Performance and Early Results from the Earth Surface Mineral Dust Source Investigation (EMIT) Imaging Spectroscopy Mission

The Earth Surface Mineral Dust Source Investigation (EMIT) acquires new observations of the Earth from a state-of-the-art, optically fast F/1.8 visible to short wavelength infrared imaging spectrometer with high signal-to-noise ratio and excellent spectroscopic uniformity. EMIT was launched to the International Space Station from Cape Canaveral, Florida, on July 14, 2022 local time. The EMIT instrument is the latest in a series of more than 30 imaging spectrometers and testbeds developed at the Jet Propulsion Laboratory, beginning with the Airborne Imaging Spectrometer that first flew in 1982. EMIT's science objectives use the spectral signatures of minerals observed across the Earth's arid and semi-arid lands containing dust sources to update the soil composition of advanced Earth System Models (ESMs) to better understand and reduce uncertainties in mineral dust aerosol radiative forcing at the local, regional, and global scale, now and in the future. EMIT has begun to collect and deliver high-quality mineral composition determinations for the arid land regions of our planet. Over 1 billion high-quality mineral determinations are expected over the course of the one-year nominal science mission. Currently, detailed knowledge of the composition of the Earth's mineral dust source regions is uncertain and traced to less than 5,000 surface sample mineralogical analyses. The development of the EMIT imaging spectrometer instrumentation was completed successfully, despite the severe impacts of the COVID-19 pandemic. The EMIT Science Data System is complete and running with the full set of algorithms required. These tested algorithms are open source and will be made available to the broader community. These include calibration to measured radiance, atmospheric correction to surface reflectance, mineral composition determination, aggregation to ESM resolution, and ESM runs to address the science objectives. In this paper, the instrument characteristics, ground calibration, in-orbit performance, and early science results are reported. © 2023 IEEE.

Multiplex Assays Enable Simultaneous Detection and Identification of SARS-CoV-2 Variants of Concern in Clinical and Wastewater Samples

The targeted screening and sequencing approaches for COVID-19 surveillance need to be adjusted to fit the evolving surveillance objectives which necessarily change over time. We present the development of variant screening assays that can be applied to new targets in a timely manner and enable multiplexing of targets for efficient implementation in the laboratory. By targeting the HV69/70 deletion for Alpha, K417N for Beta, K417T for Gamma, and HV69/70 deletion plus K417N for sub-variants BA.1, BA.3, BA.4, and BA.5 of Omicron, we achieved simultaneous detection and differentiation of Alpha, Beta, Gamma, and Omicron in a single assay. Targeting both T478K and P681R mutations enabled specific detection of the Delta variant. The multiplex assays used in combination, targeting K417N and T478K, specifically detected the Omicron sub-variant BA.2. The limits of detection for the five variants of concern were 4-16 copies of the viral RNA per reaction. Both assays achieved 100% clinical sensitivity and 100% specificity. Analyses of 377 clinical samples and 24 wastewater samples revealed the Delta variant in 100 clinical samples (nasopharyngeal and throat swab) collected in November 2021. Omicron BA.1 was detected in 79 nasopharyngeal swab samples collected in January 2022. Alpha, Beta, and Gamma variants were detected in 24 wastewater samples collected in May-June 2021 from two major cities of Alberta (Canada), and the results were consistent with the clinical cases of multiple variants reported in the community. © 2023 The Authors. Published by American Chemical Society.

Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective against severe disease. However, immune correlates of protection against BA.5 remain unknown. We report the immunogenicity and protective efficacy of vaccine regimens consisting of the vector-based Ad26.COV2.S vaccine and the adjuvanted spike ferritin nanoparticle (SpFN) vaccine against a high-dose, mismatched Omicron BA.5 challenge in macaques. The SpFNx3 and Ad26 + SpFNx2 regimens elicit higher antibody responses than Ad26x3, whereas the Ad26 + SpFNx2 and Ad26x3 regimens induce higher CD8 T cell responses than SpFNx3. The Ad26 + SpFNx2 regimen elicits the highest CD4 T cell responses. All three regimens suppress peak and day 4 viral loads in the respiratory tract, which correlate with both humoral and cellular immune responses. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques.

SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies.

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel® (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth.

Factors influencing COVID-19 health protective behaviours in Zambian university students with symptoms of low mood.

BACKGROUND: Health protective behaviours are crucial in the prevention of the spread of COVID-19, particularly in university students who typically live and study in large groups. Depression and anxiety are common in students and can impact young people's motivations to follow health advice. The study aims to assess the relationship between mental health and COVID-19 health-protective behaviours in Zambian university students with symptoms of low mood. METHODS: The study was a cross-sectional, online survey of Zambian university students. Participants were also invited to take part in a semi-structured interview to explore views about COVID-19 vaccination. Invitation emails were sent explaining the study aims and directed students who self-identified as having low mood in the past two weeks to an online survey. Measures included COVID-19 preventive behaviours, COVID-19-related self-efficacy, and Hospital and Anxiety Depression scale. RESULTS: A total of 620 students (n=308 female, n=306 male) participated in the study, with a mean participant age of 22.47±3.29 years (range 18-51). Students reported a mean protective behaviour score of 74.09/105 and 74% scored above the threshold for possible anxiety disorder. Three-way ANOVA showed lower COVID-19 protective behaviours in students with possible anxiety disorder (p=.024) and those with low self-efficacy (p<0.001). Only 168 (27%) said they would accept vaccination against COVID-19, with male students being twice as likely to be willing to accept COVID-19 vaccination (p<0.001). Of 50 students interviewed. 30 (60%) expressed fears about the vaccination and 16 (32%) were concerned about a lack of information. Only 8 (16%) participants expressed doubts about effectiveness. CONCLUSION: Students who self-identify as having symptoms of depression have high levels of anxiety. The results suggest that interventions to reduce anxiety and promote self-efficacy might enhance students' COVID-19 protective behaviours. Qualitative data provided insight into the high rates of vaccine hesitancy in this population.

Best-practices for preventing skin injury beneath personal protective equipment during the COVID-19 pandemic: A position paper from the National Pressure Injury Advisory Panel.

COVID-19 has infected millions of patients and impacted healthcare workers worldwide. Personal Protective Equipment (PPE) is a key component of protecting frontline clinicians against infection. The benefits of PPE far outweigh the risks, nonetheless, many clinicians are exhibiting skin injury caused by PPE worn incorrectly. These skin injuries, ranging from lesions to open wounds are concerning because they increase the susceptibility of viral infection and transmission to other individuals. Early into the COVID-19 pandemic (April 2020), the U. S. National Pressure Injury Advisory Panel (NPIAP) developed a series of position statements to improve wear-ability of PPE and protect healthcare professionals and their patients as safe from harm as possible under the circumstances. The NPIAP positions, which were formed by conducting a systematic review of what was known at the time, include: (a) Prepare skin before and after wearing PPE with skin sealants, barrier creams and moisturisers; (b) Frequent PPE offloading to relieve pressure and shear applied to skin; (c) treat visible skin injuries immediately caused by PPE to minimise future infection; (d) non-porous dressings may provide additional skin protection, but lack evidence; (e) health systems should take care to educate clinicians about placement and personal hygiene related to handling PPE. Throughout all of these practices, handwashing remains a top priority to handle PPE. These NPIAP positions provided early guidance to reduce the risk of skin injury caused by PPE based on available research regarding PPE injuries, a cautious application of evidence-based recommendations on prevention of device-related pressure injuries in patients and the expert opinion of the NPIAP Board of Directors. Clinicians who adhere to these recommendations reduce the prospects of skin damage and long-term effects (e.g. scarring). These simple steps to minimise the risk of skin injury and reduce the risk of coronavirus infection from PPE can help.

Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19.

Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 ± 0.880 vs 3.254 ± 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings.

Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity.

Despite rapid and ongoing vaccine and therapeutic development, SARS-CoV-2 continues to evolve and evade, presenting a need for next-generation diverse therapeutic modalities. Here we show that nurse sharks immunized with SARS-CoV-2 recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit a set of new antigen receptor antibody (IgNAR) molecules that target two non-overlapping conserved epitopes on the spike RBD. Representative shark antibody variable NAR-Fc chimeras (ShAbs) targeting either of the two epitopes mediate cell-effector functions, with high affinity to all SARS-CoV-2 viral variants of concern, including the divergent Omicron strains. The ShAbs potently cross-neutralize SARS-CoV-2 WA-1, Alpha, Beta, Delta, Omicron BA.1 and BA.5, and SARS-CoV-1 pseudoviruses, and confer protection against SARS-CoV-2 challenge in the K18-hACE2 transgenic mouse model. Structural definition of the RBD-ShAb01-ShAb02 complex enabled design and production of multi-specific nanobodies with enhanced neutralization capacity, and picomolar affinity to divergent sarbecovirus clade 1a, 1b and 2 RBD molecules. These shark nanobodies represent potent immunotherapeutics both for current use, and future sarbecovirus pandemic preparation.

Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants.

The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in E. coli, and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The E. coli-produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in E. coli and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of E. coli as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens.

Unraveling the pathophysiological role of angiostatin in COVID-19

Background: Angiostatin is a break-down product of plasmin(ogen). Physiologically, angiostatin is generated by platelets in an urokinase (uPA)-dependent manner. During normoxia angiostatin has anti-angiogenic/ anti-inflammatory effects and protects against lung injury, however during hypoxia/acidosis it is pro-apoptotic. In SARS-CoV infected mice, the uPA-plasminogen pathway was shown to be the most transcriptionally enriched regulating sublethal vs. lethal infection. Similarly, uPA has been shown to be transcriptionally upregulated in SARS-CoV- 2;however, the role of angiostatin has not been investigated. Aim(s): To assess role of angiostatin in COVID-19. Method(s): Plasma samples from COVID-negative controls and from hospitalized COVID-19 patients (n = 30) were collected (day 1, 7, 14, 28, 70) via the COVID-19 Surveillance Collaboration study. WHO clinical progression scale was used to assess COVID-19 severity. Angiostatin and plasminogen were quantified by immunoblot. VeroE6 cells were infected with SARS-CoV- 2 and treated with angiostatin (140 mug/ml) for 24h at pH 7.5 or 6.9. Cell death was quantified by both TUNEL and the percentage of detached cells. Immunofluorescent staining against the spike protein was used to confirm cellular infection. Result(s): Plasma angiostatin level was elevated in COVID-19 patients compared to COVID-negative controls at baseline. Both angiostatin and plasminogen increased with time of hospitalization in patients with severe COVID-19, but not with mild-to- moderate disease (p = 0.05;Fig.1). In preliminary cell culture experiments, at pH = 7.5 angiostatin decreased the percentage of detached (26 +/- 8% vs 67 +/- 5%;p = 0.0004) and TUNEL-positive VeroE6 (6 +/- 6 vs 11 +/- 7%;p = 0.07) following infection. Conversely, at pH = 6.9 angiostatin increased the percentage of detached cells following infection. Interestingly, angiostatin lowered the percentage of spike protein-positive Vero E6 at both pH (Fig.2). Conclusion(s): Angiostatin concentrations increase with disease progression in severe COVID-19. This likely reflects angiostatin's complex role in COVID-19 pathophysiology. Angiostatin promotes cell death in acidotic microenvironments (associated with severe Covid-19). Conversely, at physiological pH, angiostatin may have protective effects possibly by reducing viral entry and/or replication. (Figure Presented).

Protection against SARS-CoV-2 Omicron BA.1 variant challenge in macaques by prime-boost vaccination with Ad26.COV2.S and SpFN.

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and waning immunity call for next-generation vaccine strategies. Here, we assessed the immunogenicity and protective efficacy of two SARS-CoV-2 vaccines targeting the WA1/2020 spike protein, Ad26.COV2.S (Ad26) and Spike ferritin Nanoparticle (SpFN), in nonhuman primates, delivered as either a homologous (SpFN/SpFN and Ad26/Ad26) or heterologous (Ad26/SpFN) prime-boost regimen. The Ad26/SpFN regimen elicited the highest CD4 T cell and memory B cell responses, the SpFN/SpFN regimen generated the highest binding and neutralizing antibody responses, and the Ad26/Ad26 regimen generated the most robust CD8 T cell responses. Despite these differences, protective efficacy against SARS-CoV-2 Omicron BA.1 challenge was similar for all three regimens. After challenge, all vaccinated monkeys showed significantly reduced peak and day 4 viral loads in both bronchoalveolar lavage and nasal swabs as compared with sham animals. The efficacy conferred by these three immunologically distinct vaccine regimens suggests that both humoral and cellular immunity contribute to protection against SARS-CoV-2 Omicron challenge.

Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.

AIMS: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. METHODS: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. RESULTS: In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). CONCLUSIONS: The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.

Venous thromboembolism in critically ill patients with pneumonia in the pre-COVID-19 era: Data from a large public database.

Background: The magnitude of venous thromboembolism (VTE) risk in severe COVID-19 is a matter of debate because of study heterogeneity, changes in VTE management, and scarce evidence of VTE risk in critically ill patients with pneumonia in the pre-COVID-19 era. Objectives: To evaluate VTE risk in the pre-COVID-19 era in a large intensive care unit (ICU) database. Patients/Methods: Data from consecutive pneumonia patients admitted to the ICU were retrieved from the Medical Information Mart for Intensive Care III. VTE risk was described in the entire cohort and in subgroups. Results: Among 6842 pneumonia patients admitted to the ICU, 486 patients were diagnosed with VTE after a median of 3 (IQR 1-11) days in the ICU. The 30-day cumulative incidence of VTE was 7% and remained at this level across different age groups, sex, and type of ICU. After adjusting for death, the overall cumulative incidence of VTE was 5%. A total of 1788 patients received thromboprophylaxis (of 2958 for whom that data were available). VTE occurred in 10.7% (95% CI 9.0-12.6) of patients without thromboprophylaxis and in 6.4% (95% CI 5.4-7.6) of those with thromboprophylaxis. Mortality was 20.6% among patients with VTE and 19.2% among those without VTE. Conclusions: In the pre-COVID-19 era, VTE risk in ICU patients with pneumonia was high and decreased with thromboprophylaxis. These findings can serve as comparators for future studies aiming at evaluating the impact of COVID-19 or other emerging infections on VTE risk.

Humoral Response After a Third Dose of Sars-CoV-2 mRNA Vaccine in Transplant Recipients

Purpose: Prior studies demonstrated an increased immune response post-3rd COVID-19 vaccine dose when given 1-month post-2nd dose in solid organ transplant recipients (SOT). This study assessed whether a 3rd mRNA vaccine dose administered 6 months post-2nd dose enhanced humoral immune response in SOT. Method(s): A prospective cohort study was conducted of SOT, without prior COVID-19, who received 3 mRNA vaccine doses (BNT162b2 (Pfizer) or mRNA- 1273 (Moderna)). Primary outcome was a positive serologic response characterized by an anti-receptor-binding domain (RBD) antibody (Ab) level of >100 U/mL 4 weeks post-3rd dose (measured with the Roche Elecsys anti-SARS-CoV-2 immunoassay). Result(s): 175 SOT were enrolled: 48 (27%) heart, 72 (41%) lung, 51 (29%) kidney, 4 (2%) other SOT (Figure 1). A positive anti-RBD Ab level measured 4-weeks post-3rd vaccine dose was present in 105/175 (60%). In a multivariable model, age >60 years (adjusted odds ratio [aOR] 0.41;95% CI 0.19 to 0.87), heart (aOR 0.28;95% CI 0.10 to 0.76) or lung (aOR 0.20;95% CI 0.07 to 0.55) transplant, and mycophenolate use (aOR 0.24;95% CI 0.11 to 0.54) were independent risk factors for not developing a positive Ab post-3rd dose. Patients transplanted >10 years ago were more likely to have a positive Ab (aOR 4.95;95% CI 1.04 to 23.42). Those with a low positive Ab (>0.8 to <100 U/mL) post-2nd vaccine dose were more likely to have a positive Ab post-3rd dose than those with an undetectable Ab (<0.8 U/mL). But 26/105 (25%) participants with an undetectable Ab post-2nd dose developed an Ab of >100 U/ mL;9/26 (35%) developed an Ab >1000 U/mL (Figure 2). 4 (2%) SOT developed rejection within 30-days post-3rd dose. Conclusion(s): Despite the extended time interval of 6 months between the 2nd and 3rd doses, the proportion of non-responders (40%) in this study was similar to other studies when the 3rd dose was given 1-month post-2nd dose. These data suggest that a substantial proportion of SOT remain at risk for COVID-19 after 3 mRNA vaccine doses. Additional interventions need to be further studied, including monoclonal Ab as pre-exposure prophylaxis and 4th vaccine doses. (Figure Presented).

Practical and Ethical Considerations in Telehealth: Pitfalls and Opportunities

Telehealth has been a long-awaited advancement with the potential to improve efficiency, convenience, and quality in healthcare. However, as telehealth becomes integrated into routine clinical care, it is imperative to consider the practical and ethical implications that could undermine or devalue care delivery. The medical profession must ensure that it is implemented judiciously and with robust quality standards, guided by fair and equitable policies that balance patient autonomy with rigorous standards of care and access. Such a system must recognize the opportunity for more patient input as stakeholders to tailor care to their needs and preferences, while also acknowledging the risk of suboptimal care if convenience is prioritized over quality. More studies of optimal care models are needed to integrate data in terms of both stakeholder input and outcomes.

Use of Telemedicine for Type 1 Diabetes Care in the T1D Exchange Quality Improvement Collaborative (T1DX-QI) in 2021

Background: The COVID-pandemic accelerated adoption of telemedicine for diabetes care in 2020. We sought to describe the utilization of telemedicine across the T1DX-QI in 2021. Methods: Twenty four pediatric and nine adult clinics completed a survey about the proportion of televisits performed, center goals and processes in fall of 2021. Results: The majority of clinics reported performing between 11-25% (n=16, 48%) and 0-10% televisits (n=9, 27%) . The majority reported a pre-visit preparation workflow (n=24, 73%) , but most sites reported not having a staff member dedicated to supporting televisits (n=21, 64%) . No major differences in televisit use, goals, and processes were observed between pediatric and adult sites. For diabetes technology data downloads, the majority of clinics integrated data automatically into the EHR (n=25, 73%) . The major barriers to sustaining telemedicine practice across clinics were patient internet access, patient health disparities and access to device data (Figure 1) . Conclusion: More than one year into the pandemic the proportion of televisits performed by the T1DX-QI collaborative is modest. Clinic workflows have been implemented to support telemedicine but insufficient institutional support and technology barriers still represent an obstacle.

Genetic diversity of SARS-CoV-2 infections in Ghana from 2020-2021.

The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.

Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.