Human Anti-Ace2 Monoclonal Antibodies as Pan-Sarbecovirus Prophylactic Agents

Background: Human monoclonal antibodies from convalescent individuals that target the SARS-CoV-2 spike protein have been deployed as therapeutics against SARS-CoV-2. However, nearly all of these antibodies have been rendered obsolete by SARS-CoV-2 variants that evolved to resist similar, naturally occurring antibodies. Moreover, Most SARS-CoV-2 specific antibodies are inactive against divergent sarbecoviruses Methods: By immunizing mice that carry human immunoglobulin variable gene segments we generated a suite of fully human monoclonal antibodies that bind the human ACE2 receptor (hACE2) rather than the viral spike protein and were engineered to lack effector functions such as ADCC. Result(s): These ACE2 binding antibodies block infection by all hACE2 binding sarbecoviruses, including emergent SARS-CoV-2 variants, with a potency that of the most potent spike binding therapeutic antibodies. Structural and biochemical analyses revealed that the antibodies target an hACE2 epitope that engages SARS-CoV-2 spike. Importantly, the antibodies do not inhibit hACE2 enzymatic activity, nor do they induce ACE depletion from cell surfaces. The antibodies exhibit favorable pharmacology in human ACE2 knock in mice and provide near complete protection of hACE2 knock-in mice against SARS-CoV-2 infection. Conclusion(s): ACE2 binding antibodies should be useful prophylactic and treatment agents against any current and future SARS-CoV-2 variants, as well as hACE2-binding sarbecoviruses that might emerge as future pandemic threats.

Epigenetic features, methods, and implementations associated with COVID-19

The infection and life cycle of severe acute respiratory syndrome coronavirus 2 are widely studied, yet multiple gaps exist in the knowledge that affects therapeutic developments against coronavirus disease 2019 (COVID-19). Predominantly caused by a respiratory virus, COVID-19 is not restricted to the respiratory tract but affects multiple organs of the body including the cardiovascular, neurological, immunological, and renal systems. COVID-19 affects all age groups, although the elderly population inherently presenting with multiple comorbidities are disproportionately affected. The majority of the patients experience mild symptoms, although moderate, severe, and critical symptoms occur in a smaller group of patients. Interestingly, the effects of the disease can be acute or chronic and present an ongoing health care challenge. Epigenetic mechanisms of COVID-19 (DNA methylation, histone posttranslational modifications, histone citrullination, etc.) are an emerging field and present enormous potential toward the medical management of COVID-19. Angiotensin converting enzyme 2, an important protein in the cardiovascular system, is a receptor for viral entry into cells, and the epigenetic processes that regulate this protein have been widely studied. Identification of the epitranscriptomic profile has led to the identification of putative biomarkers for disease diagnosis and trials of novel epidrugs for targeted therapy. © 2023 Elsevier Inc. All rights reserved.

Current status of virtual reality simulation education for orthopedic residents: the need for a change in focus

Introduction Advances in technology are changing surgical education. Simulation provides an important adjunct to operative experience. This pedagogy has arguably become more important in light of the COVID-19 pandemic, with resultant reduction in operative exposure for trainees. Virtual reality (VR) simulators may provide significant contribution to experiential learning;however, much of the investigative focus to date has, correctly, been on establishing validity evidence for these constructs. The aim of this work was to perform a scoping review to assess the current status of VR simulation education to determine curricular development efforts for orthopedic residents. Methods With a trained medical librarian, searches of PubMed, EMBASE, and Web of Science were conducted for all articles in the last 10 years (September 2011–September 2021). Controlled vocabulary Medical Subject Headings (MeSH) terms and natural language developed with subject matter experts describing virtual reality or VR simulation and orthopedic training were used. Two trained reviewers evaluated all s for inclusion. Exclusion criteria were all articles that did not assess VR simulation education involving orthopedic residents. Data were extracted from the included full-text articles including: study design, type of participants, type of VR simulation, simulated orthopedic skill, type of educational event, learner assessment including Kirkpatrick's level, assessment of quality using the Medical Education Research Study Quality Instrument (MERSQI), and level of effectiveness (LoE). Results Initial search identified 1,394 articles, of which 61 were included in the final qualitative synthesis. The majority (54%) were published in 2019– 2021, 49% in Europe. The commonest VR simulator was ArthroS (23%) and the commonest simulated skill was knee arthroscopy (33%). The majority of studies (70%) focused on simulator validation. Twenty-three studies described an educational module or curriculum, and of the 21 (34%) educational modules, 43% were one-off events. Most modules (18/21, 86%) assessed learners at Kirkpatrick level 2. With regard to methodological quality, 44% of studies had MERSQI 11.5–15 and 89% of studies had LoE of 2. Two studies had LoE of 3. Conclusion Current literature pertaining to VR training for orthopedic residents is focused on establishing validity and rarely forms part of a curriculum. Where the focus is education, the majority are discrete educational modules and do not teach a comprehensive amalgam of orthopedic skills. This suggests focus is needed to embed VR simulation training within formal curricula efforts guided by the work of Kern, and assess the efficacy of these against patient outcomes.

Impact of the COVID-19 Pandemic on Patient Satisfaction After Total Joint Arthroplasty.

The coronavirus disease 2019 (COVID-19) pandemic impacted the inpatient experience before and after total joint arthroplasty (TJA). This study aimed to examine how these changes affected patient satisfaction following TJA as recorded by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) postdischarge surveys and comments at 2 large academic institutions. A retrospective review identified patients who completed HCAHPS surveys following primary and revision TJA at 2 academic institutions: 1 in a predominately rural southern state (Institution A) and 1 in a northeastern metropolitan city (Institution B). Patients were grouped by discharge date: pre-COVID-19 (April 1, 2019, to October 31, 2019) or COVID-19 affected (April 1, 2020, to October 31, 2020). Differences in demographics, survey responses, and comment sentiments and themes were collected and evaluated. The number of HCAHPS surveys completed increased between periods at Institution A but decreased at Institution B (Institution A, 61 vs 103; Institution B, 524 vs 296). Rates of top-box survey responses remained the same across the 2 periods. The number of comments decreased at Institution B (1977 vs 1012) but increased at Institution A (55 vs 88). During the COVID-19-affected period, there was a significant increase in the negative comment rate from Institution B (11.6% vs 14.8%, P=.013) and a significant decrease in the positive comment rate from Institution A (70.9% vs 44.3%, P<.001). There was an increase in negative patient sentiments following TJA during the COVID-19 pandemic as seen in qualitative comments but not quantitative responses. This suggests that certain aspects of the TJA patient experience were impacted by COVID-19. [Orthopedics. 2023;46(2):e105-e110.].

The Impact of Mandatory Pre-Operative Endocrinology Outpatient Consultation Before Elective Surgery in Patients with Diabetes Mellitus

Introduction: A multi-departmental quality improvement initiative by endocrinology, internal medicine, surgery, and anesthesia became effective, making it the standard of care to call for an outpatient endocrinology consult for diabetic patients undergoing elective surgery in our hospital. Aim: We tested our hypothesis that mandatory endocrinology consults prior to elective surgery decreases negative outcome parameters in patients with poorly controlled diabetes. Material and Method: Patients with diabetes mellitus (T2DM) who had an HbA1C 8% and above and who were planned to have elective surgery were seen by Endocrinology Service as an outpatient before the surgery date and were cleared until fasting glucose is less than 200 mg/dl or HbA1c is less than 8%. Retrospective analysis of 64 inpatient elective T2DM surgical patients, with no endocrine consults from 09/2019-12/2019 (Group I), comparing with 51 inpatient elective T2DM surgical patients from 09/2020-12/2020, with endocrine consults prior to surgery (Group II). Exclusion criteria: Emergency surgical patients and patients who received endocrine consults prior to surgery from September – December 2019. Primary outcome measure: Average capillary glucose, length of stay (LOS), the number of patients with hypoglycemic episodes (<70 mg/dl), hypoglycemia rate (number of glucose readings less than 70 mg/dl/the total number of capillary glucose measurements), readmission rate and infection rate. Mainly non-parametric statistical tests were utilized. Results: There were 64 patients without endocrinology consult in 2019 (Group I) and 51 patients with endocrinology consult in 2020 (Group II). Although it was a mandatory policy, only 11 out of 51 patients were consulted to endocrinology. There was no difference in baseline characteristics of age, gender, average HbA1c, and type of surgery between the two groups. Average glucose during hospital stay, the number of patients who had hypoglycemia (13% versus 6%), average LOS, readmission within 30 days and postoperative infection rate were not statistically different between Group I and II. In Group I hypoglycemic events were 2% of all the capillary glucose measurements performed (17 hypoglycemia out of 852) and in Group II hypoglycemic events were %0.5 (3 out of 653) of all the capillary glucose measurements performed during surgical admission (p<0.05). The number of hypoglycemic events were lower with preoperative endocrine consults. Limitations of this study include fewer elective surgeries in 2020 due to Covid-19. Conclusion: The number of hypoglycemic events were lower in patients with diabetes and preoperative mandatory endocrinology consultation. There was no difference in average glucose, LOS, the number of subjects with hypoglycemia, readmission or infection rate. The study should be repeated after more education about mandatory preoperative endocrinology consults to surgeons is delivered and after the COVID pandemic is over, when there are no restrictions on elective surgery.Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Human monoclonal antibodies to the spike subdomain 1 neutralize SARS-CoV-2 and its variants of concern

Progress in the fight against COVID-19 is jeopardized by the emergence of SARS-CoV-2 variants that diminish or abolish the efficacy of vaccines and antiviral monoclonal antibodies. Novel immune therapies are therefore needed, that are broadly effective against present and future coronavirus threats. In principle, this could be achieved by focusing on portions of the virus that are both functionally relevant and averse to change. The Subdomain 1 (SD1) of SARS-CoV-2 Spike protein is adjacent to the RBD and its sequence is conserved across SARS-CoV-2 variants, except for substitutions A570D in Alpha (B.1.1.7) and T547K in Omicron BA.1 (B.1.1.529). In order to specifically identify and study human antibodies targeting SD1, we designed a flow cytometry-based strategy that combines negative selection of B cells binding to the Receptor Binding Domain (RBD) with positive selection of those binding to SD1-RBD fusion protein. Among the 15 produced human monoclonal antibodies, 6 are SD1-specific. 3 of them cross-react with SD1-RBDs corresponding to all six variants of concern and 2 are neutralizing SARS-CoV-2 pseudovirus. Antibody sd1.040 also neutralizes Delta, Omicron BA.1 and Omicron BA.2 pseudovirus, synergizes with an antibody to the RBD for neutralization, and protects mice when present in a bispecific antibody. Thus, naturally occurring antibodies can neutralize SARS-CoV-2 variants by binding to SD1 and can act synergistically against SARS-CoV-2 in preclinical models.

CONSULTATION-LIAISON PSYCHIATRY RESPONSE TO THE IMPACT OF BUSHFIRES, VOLCANOS AND COVID-19 ON A STATE-WIDE BURN CENTRE

Background: The Statewide Burns Unit (SWBU) at Royal North Shore Hospital, one of two burns units in NSW, is a 12-bed unit run under the plastics/burns surgical team, nurse unit manager and multidisciplinary allied health team. Consultation-liaison (CL) psychiatry provides a part-time CL psychiatry registrar supervised by a parttime CL psychiatrist, who see and assess all admissions for pre-morbid and/or new and emerging acute mental health (MH) issues. Over 2019-2021 the SWBU saw significant numbers of burn injury patients because of several natural disasters and a spike in self-immolation during Sydney's COVID-19 lockdowns. The traumatic nature of the injuries was challenging for staff to manage over such a prolonged period. Senior team members were aware of the urgent need to (1) increase support for staff to minimise burnout risk and (2) improve access to longer-term psychological treatments for patients after discharge. Objectives: To report on the MH issues managed during this time, the management challenges and the process of significant service development, aiming to address unmet patient need as well as staffing, burnout and vicarious trauma. Methods: Naturalistic file review and NSW Statewide Burns registrar review supplemented by data from interviews with SWBU multidisciplinary team staff members. Conclusion: Trauma-informed and relational care is at the heart of the SWBU multidisciplinary team approach to care, requiring high-level service support and funding. CL psychiatry services can have a significant role in promoting service development, which sits under CanMEDS hats of clinical expert, advocate and leader.

The COVID-19 Pandemic and Centers of Medicaid and Medicare Services Regulatory Reform Impact on Total Hip Arthroplasty Metrics.

BACKGROUND: Shifts in demand, capacity, and site of service have impacted total hip arthroplasty (THA) volumes and revenues over the 2019-2021 time period. Moving THA off the inpatient-only (IPO) list and the COVID-19 pandemic has caused a shift in delivery away from inpatient services and a decrease in demand. METHODS: Medicare claims data were surveyed for the latest period available (April 1, 2020 to September 2020) and compared with a similar period in 2019 prior to THA removal from the IPO list and before the COVID-19 pandemic. Length of stay (LOS), admission status, site of service, discharge status, cost to CMS (Centers of Medicaid and Medicare Services), and racial disparities were analyzed. RESULTS: From 2019 to 2020, changes in primary THA metrics occurred (overall change in total joint arthroplasty [THA plus total knee arthroplasty metrics]): CMS THA volume decreased from 78,691 to 65,360, -16% (-22%); THA performed as an outpatient increased from 0% to 51% (141%); THA performed as same-day discharge increased from 3% to 12%, 325% (221%); overall LOS decreased from 1.91 to 1.46, -23% (-11%); inpatient LOS increased from 1.92 to 2.05, 7% (16%); outpatient LOS increased from 0.92 to 0.93, 1% (-12%); discharge home increased from 82% to 91%, 12.8% (11%); and CMS spending decreased from $1,033 million to $751 million, -27% (-27%). CONCLUSION: Medicare payments, LOS, discharge to facilities, and volume declined from 2019 to 2020 and were accelerated by IPO list changes and COVID-19 issues. Same-day discharge and hospital outpatient department cases also increased. THA metrics were not affected by race.

Worsening Arthroplasty Utilization With Widening Racial Variance During the COVID-19 Pandemic.

BACKGROUND: Elective arthroplasty surgery in the United States came to a near-complete halt in the spring of 2019 as a response to the COVID-19 pandemic. Racial disparity has been a long-term concern in healthcare with increased focus during the pandemic. The purpose of this study is to evaluate the effects of COVID-19 and race on arthroplasty utilization trends during the pandemic. METHODS: We used 2019 and 2020 Center for Medicare and Medicaid Service fee-for-service claims data to compare arthroplasty volumes prior to and during the COVID-19 pandemic. We compared overall arthroplasty utilization rates between 2019 and 2020 and then sought to determine the effect of race and COVID-19, both independently and combined. RESULTS: There was a decrease in primary total knee arthroplasty (-28%), primary total hip arthroplasty (-14%), primary total hip arthroplasty for fracture (-2%), and revision arthroplasty (-14%) utilization between 2019 and 2020. The highest decrease in overall arthroplasty utilization was in the Hispanic population (34% decrease vs 19% decrease in the White population). We found that a non-White patient was 39.9% (P < .001) less likely to receive a total joint arthroplasty prior to COVID-19. The COVID-19 pandemic further exacerbated the pre-existing racial differences in arthroplasty utilization by decreasing the probability of receiving a total joint arthroplasty for non-White patient by another 12.9% (P < .001). CONCLUSION: We found an overall decreased utilization rate of arthroplasty during the COVID-19 pandemic with further decrease noted in all non-White populations. This raises significant concern for worsening racial disparity in arthroplasty caused by the ongoing pandemic.

Racial and Ethnic Disparities in Hospitalization Outcomes Among Medicare Beneficiaries During the COVID-19 Pandemic

Key Points Question How did hospitalizations and racial and ethnic disparities in hospitalization outcomes change during the COVID-19 pandemic among patients with traditional Medicare? Findings In this cohort study using 100% traditional Medicare inpatient data, comprising 31 771 054 beneficiaries and 14 021 285 hospitalizations from January 2019 through February 2021, the decline in non–COVID-19 and emergence of COVID-19 hospitalizations during the pandemic was qualitatively similar among beneficiaries of different racial and ethnic minority groups. In-hospital mortality for patients with COVID-19 was higher in racial and ethnic minority groups than in White patients, driven by a Hispanic-White gap;mortality among non–COVID-19 hospitalizations also differentially increased among patients in racial and ethnic minority groups relative to White patients, driven by an increased Black-White gap. Meaning Racial and ethnic disparities in mortality were evident among COVID-19 hospitalizations and widened among non–COVID-19 hospitalizations among Medicare beneficiaries, motivating greater attention to health equity. This cohort study examines hospitalizations and differential changes in mortality and related outcomes by race and ethnicity among Medicare beneficiaries during the COVID-19 pandemic. Importance The COVID-19 pandemic has disproportionately affected racial and ethnic minority populations. However, racial and ethnic disparities in hospitalization outcomes during the pandemic—for both COVID-19 and non-COVID-19 hospitalizations—are poorly understood, especially among older populations. Objective To assess racial and ethnic differences in hospitalization outcomes during the COVID-19 pandemic among Medicare beneficiaries. Design, Setting, and Participants In the 100% traditional Medicare inpatient data, there were 31 771 054 unique beneficiaries in cross-section just before the pandemic (February 2020), among whom 26 225 623 were non-Hispanic White, 2 797 462 were Black, 692 994 were Hispanic, and 2 054 975 belonged to other racial and ethnic minority groups. There were 14 021 285 hospitalizations from January 2019 through February 2021, of which 11 353 581 were among non-Hispanic White beneficiaries, 1 656 856 among Black beneficiaries, 321 090 among Hispanic beneficiaries, and 689 758 among beneficiaries of other racial and ethnic minority groups. Sensitivity analyses tested expanded definitions of mortality and alternative model specifications. Exposures Race and ethnicity in Medicare claims from the Social Security Administration. Main Outcomes and Measures In-hospital mortality and mortality inclusive of discharges to hospice, deaths during 30-day readmissions, and 30-day all-cause mortality. Secondary outcomes included discharges to hospice and discharges to postacute care. Results The decline in non–COVID-19 and emergence of COVID-19 hospitalizations were qualitatively similar among beneficiaries of different racial and ethnic minority groups through February 2021. In-hospital COVID-19 mortality was not significantly different among Black patients relative to White patients, but was 3.5 percentage points higher among Hispanic patients (95% CI, 2.9-4.1;P < .001) and other racial and ethnic minority patients relative to White counterparts (95% CI, 3.0-4.1;P < .001). For non–COVID-19 hospitalizations, in-hospital mortality among Black patients increased by 0.5 percentage points more than it increased among White patients (95% CI, 0.3-0.6;P < .001), a 17.5% differential increase relative to the prepandemic baseline. This gap was robust to expanded definitions of mortality. Hispanic patients had similar differential increases in expanded definitions of mortality and model specification. Disparities in discharges to hospice and postacute care were evident. In aggregate across COVID-19 and non–COVID-19 hospitalizations, mortality differentially increased among raci l and ethnic minority populations during the pandemic. Conclusions and Relevance In this cohort study, racial and ethnic disparities in mortality were evident among COVID-19 hospitalizations and widened among non–COVID-19 hospitalizations, motivating greater attention to health equity.

POSB425 Methodological Challenges to Coronavirus Disease (COVID-19) Evidence Generation to Inform Health Technology Assessment (HTA)

Objectives: COVID-19 standard of care (SoC) has rapidly evolved, and many treatments are now in development which will require HTA following regulatory approval. Given the evolving COVID-19 treatment landscape, up-to-date evidence synthesis may challenge HTA. The aim of this study was to evaluate the methodological implications of the rapidly evolving evidence base required for HTA. Methods: A systematic literature review (SLR) in Embase and Medline of published clinical, economic and health-related quality of life (HRQoL) COVID-19 literature was conducted to generate evidence for HTA. Results: COVID-19 entries have increased exponentially compared to other diseases. A ‘COVID-19’ search in Embase generated 146,882 hits from October 2019-May 2021. Of these, 1,305 (estimated number per week (ENPW): 101) were published in 2019, 88,098 (ENPW: 1,694) in 2020 and 57,479 (ENPW: 2,699) in 2021. In comparison, there were 14,073 entries for multiple myeloma (MM), with 4,322 (ENPW: 333) in 2019, 7,224 (ENPW: 139) in 2020 and 2,527 (ENPW: 119) in 2021. An Embase and Medline search for COVID-19 clinical studies (October 2019 to May 2021), resulted in 7,279 entries, with only 63 (ENPW: 5) in 2019 (October to December), 3,746 (ENPW: 72) in 2020 and 3,470 (ENPW: 163) up to May 2021. In comparison, the MM SLR resulted in fewer clinical publications (1,964 entries, 614/47, 1,056/20 and 294/14 in 2019-2021). Similar trends were observed for economic and HRQoL studies. Overall, the COVID-19 SLR reported >70% clinical and >90% economic and HRQoL studies compared to a MM SLR intended for HTA. Conclusions: COVID-19 entries in databases are rapidly increasing weekly. Due to the evolving landscape and abundant evidence, challenges remain to synthesise evidence that is current and reflective of SoC. Based on this experience, a six-month time limit is recommended. COVID-19 evidence generation for HTA requires consensus around the requirements to ensure recommendations are based on up-to-date evidence.

Racial and Ethnic Disparities in Hospitalization Outcomes Among Medicare Beneficiaries During the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has disproportionately affected racial and ethnic minority populations. However, racial and ethnic disparities in hospitalization outcomes during the pandemic-for both COVID-19 and non-COVID-19 hospitalizations-are poorly understood, especially among older populations. Objective: To assess racial and ethnic differences in hospitalization outcomes during the COVID-19 pandemic among Medicare beneficiaries. Design Setting and Participants: In the 100% traditional Medicare inpatient data, there were 31 771 054 unique beneficiaries in cross-section just before the pandemic (February 2020), among whom 26 225 623 were non-Hispanic White, 2 797 462 were Black, 692 994 were Hispanic, and 2 054 975 belonged to other racial and ethnic minority groups. There were 14 021 285 hospitalizations from January 2019 through February 2021, of which 11 353 581 were among non-Hispanic White beneficiaries, 1 656 856 among Black beneficiaries, 321 090 among Hispanic beneficiaries, and 689 758 among beneficiaries of other racial and ethnic minority groups. Sensitivity analyses tested expanded definitions of mortality and alternative model specifications. Exposures: Race and ethnicity in Medicare claims from the Social Security Administration. Main Outcomes and Measures: In-hospital mortality and mortality inclusive of discharges to hospice, deaths during 30-day readmissions, and 30-day all-cause mortality. Secondary outcomes included discharges to hospice and discharges to postacute care. Results: The decline in non-COVID-19 and emergence of COVID-19 hospitalizations were qualitatively similar among beneficiaries of different racial and ethnic minority groups through February 2021. In-hospital COVID-19 mortality was not significantly different among Black patients relative to White patients, but was 3.5 percentage points higher among Hispanic patients (95% CI, 2.9-4.1; P < .001) and other racial and ethnic minority patients relative to White counterparts (95% CI, 3.0-4.1; P < .001). For non-COVID-19 hospitalizations, in-hospital mortality among Black patients increased by 0.5 percentage points more than it increased among White patients (95% CI, 0.3-0.6; P < .001), a 17.5% differential increase relative to the prepandemic baseline. This gap was robust to expanded definitions of mortality. Hispanic patients had similar differential increases in expanded definitions of mortality and model specification. Disparities in discharges to hospice and postacute care were evident. In aggregate across COVID-19 and non-COVID-19 hospitalizations, mortality differentially increased among racial and ethnic minority populations during the pandemic. Conclusions and Relevance: In this cohort study, racial and ethnic disparities in mortality were evident among COVID-19 hospitalizations and widened among non-COVID-19 hospitalizations, motivating greater attention to health equity.

American Association of Hip and Knee Surgeons Advocacy Efforts in Response to the SARS-CoV-2 Pandemic.

As soon as it became clear that our economy was going to be paralyzed by the SARS-CoV-2 pandemic, the American Association of Hip and Knee Surgeons leadership acted swiftly to ensure that our members were going to be eligible for the anticipated federal economic stimulus. The cessation of elective surgery, enacted in mid-March and necessary to stop the spread of the SARS-CoV-2 virus, would surely challenge the solvency of many of our members' practices. Although our advocacy efforts discussed further have helped, clearly more relief is needed. Fortunately, our mitigation efforts have led to a "flattening of the curve" and discussions have begun on when, where, and how to safely start elective surgery again.

Structures of SARS-CoV-2 antibodies induced by infection and mrna vaccines

In the space of less than a year, structural biology uncovered structure-function details for many of the proteins encoded by SARS-CoV-2, the coronavirus that has caused worldwide suffering and more than 1 million deaths since 2019. Remarkably, structures of the SARS-CoV-2 spike trimer were published in March 2020, only about 2 months after the viral sequence was available, aided by previous studies that established how to stabilize coronavirus spikes and the rapid turn-around time for solving structures by single-particle cryo-electron microscopy. Since then, other structures have revealed how spike binds to its angiotensin-converting enzyme 2 (ACE2) receptor, the specificities of polyclonal antibody responses in COVID-19-convalescent individuals, and how monoclonal neutralizing antibodies or designed protein inhibitors bind spike to prevent infection. Taken together, these structures have informed the development of potential therapeutics, including how pairs of monoclonal antibodies are chosen for treatment cocktails and guided structure-based engineering approaches to improve antibody potencies that are effective at lower doses and/or are resistant to viral mutations. With the rapid improvements in microscopes, cameras, and processing techniques, details of individual viral proteins (eg, spikes and ribonucleoproteins) can be resolved in their native context, providing more knowledge for researchers to use against this virus. Here, we will detail studies of neutralizing antibodies against the receptor binding domain induced by both infection by SARS-CoV-2 and by mRNA vaccines. Our data suggest that functionally similar antibodies are raised during vaccination and natural infection, and that the RBDs of spike trimers translated from the mRNA delivered by vaccination adopt both “up” and “down” conformations as observed on structures of trimer ectodomains and trimers on the surface of SARS-CoV-2 virions. Taken together, our work and the work of others illustrate the value of structural biology as a tool to gather information that will aid us in our battle to control the current pandemic and future outbreaks of deadly viruses.

Symptoms and laboratory manifestations of mild COVID-19 in a repatriated cruise ship cohort.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

The Initial Impact of COVID-19 on Total Hip and Knee Arthroplasty.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic caused a massive disruption in elective arthroplasty practice in the United States that to date has not been quantified. We sought to determine the impact of COVID-19 on arthroplasty volumes in the United States, how this varied across the country, and the resultant financial implications. METHODS: We conducted a retrospective analysis of Medicare fee-for-service beneficiaries undergoing primary and revision total knee arthroplasty (TKA) and total hip arthroplasty (THA) from January 1st through March 31st, 2020 with 74,080 TKAs and 54,975 THAs identified. We calculated the percent drop in average daily cases from before and after March 18, 2020. We then examined variation across states in arthroplasty case volumes as it related to reported COVID-19 cases, the impact of COVID-19 on length of stay and percentage of patients discharged home. Finally, we calculated the revenue impact on hospitals and surgeons. RESULTS: There was a steep decline in TKA and THA volumes in mid-March of 94% and 92%, respectively. There was a significant variation for arthroplasty case volumes across states. We found minimal change in length of stay except for primary THAs with fracture going from 5 + days to 4 days. We saw an increasing trend in discharge to home with the greatest effect in primary THAs with fracture. The total daily hospital Medicare revenue for arthroplasty declined by 87% and surgeon revenue decreased by 85%. CONCLUSION: The beginning of the COVID-19 pandemic caused a significant decrease in arthroplasty volumes in the Medicare population with a resultant substantial revenue loss for hospitals and surgeons.

Public Perceptions of Resuming Elective Surgery During the COVID-19 Pandemic.

BACKGROUND: Many U.S. health systems are grappling with how to safely resume elective surgery amid the COVID-19 pandemic. We used online crowdsourcing to explore public perceptions and concerns toward resuming elective surgery during the pandemic, and to determine factors associated with the preferred timing of surgery after health systems reopen. METHODS: A 21-question survey was completed by 722 members of the public using Amazon Mechanical Turk. Multivariable logistic regression analysis was performed to determine factors associated with the timing of preferred surgery after health systems reopen. RESULTS: Most (61%) participants were concerned with contracting COVID-19 during the surgical process, primarily during check-in and in waiting room areas, as well as through excessive interactions with staff. Overall, 57% would choose to have their surgery at a hospital over an outpatient surgery center. About 1 in 4 (27%) would feel comfortable undergoing elective surgery in the first month of health systems reopening. After multivariable adjustment, native English speaking (OR, 2.6; 95% CI, 1.04-6.4; P = .042), male sex (OR, 1.9; 95% CI, 1.3-2.7; P < .001), and Veterans Affairs insurance (OR, 4.5; 95% CI, 1.1-18.7; P = .036) were independent predictors of preferring earlier surgery. CONCLUSION: Women and non-native English speakers may be more hesitant to undergo elective surgery amid the COVID-19 pandemic. Despite concerns of contagion, more than half of the public favors a hospital setting over an outpatient surgery center for their elective surgery. Concerted efforts to minimize patient congestion and unnecessary face-to-face interactions may prove most effective in reducing public anxiety and concerns over the safety of resuming elective care.