COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection.

Coronavirus Disease 2019 (COVID-19) has been the most severe public health challenge in this century. Two years after its emergence, the rapid development and deployment of effective COVID-19 vaccines have successfully controlled this pandemic and greatly reduced the risk of severe illness and death associated with COVID-19. However, due to its ability to rapidly evolve, the SARS-CoV-2 virus may never be eradicated, and there are many important new topics to work on if we need to live with this virus for a long time. To this end, we hope to provide essential knowledge for researchers who work on the improvement of future COVID-19 vaccines. In this review, we provided an up-to-date summary for current COVID-19 vaccines, discussed the biological basis and clinical impact of SARS-CoV-2 variants and subvariants, and analyzed the effectiveness of various vaccine booster regimens against different SARS-CoV-2 strains. Additionally, we reviewed potential mechanisms of vaccine-induced severe adverse events, summarized current studies regarding immune correlates of protection, and finally, discussed the development of next-generation vaccines.

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Lam et al. develop a model of SARS-CoV-2 infection in laboratory mice. This allows the researchers to study the threat of emerging variants in a more physiological context than cell culture systems. Interactions between SARS-CoV-2 variants and immunity is explored in the airway of mice.

Mass screening and the low rates of acute kidney injury among COVID-19 patients in Hong Kong

BACKGROUND AND AIMS: Renal involvement in COVID-19 under vigilant public health surveillance, including mass screening and early hospitalization is less wellcharacterized. We assessed renal involvement of COVID-19 patients in Hong Kong, including the association with risk factors, length of hospitalization, critical presentation and mortality. METHOD: Linked electronic records of all confirmed patients from 5 major designated hospitals were extracted. Primary outcome was the incidence of in-hospital AKI. Secondary outcomes were AKI-associated mortality, incident RRT, intensive care admission, prolonged hospitalization and disease course (defined as >90th percentile of hospitalization duration and duration from symptom onset to discharge, respectively), and change of eGFR. Patients were further stratified into being symptomatic or asymptomatic. RESULTS: Patients were characterized by young age (median:38.4, IQR:28.4-55.8 years old) and short time (Median:5, IQR:2-9 days) from symptom onset to admission. Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. AKI increased the odds of prolonged hospitalization and disease course by 2.0 and 3.5 folds, respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 ml/min/ 1.73m2 versus baseline (at admission) in the AKI and non-AKI groups, respectively. The incidence of AKI was comparable between asymptomatic (4.8%) and symptomatic (3.7%) patients. CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is low, which could be attributable to a vigilant screening program and early hospitalization. Among patients who developed in-hospital AKI, the duration of hospitalization is prolonged and kidney function impairment can persist for up to 6 months post-discharge. Mass surveillance for COVID-19 is warranted in identifying asymptomatic subjects for earlier AKI management.

The impact of patient demographics on the utilization of video vs telephonic care in a telemedicine clinic during the COVID-19 pandemic

Background: In response to the COVID-19 pandemic, stroke outpatient care was transformed to telemedicine (TM) through video (VTM) and telephonic (TPH) visits. While TM offers potential benefits over in-person visits for stroke patients, accessibility of VTM may be limited for patients at highest risk for poor outcomes. We recommended VTM for all patients, but offered TPH visits if patients did not have adequate equipment or declined VTM. We examined whether demographic variables influenced the TM visit type completed (VTM vs TPH) for patients seen during the pandemic. Methods: We conducted a retrospective review of charts for patients seen in our stroke clinic between 3/16/20 (fully operational TM) and 5/31/20. We determined visit type: VTM vs in-person vs TPH and abstracted demographic and clinical data. We focused on TM visits and used t-tests, Fisher's exact tests, and chi-squared as appropriate for univariate analyses and logistic regression for multivariate analyses. Results: Among 463 visits, 47 in-person visits were excluded, leaving 416 (328 VTM and 88 TPH). Mean age was 61.5 and by race/ethnicity: 42.9% non-Hispanic white (NHW), 36.9% non-Hispanic Black (NHB), 11.6% Hispanic, 4.3% Asian, and 4.3% other (Table 1). In univariate analyses, visit type was significantly associated with race (p = 0.024), insurance type (p=0.001), and visit type (new vs established). In adjusted analysis, NHB race was associated with 1.90 times higher odds (95% CI 1.09-3.32) of TPH vs VTM compared to NHW. Medicaid insurance was associated with 3.90 times higher odds (95% CI 1.54-9.88) of TPH vs VTM visit compared to private insurance. Conclusions: We found that NHB patients and patients with Medicaid were less likely to complete VTM visits compared to TPH. This suggests barriers to VTM based on race and insurance type and deserves further study. If video visits are superior to TPH visits for clinical care, these barriers may widen disparities in secondary stroke prevention during the pandemic.(Figure Presented).

Using telemedicine eliminates the weekend/after-hours effect in acute ischemic stroke patients receiving thrombolysis during a deadly pandemic

Stroke care has been shown to be worse for patients presenting overnight/weekends (off-hours) to centers compare to those presenting during business hours (on-hours).Telemedicine (TM) helps provide safe management of stroke patients. The UT Teleneurology (UTT) hub provides acute neurological coverage by stroke specialists to 18 spoke centers. To our knowledge, the effect of the Covid-19 pandemic on the “weekend effect” has not been studied. The objective is to compare TM consult volumes and time metrics of stroke patients who received tPA via TM off-hours with those on-hours during the pandemic. In a retrospective query of the UTT registry from 3/20 - 6/20, we identified 122 stroke patients who received tPA - 109 were included in our analysis - 2 were excluded after quality check, 11 were excluded as inpatient strokes. We compared baseline characteristics and time metrics between the off-hours (5pm-7:59am, weekends) and on-hours (weekdays 8am-4:59pm) patients (Table 1). We also compared the number of TM consults between the height of the pandemic (3/20 - 6/20) and the previous year (3/19 - 6/19). Of 109 patients, 72 were managed via TM during off-hours, 37 during on-hours. Baseline characteristics were similar between groups. There were no differences in time metrics including door to needle time. Of note, there was no difference in the number of acute TM consults or patients receiving tPA. There were fewer routine TM consults during the pandemic, and a trend toward fewer phone consults. There was no difference in time metrics between the patients treated off-hours vs on-hours in the pandemic period. TM may be advantageous over in-person neurology coverage during crises, and is consistent regardless of the hour/day. Contrary to other studies, the number of acute TM consults and patients receiving tPA did not differ between the study periods. Routine consults decreased during the pandemic - perhaps coinciding with state closure mandates/fewer hospitalized stroke patients. (Figure Presented).

Preserved acute stroke volumes and treatment metrics during the COVID 19 pandemic

Stroke is a devastating disease with high morbidity/mortality. Many studies have shown lower stroke volumes during the Covid 19 pandemic, with possible causes including fear of contracting the virus, limited hospital capacity, etc. Telemedicine (TM) helps provide safe management of stroke patients, and may be advantageous to in-person coverage during crises. The UT Teleneurology (UTT) hub provides acute neurological coverage by stroke specialists to 18 spoke centers. The impact of the pandemic on acute stroke volumes and care is ongoing and its effects should be studied further. The purpose of this study is to compare TM acute stroke volumes and time metrics between the Covid 19 era (March-June 2020) and the previous year (March-June 2019). In a retrospective query of the UTT registry from 3/19 - 6/19 and 3/20 - 6/20, we identified 294 stroke patients who received tPA - 273 were included in our analysis - 4 were excluded after quality check, 17 were excluded as inpatient strokes. We compared baseline and clinical characteristics, volumes, and time metrics between the periods (table 1). Of the 273 patients, 172 received tPA via TM during the 2019 period and 109 received tPA via TM during the 2020 period. Baseline and clinical characteristics were similar between the groups except for race. Of note, there were no differences in acute TM volumes or the number of patients receiving tPA. There was no difference in most metrics, including door to needle time. During the pandemic, camera to needle time was longer (3 minutes), and there was a trend towards longer last well to door time. There were no differences in the volume of acute TM consults, the number of patients receiving tPA, or door to needle time between the pandemic period and the previous year. Camera to needle time was slightly longer during the pandemic, perhaps representing more demands on hospital staff. The trend towards longer last well to door time could be due to public fear of presenting to the hospital during a deadly pandemic. (Figure Presented).

Impact of the COVID-19 pandemic in houston on stroke care in a health system of 10 stroke centers

Introduction: We assessed the impact of COVID-19 pandemic on stroke admissions and care metrics within a health system of 10 stroke centers, with 4 comprehensive stroke centers (CSC) in the greater Houston region. Methods: Between January-June 2019 and January-June 2020, we compared the proportion of ischemic strokes (total & direct CSC presentations) & intracerebral hemorrhage (ICH) relative to total admissions using logistic regression, and among the direct CSC presentations, we compared door to tPA and thrombectomy times using Wilcoxon Rank Sum. Results: A total of 4808 cases were assessed (Table 1). There was an initial drop of ∼30% in cases at the pandemic onset (Fig.1). Numerically fewer patients in the 2020 period were seen at primary and CSCs (Table 1). Compared to 2019, there was a significant reduction in transferred patients [N(%), 829 (36) vs. 637 (34), p=0.02], in hospital strokes [N(%), 111 (5) vs. 69 (4), p=0.04], and mild strokes (NIHSS 1-5) [N (%), 891 (43) vs. 635 (40),p=0.02], and no significant differences in the proportions of total ischemic strokes [OR (95% CI)=0.92 (0.79, 1.06), p=0.23], direct CSC presentations [OR (95% CI) =0.96 (0.86, 1.08), p=0.48] and ICH [OR (95% CI) =1.14 (0.98, 1.33), p=0.08] in 2020 (Fig. 1). Among the direct ischemic strokes at CSCs, there were similar mean (SD) (mins) door to tPA [44 (17) vs. 42 (17), p=0.14] but significantly prolonged door to thrombectomy times [94 (15) vs. 85 (20), p=0.005] in 2020. Conclusion: COVID-19 pandemic led to reduced mild stroke admissions, transfers and in hospital stroke alerts, & prolonged door to thrombectomy times. Identifying reasons to mitigate this discrepancy is crucial for next pandemic preparedness. (Figure Presented).

A novel pseudovirus-based mouse model of SARS-CoV-2 infection to test COVID-19 interventions

BACKGROUND: The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities. Here we describe the development of a preclinical animal model using intranasal administration of ACE2 followed by non-infectious SARS-CoV-2 pseudovirus (PsV) challenge. METHODS: To specifically generate our SARS-CoV-2 PsV, we used a lentivirus system. Following co-transfection with a packaging plasmid containing HIV Gag and Pol, luciferase-expressing lentiviruses, and a plasmid carrying the SARS-CoV-2 spike protein, SARS-CoV-2 PsVs can be isolated and purified. To better understand and maximize the infectivity of SARS-CoV-2 PsV, we generated PsV carrying spike protein variants known to have varying human ACE2 binding properties, including 19 deletion (19del) and 19del + D614G. RESULTS: Our system demonstrated the ability of PsVs to infect the respiratory passage of mice following intranasal hACE2 transduction. Additionally, we demonstrate in vitro and in vivo manipulability of our system using recombinant receptor-binding domain protein to prevent PsV infection. CONCLUSIONS: Our PsV system is able to model SARS-CoV-2 infections in a preclinical mouse model and can be used to test interventions or preventative treatments. We believe that this method can be extended to work in various mouse strains or to model infection with different coronaviruses. A simple in vivo system such as our model is crucial for rapidly and effectively responding to the current COVID-19 pandemic in addition to preparing for future potential coronavirus outbreaks.

Coronavirus vaccine development: from SARS and MERS to COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.

Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31st December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as 'close' or 'casual' for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of 'close contact'. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.

Peculiar Aspects of Patients with Inherited Arrhythmias during the COVID-19 Pandemic

Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient's own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.