Health Care Utilization and Death in Patients With Heart Failure During the COVID-19 Pandemic.

Objective: To compare the 1-year health care utilization and mortality in persons living with heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. Patients and Methods: Residents of a 9-county area in southeastern Minnesota aged 18 years or older with a HF diagnosis on January 1, 2019; January 1, 2020; and January 1, 2021, were identified and followed up for 1-year for vital status, emergency department (ED) visits, and hospitalizations. Results: We identified 5631 patients with HF (mean age, 76 years; 53% men) on January 1, 2019, 5996 patients (mean age, 76 years; 52% men) on January 1, 2020, and 6162 patients (mean age, 75 years; 54% men) on January 1, 2021. After adjustment for comorbidities and risk factors, patients with HF in 2020 and patients with HF in 2021 experienced similar risks of mortality compared with those in 2019. After adjustment, patients with HF in 2020 and 2021 were less likely to experience all-cause hospitalizations (2020: rate ratio [RR], 0.88; 95% CI, 0.81-0.95; 2021: RR, 0.90; 95% CI, 0.83-0.97) compared with patients in 2019. Patients with HF in 2020 were also less likely to experience ED visits (RR, 0.85; 95% CI, 0.80-0.92). Conclusion: In this large population-based study in southeastern Minnesota, we observed an approximately 10% decrease in hospitalizations among patients with HF in 2020 and 2021 and a 15% decrease in ED visits in 2020 compared with those in 2019. Despite the change in health care utilization, we found no difference in the 1-year mortality between patients with HF in 2020 and those in 2021 compared with those in 2019. It is unknown whether any longer-term consequences will be observed.

The era of Cas12 and Cas13 CRISPR-based disease diagnosis.

Clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein (Cas) systems, since their discovery, have found growing applications in cell imaging, transcription modulation, therapeutics and diagnostics. Discovery of Cas12 and Cas13 have brought a new dimension to the field of disease diagnosis. These endonucleases have been extensively used for diagnosis of viral diseases in humans and animals and to a lesser extent in plants. The exigency of SARS-CoV-2 pandemic has highlighted the potential of CRISPR-Cas systems and sparked the development of innovative point-of-care diagnostic technologies. Rapid adaptation of CRISPR-chemistry combined with sensitive read-outs for emerging pathogens make them ideal candidates for detection and management of diseases in future. CRISPR-based approaches have been recruited for the challenging task of cancer detection and prognosis. It stands to reason that the field of CRISPR-Cas-based diagnosis is likely to expand with Cas12 and Cas13 playing a pivotal role. Here we focus exclusively on Cas12- and Cas13-based molecular diagnosis in humans, animals and plants including the detection of SARS-coronavirus. The CRISPR-based diagnosis of plant and animal diseases have not found adequate mention in previous reviews. We discuss various advancements, the potential shortfalls and challenges in the widespread adaptation of this technology for disease diagnosis.

Health Care Utilization and Death in Heart Failure Patients During the COVID-19 Pandemic

Objective To compare 1-year health care utilization and mortality between persons living with heart failure (HF) prior to vs. during the coronavirus disease 2019 (COVID-19) pandemic. Patients and Methods Residents of a 9-county area in southeastern Minnesota ≥18 years with a HF diagnosis on January 1, 2019, January 1, 2020, and January 1, 2021, were identified and followed 1-year for vital status, emergency department (ED) visits, and hospitalizations. Results We identified 5631 patients with HF (mean age 76, 53% male) on January 1, 2019, 5996 (mean age 76, 52% male) on January 1, 2020, and 6162 (mean age 75, 54% male) on January 1, 2021. After adjustment for comorbidities and risk factors, HF patients in 2020 had a similar risk of mortality compared to patients in 2019, as did patients in 2021. After adjustment, HF patients in 2020 and 2021 were less likely to have all-cause hospitalizations (2020 HR, 0.88;95% CI, 0.81-0.95;2021 HR, 0.90;95% CI, 0.83-0.97) compared to patients in 2019. HF patients in 2020 were also less likely to have ED visits (HR, 0.85;95% CI, 0.80-0.92). Conclusion In a large population-based study in southeastern MN, we observed an approximately 10% decrease in hospitalizations among patients with HF in 2020 and 2021, and a 15% decrease in ED visits in 2020 compared to 2019. Despite the change in health care utilization, we found no difference in 1-year mortality between patients with HF in 2020 or 2021. It is unknown if any longer-term consequences will be observed.

High titre neutralizing antibodies in response to SARS-CoV-2 infection require RBD-specific CD4 T cells that include proliferative memory cells.

Background: Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden. Methods: We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects. Findings: Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres. Interpretation: Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.

Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19.

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

An improved, simple and field-deployable CRISPR-Cas12a assay for the detection of SARS-CoV-2.

AIMS: The RT-PCR is the most popular confirmatory test for SARS-CoV-2. It is sensitive, but high instrumentation cost makes it difficult for use outside routine clinical setup. This has necessitated the development of alternative methods such as CRISPR-based DETECTR method which uses lateral flow technology. Although accurate and sensitive, this method is limited by complex steps and recurrent cost of high-quality lateral flow strips. The main goal of this study was to improve the Cas12a-based SARS-CoV-2 DETECTR method and develop a portable and field-deployable system to reduce the recurring consumable cost. METHODS AND RESULTS: Specific regions of N and E genes from SARS-CoV-2 virus and human RNase P (internal control) were reverse transcribed (RT) and amplified by loop-mediated isothermal amplification (LAMP). The amplified products were detected by a Cas12a-based trans-cleavage reaction that generated a fluorescent signal which could be easily visualized by naked eye. Detection of internal control, RNase P gene was improved and optimized by redesigning RT-LAMP primers. A number of steps were reduced by combining the reagents related to the detection of Cas12a trans-cleavage reaction into a single ready-to-use mix. A portable, cost-effective battery-operated instrument, CRISPR-CUBE was developed to run the assay and visualize the outcome. The method and instrument were validated using both contrived and patient samples. CONCLUSIONS: The simplified CRISPR-based SARS-CoV-2 detection and instrument developed in this study, along with improved design for internal control detection allows for easier, more definitive viral detection requiring only reagents, consumables and the battery operable CRISPR-CUBE. SIGNIFICANCE AND IMPACT OF STUDY: Significant improvement in Cas12 method, coupled with simple visualization of end point makes the method and instrument deployable at the point-of-care (POC) for SARS-CoV-2 detection, without any recurrent cost for the lateral flow strips which is used in other POC methods.

Recent advances and applications of polymeric materials in healthcare sector and COVID-19 management.

The coronavirus disease pandemic is considered at its worst and all nations are collectively fighting to improve global public health. In this outlook, polymers and their related materials (including plastics) are the primary sources in the manufacturing of medical and personal protective equipment. Plastics can be mass-produced, economical, and sterilized, which makes them an inevitable material in the medical and healthcare sector. Along with plastics, antibacterial and antiviral coatings, polymeric nanomaterials and nanocomposites, and functional polymers have become excellent materials for COIVD-19. This review centres on the applications of polymer materials in managing the COVID-19 outbreak. Moreover, the utilization of plastics with its healthcare applications are reviewed. Apart from this, major challenges and future directions of these materials have also been discussed. This review will help aspiring researchers to develop the basic understanding of polymeric materials currently employed in medical sector.

Impact of Novel Covid-19 on Various Sectors: A Study

The COVID-19 pandemic, which originated in the city of Wuhan, China, has rapidly spread to various countries, and numerous cases have been reported worldwide. The outburst of coronavirus disease brought physical, economic and social life to a standstill. Approximately 32.4 million cases of coronavirus were reported in 2021, of which India has recorded 0.434 million deaths as on August 22, 2021. The virus is transmitted by inhalation or contact with infected droplets having incubation period from 2 to 14 days. The symptoms are typically fever, fatigue, sore throat, cough, shortness of breath, malaise among others. Overall, COVID-19 pandemic had a massive impact on the distinct sectors. Hence, in this paper the focus is on evaluating the impact of COVID-19 on distinct sectors, such as banking, health, economy, education, social, gold industries, IT industries, oil industries, manufacturing industries, and hotel and tourism sector.

Minnesota COVID-19 Lockdowns: The Effect on Acute Myocardial Infarctions and Revascularizations in the Community.

OBJECTIVE: To study associations between the Minnesota coronavirus disease 2019 (COVID-19) mitigation strategies on incidence rates of acute myocardial infarction (MI) or revascularization among residents of Southeast Minnesota. METHODS: Using the Rochester Epidemiology Project, all adult residents of a nine-county region of Southeast Minnesota who had an incident MI or revascularization between January 1, 2015, and December 31, 2020, were identified. Events were defined as primary in-patient diagnosis of MI or undergoing revascularization. We estimated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) stratified by key factors, comparing 2020 to 2015-2019. We also calculated IRRs by periods corresponding to Minnesota's COVID-19 mitigation timeline: "Pre-lockdown" (January 1-March 11, 2020), "First lockdown" (March 12-May 31, 2020), "Between lockdowns" (June 1-November 20, 2020), and "Second lockdown" (November 21-December 31, 2020). RESULTS: The incidence rate in 2020 was 32% lower than in 2015-2019 (24 vs 36 events/100,000 person-months; IRR, 0.68; 95% CI, 0.62-0.74). Incidence rates were lower in 2020 versus 2015-2019 during the first lockdown (IRR, 0.54; 95% CI, 0.44-0.66), in between lockdowns (IRR, 0.70; 95% CI, 0.61-0.79), and during the second lockdown (IRR, 0.54; 95% CI, 0.41-0.72). April had the lowest IRR (IRR 0.48; 95% CI, 0.34-0.68), followed by August (IRR, 0.55; 95% CI, 0.40-0.76) and December (IRR, 0.56; 95% CI, 0.41-0.77). Similar declines were observed across sex and all age groups, and in both urban and rural residents. CONCLUSION: Mitigation measures for COVID-19 were associated with a reduction in hospitalizations for acute MI and revascularization in Southeast Minnesota. The reduction was most pronounced during the lockdown periods but persisted between lockdowns.

Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.

Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants.

Since the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to > 233 million infections and > 4.7 million deaths as of Sept. 28th, 2021. SARS-CoV-2, Spike (S) protein binds to host cells by recognizing human angiotensin-converting enzyme 2 (hACE2) receptor. The viral S protein contains S1 and S2 domains that constitute the binding and fusion machinery, respectively. Structural analysis of viral S protein reveals that the virus undergoes conformational flexibility and dynamicity to interact with the hACE2 receptor. The SARS-CoV-2 variants and mutations might be associated with affecting the conformational plasticity of S protein, potentially linked to its altered affinity, infectivity, and immunogenicity. This review focuses on the current circulating variants of SARS-CoV-2 and the structure-function analysis of key S protein mutations linked with increased affinity, higher infectivity, enhanced transmission rates, and immune escape against this infection.

Immunizations with diverse sarbecovirus receptor binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability

Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Burnett et al. immunized humanized mice with different diverse sarbecovirus RBDs to elicit antibodies targeting conserved sites. Non-neutralizing cross-reactive antibodies targeting the conserved class 4 epitope were readily elicited. Neutralizing ability was reserved only for antibodies binding this conserved supersite through an elongated CDRH3 that obstructed ACE2-RBD interactions.

Overcoming challenges in implementing measures across multiple centers of a chain of hospitals to combat COVID-19 pandemic.

PURPOSE: Coronavirus outbreak was first reported towards the end of 2019 and has now been declared a pandemic by the World Health Organization. Post declaration, India announced lockdown and various guidelines were issued by Health authorities worldwide for the organizations to function in this emergency aeon. Different organizations strategized differently to respond to COVID 19 pandemic. The aim was to implement COVID 19 guidelines across all the centres of a chain of Eye hospitals in India in short span of time overcoming the challenges. METHODS: A SMART strategy was confabulated within the team. There were numerous challenges like lack of time, rapidly changing guidelines, no travelling scenarios, training and educating the staff in huge numbers, rapidly evolving situation, change management, need of increased vigilance, and language barrier at certain centres, sustaining quality assurance and motivating the staff in stressful times. The challenges were surpassed using a power packed strategy, dedicated efforts and team work grasping the available tools and technology from a single location. This template can serve us and other hospitals to respond in a better way for similar future challenges. RESULTS: The COVID 19 protocols were implemented across all the centres successfully. The entire Quality assurance system drifted to online platform and education and awareness methods took the digital thread. Teamwork synergized with the aforementioned things and we came out with flying colours achieving the goals in short span of time overcoming all the barriers. CONCLUSION: Difficult times bring challenges and challenges teach us the innovative ways to convert them into opportunities. A well planned strategy, best utilization of available resources, team work and continuous monitoring can bring the best outcomes forward.

Risk factors and protective measures for healthcare worker infection during highly infectious viral respiratory epidemics: A systematic review and meta-analysis.

OBJECTIVE: To investigate risk factors for healthcare worker (HCW) infection in viral respiratory pandemics: severe acute respiratory coronavirus virus 2 (SARS-CoV-2), Middle East respiratory syndrome (MERS), SARS CoV-1, influenza A H1N1, influenza H5N1. To improve understanding of HCW risk management amid the COVID-19 pandemic. DESIGN: Systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from conception until July 2020 for studies comparing infected HCWs (cases) and noninfected HCWs (controls) and risk factors for infection. Outcomes included HCW types, infection prevention practices, and medical procedures. Pooled effect estimates with pathogen-specific stratified meta-analysis and inverse variance meta-regression analysis were completed. We used the GRADE framework to rate certainty of evidence. (PROSPERO no. CRD42020176232, 6 April 2020.). RESULTS: In total, 54 comparative studies were included (n = 191,004 HCWs). Compared to nonfrontline HCWs, frontline HCWs were at increased infection risk (OR, 1.66; 95% CI, 1.24-2.22), and the risk was greater for HCWs involved in endotracheal intubations (risk difference, 35.2%; 95% CI, 21.4-47.9). Use of gloves, gown, surgical mask, N95 respirator, face protection, and infection training were each strongly protective against infection. Meta-regression showed reduced infection risk in frontline HCWs working in facilities with infection designated wards (OR, -1.04; 95% CI, -1.53 to -0.33, P = .004) and performing aerosol-generating medical procedures in designated centers (OR, -1.30; 95% CI, -2.52 to -0.08; P = .037). CONCLUSIONS: During highly infectious respiratory pandemics, widely available protective measures such as use of gloves, gowns, and face masks are strongly protective against infection and should be instituted, preferably in dedicated settings, to protect frontline HCW during waves of respiratory virus pandemics.

A new normal with cataract surgery during COVID-19 pandemic.

Cataract is the second leading cause of preventable blindness on the globe. Several programs across the country have been running efficiently to increase the cataract surgical rates and decrease blindness due to cataract. The current COVID-19 pandemic has led to a complete halt of these programs and thus accumulating all the elective cataract procedures. At present with the better understanding of the safety precautions among the health care workers and general population the Government of India (GoI) has given clearance for functioning of eye care facilities. In order to facilitate smooth functioning of every clinic, in this paper, we prepared preferred practice pattern based on consensus discussions between leading ophthalmologists in India including representatives from major governmental and private institutions as well as the All India Ophthalmological Society leadership. These guidelines will be applicable to all practice settings including tertiary institutions, corporate and group practices and individual eye clinics. The guidelines include triage, use of personal protective equipment, precautions to be taken in the OPD and operating room as well for elective cataract screening and surgery. These guidelines have been prepared based on current situation but are expected to evolve over a period of time based on the ongoing pandemic and guidelines from GoI.