterns of seasonal influenza viruses were perturbed during and after the COVID-19 pandemic is needed to inform influenza intervention and vaccination strategies in the post-pandemic period. Although global human mobility has been identified as a key driver of influenza dispersal1, alongside climatic and evolutionary factors2,3, the impact of international travel restrictions on global influenza transmission and recovery remains unknown. Here we combine molecular, epidemiological, climatic, and international travel data within a phylodynamic framework to show that, despite human mobility remaining the principal driver of global influenza virus dissemination, the pandemics onset led to a shift in the international population structure and migration network of seasonal influenza lineages. We find that South Asia and Africa played important roles as exporters and phylogenetic trunk locations of influenza in 2020 and 2021, and we highlight the association between population movement, antigenic drift and persistence during the intensive non-pharmaceutical interventions (NPIs) phase. The influenza B/Yamagata lineage disappeared in a context of reduced relative genetic diversity, moderate lineage turnover, and lower positive selection pressure. Our results demonstrate that mobility perturbations reshaped the global dispersal dynamics of influenza viruses, with potential implications for vaccine design and genomic surveillance programmes. As the risk of future pandemics persists, our study provides an opportunity to assess the impact of NPIs during the pandemic on respiratory infectious diseases beyond the interplay between SARS-CoV-2 and influenza viruses.

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic (preprint)

Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Wholesale Seafood Market, the site with the most reported wildlife vendors in the city of Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected in the Huanan market in early 2020. We demonstrate that the SARS-CoV-2 genetic diversity linked to this market is consistent with market emergence, and find increased SARS-CoV-2 positivity near and within a particular wildlife stall. We identify wildlife DNA in all SARS-CoV-2 positive samples from this stall. This includes species such as civets, bamboo rats, porcupines, hedgehogs, and one species, raccoon dogs, known to be capable of SARS-CoV-2 transmission. We also detect other animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them to those from other markets. This analysis provides the genetic basis for a short list of potential intermediate hosts of SARS-CoV-2 to prioritize for retrospective serological testing and viral sampling.

The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2 (preprint)

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just ~1-3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics (preprint)

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of 'local' when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1 (preprint)

SARS-CoV-2 variants of concern (VOCs) arise against the backdrop of increasingly heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron genomes, we identified >6,000 independent introductions of the antigenically distinct virus into England and reconstructed the dispersal history of resulting local transmission. Travel restrictions on southern Africa did not reduce BA.1 importation intensity as secondary hubs became major exporters. We explored potential drivers of BA.1 spread across England and discovered an early period during which viral lineage movements mainly occurred between larger cities, followed by a multi-focal spatial expansion shaped by shorter distance mobility patterns. We also found evidence that disease incidence impacted human commuting behaviours around major travel hubs. Our results offer a detailed characterisation of processes that drive the invasion of an emerging VOC across multiple spatial scales and provide unique insights on the interplay between disease spread and human mobility.

Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations (preprint)

The emergence of SARS-CoV-2 variants has prompted the need for near real-time genomic surveillance to inform public health interventions. In response to this need, the global scientific community, through unprecedented effort, has sequenced over 7 million genomes as of December 2021. The extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info, a platform that can be used to track over 40 million combinations of PANGO lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials, and the general public. We describe the data pipelines that enable the scalable ingestion and standardization of heterogeneous data on SARS-CoV-2 variants, the server infrastructure that enables the dissemination of the processed data, and the client-side applications that provide intuitive visualizations of the underlying data.

Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions (preprint)

Regional connectivity and land-based travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions such as Europe. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the wider Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding from Europe in the early pandemic to more regional seeding for the period travel restrictions were in place. We show that land-based travel, particularly freight transport, drove introduction risk during the period of travel restrictions. Consistently, high regional connectivity and land-based travel also disproportionately drove Jordan's export risk to other Middle Eastern countries. Our findings emphasize regional connectedness and land-based travel as drivers of viral transmission in the Middle East. This demonstrates that strategies aiming to stop or slow the spread of viral introductions (including new variants) with travel restrictions need to prioritize risk from land-based travel alongside intercontinental air travel to be effective.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant (preprint)

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter- regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens (preprint)

Game animals are wildlife species often traded and consumed as exotic food, and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1725 game animals, representing 16 species and five mammalian orders, sampled across China. From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high risk viruses. We identified the transmission of Bat coronavirus HKU8 from a bat to a civet, as well as cross-species jumps of coronaviruses from bats to hedgehogs and from birds to porcupines. We similarly identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence.

National Population-Level Disparities in COVID-19 Mortality Across the Intersection of Race/Ethnicity and Sex in the United States (preprint)

Males and certain racial/ethnic minority groups have borne a disproportionate burden of COVID-19 mortality in the United States, and substantial scientific research has sought to quantify and characterize population-level disparities in COVID-19 mortality outcomes by sex and across categories of race/ethnicity. However, there has not yet been a national population-level study to quantify disparities in COVID-19 mortality outcomes across the intersection of these demographic dimensions. Here, we analyze a publicly available dataset from the National Center for Health Statistics comprising COVID-19 death counts stratified by race/ethnicity, sex, and age for the year 2020, calculating mortality rates for each race/ethnicity-sex-age stratum and age-adjusted mortality rates for each race/ethnicity-sex stratum, quantifying disparities in terms of mortality rate ratios and rate differences. Our results reveal persistently higher COVID-19 age-adjusted mortality rates for males compared to females within every racial/ethnic group, with notable variation in the magnitudes of the sex disparity by race/ethnicity. However, non-Hispanic Black, Hispanic, and non-Hispanic American Indian or Alaska Native females have higher age-adjusted mortality rates than non-Hispanic White and non-Hispanic Asian/Pacific Islander males. Moreover, persistent racial/ethnic disparities are observed among both males and females, with higher COVID-19 age-adjusted mortality rates observed for non-Hispanic Blacks, Hispanics, and non-Hispanic American Indian or Alaska Natives relative to non-Hispanic Whites.

Male-Female Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: A State-by-State Analysis (preprint)

Males are at higher risk relative to females of severe outcomes following COVID-19 infection. Focusing on COVID-19-attributable mortality in the United States (U.S.), we quantify and contrast years of potential life lost (YPLL) attributable to COVID-19 by sex based on data from the U.S. National Center for Health Statistics as of 31 March 2021, specifically by contrasting male and female percentages of total YPLL with their respective percent population shares and calculating age-adjusted male-to-female YPLL rate ratios both nationally and for each of the 50 states and the District of Columbia. Using YPLL before age 75 to anchor comparisons between males and females and a novel Monte Carlo simulation procedure to perform estimation and uncertainty quantification, our results reveal a near-universal pattern across states of higher COVID-19-attributable YPLL among males compared to females. Furthermore, the disproportionately high COVID-19 mortality burden among males is generally more pronounced when measuring mortality in terms of YPLL compared to age-irrespective death counts, reflecting dual phenomena of males dying from COVID-19 at higher rates and at systematically younger ages relative to females. The U.S. COVID-19 epidemic also offers lessons underscoring the importance of a public health environment that recognizes sex-specific needs as well as different patterns in risk factors, health behaviors, and responses to interventions between men and women. Public health strategies incorporating focused efforts to increase COVID-19 vaccinations among men are particularly urged.

Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study (preprint)

BackgroundAs large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation. We report population-based, age- and sex- specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. MethodsThis multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bells palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis. We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare. FindingsWe analysed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged [≥]85 years. InterpretationWe report robust baseline rates of prioritised AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines.

Alpha-1 blockers and susceptibility to COVID-19 in benign prostate hyperplasia patients : an international cohort study (preprint)

Alpha-1 blockers, often used to treat benign prostate hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storms release. We conducted a prevalent-user active-comparator cohort study to assess association between alpha-1 blocker use and risks of three COVID-19 outcomes: diagnosis, hospitalization, and hospitalization requiring intensive services. Our study included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH therapy during the period between November 2019 and January 2020, found in electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We found no differential risk for any of COVID-19 outcome, pointing to the need for further research on potential COVID-19 therapies.

Emergence of an early SARS-CoV-2 epidemic in the United States (preprint)

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States (preprint)

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia (preprint)

The coronavirus disease 2019 (COVID-19) epidemic in the United States has disproportionately impacted communities of color across the country. Focusing on COVID-19-attributable mortality, we expand upon a national comparative analysis of years of potential life lost (YPLL) attributable to COVID-19 by race/ethnicity (Bassett et al., 2020), estimating percentages of total YPLL for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, non-Hispanic Asians, and non-Hispanic American Indian or Alaska Natives, contrasting them with their respective percent population shares, as well as age-adjusted YPLL rate ratios - anchoring comparisons to non-Hispanic Whites - in each of 45 states and the District of Columbia using data from the National Center for Health Statistics as of December 30, 2020. Using a novel Monte Carlo simulation procedure to quantify estimation uncertainty, our results reveal substantial racial/ethnic disparities in COVID-19-attributable YPLL across states, with a prevailing pattern of non-Hispanic Blacks and Hispanics experiencing disproportionately high and non-Hispanic Whites experiencing disproportionately low COVID-19-attributable YPLL. Furthermore, observed disparities are generally more pronounced when measuring mortality in terms of YPLL compared to death counts, reflecting the greater intensity of the disparities at younger ages. We also find substantial state-to-state variability in the magnitudes of the estimated racial/ethnic disparities, suggesting that they are driven in large part by social determinants of health whose degree of association with race/ethnicity varies by state.

Characteristics and outcomes of 118,155 COVID-19 individuals with a history of cancer in the United States and Spain (preprint)

PurposeWe aimed to describe the demographics, cancer subtypes, comorbidities and outcomes of patients with a history of cancer with COVID-19 from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. MethodsWe conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: i) diagnosed with COVID-19, ii) hospitalized with COVID-19, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. ResultsWe included 118,155 patients with a cancer history in the COVID-19 diagnosed and 41,939 in the COVID-19 hospitalized cohorts. The most frequent cancer subtypes were prostate and breast cancer (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkins lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events. ConclusionPatients with a history of cancer and COVID-19 have advanced age, multiple comorbidities, and a high occurence of COVID-19-related events. Additionaly, hematological malignancies were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies.

Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 240,392 patients hospitalized with COVID-19 in the United States (preprint)

Objective To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). Design A network cohort study. Setting Six databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. Patients Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. Interventions Dialysis, tracheostomy, and ECMO. Measurements and Main Results 240,392 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 139,971 from IQVIA Open Claims, 29,061 from Optum EHR, 4,336 from OPTUM SES, 36,019 from Premier, and 8,118 from VA-OMOP). Across the six databases, 9,703 (4.04% [95% CI: 3.96% to 4.11%]) patients received dialysis, 1,681 (0.70% [0.67% to 0.73%]) had a tracheostomy, and 398 (0.17% [95% CI: 0.15% to 0.18%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was generally concentrated among patients who were younger, male, and with fewer comorbidities except for obesity. Tracheostomy was used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. Conclusion Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial and can be expected to continue grow given the continuing spread of the COVID-19.

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection (preprint)

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-{gamma}, IL-4, IL-6, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma} and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF- and IL-1{beta}) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.