Lipid-dependent assembly and budding of emerging viral pathogens

Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Lipid-enveloped viruses include dangerous pathogens such as coronaviruses (SARSCoV-2, etc.), filoviruses (Ebola virus and Marburg virus) and paramyxoviruses (Nipah virus, Hendra virus, etc.). Despite understanding some of the basics of how these viruses cause disease and enter host cells, not much is known on how these dangerous pathogens interact with host cell lipids to achieve new virion formation. The viral matrix or membrane protein regulates assembly and budding from the host cell membrane, connecting the viral lipid envelope to the viral nucleocapsid. Depending on the virus family, this assembly and budding may occur at the plasma membrane or the ER-Golgi intermediate compartment. This presentation will detail the biophysical and biochemical basis of how these emerging pathogens hijack host lipid membrane and metabolic networks to form new virus particles that undergo release from the host cell. These studies were funded in part by the National Institute of Allergy and Infectious Diseases (R01AI081077, AI158220, AI169896).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Safety Monitoring of Covid-19 Vaccine: In a Tertiary Care Hospital in Haryana

Objective: The present study aimed to ensure the safety and related potential adverse effects following ChAdOx1 nCoV-19 vaccination (AZD1222) in a scenario when numerous vaccines have been approved on an emergency basis by the WHO and other regulatory agencies to prevent the widespread of COVID-19 infection and to decrease the associated mortality and morbidity. Method(s): This study was an open, non-comparative, non-interventional, observational study conducted on healthcare workers of BPS Govt. medical college for women and elderly people who received the first dose of COVID-19 vaccinationChAdOx1 nCoV-19 vaccine (AZD1222) by conducting their interviews and recording the data Results: Between January and March 2021, a total of 1907 participants were enrolled in this study. Out of 1907 recipients, 70 recipients reports adverse drug events following vaccination. Myalgia (0.629%), headache (1.31%), fever >=(37.5 degreeC, 0.839%) and fever with chills (>= 37.5 degreeC, 1.048) were the most common adverse events after the first dose of vaccination of ChAdOx1 nCoV-19 vaccine (AZD1222. Throat irritation (0.209 %) and Generalised itching (0.262) were the least common adverse events. Conclusion(s): ChAdOx1 nCoV-19 (Astrazeneca) has an acceptable safety profile as observed in this study. To our knowledge, very few studies are done that review the safety of COVID-19 vaccines. Further safety data from a larger sample size and of longer duration are warranted to establish safetyCopyright © 2023 Innovare Academics Sciences Pvt. Ltd. All rights reserved.

Immunological examination of patients with rheumatological involvement after Covid-19 infection

Background: The emergence of autoinflammatory/autoimmune disorders in COVID-19 patients has necessitated the development of new strategies for the management of these phenomena. Several viruses have been shown to cause autoimmunity by boosting the production of autoreactive lymphocytes, resulting in a lack of tolerance in the host's immune response. The SARS-CoV- 2 virus and/or its proteins can cause autoimmunity by molecular mimicry, superantigen activity, and disruption of type I IFN production. Method(s): The data of three patients who applied to the outpatient clinics of pediatric immunology and rheumatology at Uludag University Hospital between March 2020 and December 2021 and were followed up with autoimmune/autoinflammatory disease following CCovid-19- 19 infection were analyzed retrospectively. Result(s): All patients were female and aged between 2-17 years. They had SARS-COV- 2 infection which was mild a few months ago. Before the Covid-19 infection, all of the patients were in good health. The patients had no history of frequent infections or familial predisposition to rheumatic diseases. Following the Covid-19- infection, all of our patients showed fever, rash, joint discomfort, and muscle soreness. Despite the fact that myalgia affects the whole body, arthralgia was present on the wrists and knees of patients. CRP, sedimentation rate, and acute phase reactants increased in all of them. According to the American College of Rheumatology's diagnostic criteria, our first patient was diagnosed with systemic lupus erythematosus (SLE) and was treated with hydroxychloroquine, intravenous immunoglobulin treatment and anakinra. Two of three were diagnosed with systemic juvenile idiopathic arthritis (sJIA) according to the League of Associations for Rheumatology (ILAR) criteria. Only one patient had low IgG and IgA levels (Table 1). Two patients showed a decrease in CD19+ naive cells percent and numbers. Conclusion(s): Following SARS-CoV- 2 infection, autoimmune and autoinflammatory disorders such as rheumatoid arthritis, psoriatic arthritis, type 1 diabetes and Still disease have been documented in adult cases. There are limited pediatric cases on this issue. It has been suggested that the persistence of the latent immune response after COVID-19 infection happens by sensitizing the immune system to viral particles long after they have been eliminated from organisms. Is the autoimmune process the effect of a viral infection or mis-targeted immune system? These questions need deep research and discussion.

COVID-19 and gastrointestinal endoscopy-proper strategies related to pandemic changes.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 was associated with new challenges in many fields of medicine. Preventing transmission of the virus and infection of professional healthcare workers became of major concern in our daily clinical practice during the pandemic. Viral particles within aerosols can be detected up to 3h after aerosolization. Recent work defined endoscopic procedures of the upper gastrointestinal tract as being aerosol-generating procedures (AGPs);thus, they can carry the possibility of transmitting airborne viruses to personnel. Because severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is primarily transmitted by aerosols and/or droplets, the use of personal protective equipment (PPE) is warranted. Guideline recommendations from the WHO and other societies were also modified early to include PPE as an infection prevention measure. The strict use of PPE has proven to be an effective prevention strategy over the 3 years since its implementation. With the introduction of vaccinations against SARS-CoV-2, increasing immunization of the population, and a changing pandemic infection pattern, the requirements for endoscopic departments in hospitals and outpatient care settings continued to change. In the postpandemic situation, there are only minor restrictions that affect the new "postpandemic reality", thus, allowing endoscopic services to be performed without major restrictions. Here, we present a review of recent and most relevant knowledge to summarize the prophylactic measures that must be taken to perform endoscopy under safe conditions during the COVID-19 pandemic.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

COVID-19 Pandemic: An Overview of its Origin, Current Status, and Ongoing Clinical Trials

The COVID-19 pandemic is raging across the globe, with the total active cases increas-ing each day. Globally over 63 million COVID-19cases and more than 1.4 million deaths have been reported to WHO. Throughout the world, academicians, clinicians and scientists are working tirelessly on developing a treatment to combat this pandemic. The origin of novel SARS-CoV-2 virus still remains foggy but is believed to have originated from a bat coronavirus RaTG13 with which it shares approximately 96% sequence similarity. In the present review, the authors have pro-vided an overview of the COVID-19 pandemic, epidemiology, transmission, developments related to diagnosis, drugs and vaccines, along with the genetic diversity and lifecycle of the SARS-CoV-2 based on the current studies and information available.Copyright © 2022 Bentham Science Publishers.

Virucidal efficacy of household dishwashers

Not only since SARS-CoV-2, have transmission routes of viruses been of interest. Noroviruses e.g., can be transmitted via smear infection, are relatively stable in the environment and very resistant to chemical disinfection. Some studies determined the virucidal efficacy of laundering processes, but few studies focused on the virucidal efficacy of dishwashing processes. Here, especially consumer related conditions are of interest. Households for example are a hotspot of norovirus infection and thus a sufficient reduction of these and other viruses from dishes must be insured to avoid an infection via this route. The likelihood of such an event should not be underestimated, since it was shown that the washing machine can be a reservoir for the transmission of extended spectrum beta-lactamase producing bacteria in newborns. Although viruses do not replicate in these devices a transmission via contaminated cutlery e.g., cannot be excluded. Using a consumer related approach to determine the virucidal efficacy of dishwashers, we found a combination of a bleach containing dishwasher detergent, a cleaning temperature of 45 C for 45 min and a rinsing temperature of 50 C, to be sufficient to reduces viral titer of bovine corona virus, murine norovirus and modified vaccinia virus by 4.8, 4.2 and 3.8 logarithmic stages respectively.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

mRNA vaccine boosts the SARS-CoV-2 specific mucosal antibody in recipients of inactivated and mRNA vaccines

Background: Little is known about the induction of mucosal Ab after the 3rd dose. We reported that two doses of BNT162b2 induced mucosal Abs as early as 14-days after the 1st dose. As BNT162b2 only provides the RNA encoding a full-length spike (S) protein, a mixed-vaccine regime with a vaccine that provides inactivated but intact viral particles was executed in some countries to expand the diversity of SARS-CoV-2 Abs. Aim and objectives: To examine the mucosal and plasma Ab induction in vaccine recipients receiving their 3rd vaccine dose with single or mixed vaccine type. Method(s): 46 healthy subjects who had BNT162b2 (B) or CoronaVac (C) in a sequence of either BBB, BBC, CCC or CCB were recruited for a longitudinal sampling of nasal fluid and blood. The S1-specific Ab and neutralizing Ab against SARS-CoV-2 VOCs were measured. Result(s): All BBB recipients (n=28) had nasal specific S1-IgA and IgG after two doses, and the Abs lasted six months and were readily induced after the 3rd dose. In BBC recipients (n=4), though they had prior induction of nasal Abs after two doses of B, the inactivated vaccine did not boost their nasal Abs. In CCC recipients (n=5), there was no induction on nasal Abs. If they adopted the CCB regime (CCB, n=11), they acquired nasal Ab after the 3rd dose. The nasal neutralizing antibodies against the wild type were boosted in 20/28 of the BBB recipients and induced in 8/11 of the CCB recipients but not in CCC or BBC recipients. Lastly, all 46 subjects had a boosted specific S1-IgA and S1IgG in plasma. Conclusion(s): Our findings highlighted the uniqueness of BNT162b2 in induing nasal Ab regardless of the vaccination history.

Predictive indexes in prolonged weaning of mechanical ventilation due to tracheostomy in patients with COVID19 pneumonia

Introduction: In the pandemic, porlonged weaning(PW) of mechanical ventilation (wMV) of COVID patients in the intermediate respiratory care unit IRCU was performed. It was necessary to use predictive indexes for(wMV), which do not generate aerosolization of viral particles. Objetive: To develop a oredictive indexes for wMV and tracheostomy decannulation (TCHd) for COVID-19 pneumonia in IRCU. Method(s): The sample consists of 76 serial cases to the IRCU, in 2020 and 2021. Indexes were developed with an oxygenation variable (PaO2/FiO2) or (SatO2/FiO2), respiratory rate (RR) and corrected (C) in based alveolar ventilation (PCO2), the following indexes were developed as predictors of wMV;ventilation-oxygenation index IVOX= (PaFi/RR), IVOX corrected for PCO2 is IVOX-C=(IVOX x Oco2) and with SaFi the SIVOX-C= [(SaFi/RR) x PCO2]. The StatPlus 7.3 program forWindows was used of the Mann-Whitney U (M-WU) comparing their mean values, using binary logistic regression (BLR) and area under curve AUC ROC to compare their predictability. Result(s): Mean age 58,9 +/-14,4;male 53,7% and the stay in the IRCU was 16,7+/- 11 days, mortality of 28,3%(22);received MV (71,0%) 54. wMV was(70,4%)38 and TCHd was (67,3)35. The mean differrences in disconnected and non-diconnected from MV analyzed by M-WU are significante. An BLR model was built to analyze the predictive behavior ofIVOX, IVOX-C and SIVOX-C for wMV. It was observed that the three indexes are predictive, but IVOX-C and SIVOX-C have the highest predictive weight. In turn the AUC ROC was significance. Conclusion(s): The construction of a predictive indexes of wMV and TCHd in this sample the patients who reached the objective.

Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Fragranced hand gels: beware the risk of contact allergy

An 11-year-old boy presented to the children's Emergency Department in Autumn 2020 with acute blistering of his palms. No other parts of the body or mucosal surfaces were involved. He was systemically well, with no significant past medical history except for eczema in early childhood. He had recently started back at school and was using hand gel regularly as part of precautions to reduce SARS-CoV-2 (COVID-19) transmission during the pandemic. There had been no other contact with chemicals, plants, crafting materials, glues, paints or homemade slime. Clinical photographs showed swelling and large bullae on the thenar eminence and lateral fingers. There was no erythema, nail involvement or significant scaling. The clinical diagnosis was acute pompholyx that was either irritant or allergic in origin. Testing to the standard series showed inconclusive results to some fragrances in the standard series. The patch testing to fragrance in the standard series was repeated and the fragrance series was added. The repeat test confirmed allergic contact dermatitis to fragrance with a positive to Myroxylon pereirae, linalool, limonene, sandalwood oil and majantol. The hand gels were found to contain linalool and limonene. To curb the spread of COVID-19, regular handwashing and the use of alcohol-based hand sanitizers/gels are part of everyday hygiene guidance for the general public. Therefore, the incidence of hand dermatitis is likely to rise. The World Health Organization and the Food and Drugs Administration advise that a minimum alcohol content of 60% is required to inactivate viral particles;however, it is also important to be aware that hand sanitizers/gels may also contain other constituents, including thickeners, humectants (e.g. propylene glycol) and fragrance. Research into the ingredients of 10 widely used hand sanitizers recently investigated by an independent watchdog for their alcohol content found that six had their ingredients listed online and five contained fragrance. The patient responded to topical treatment with a superpotent topical steroid cream (Dermovate) twice daily, white soft paraffin 50 : 50, an antiseptic emollient (Dermol 500) to wash the hands and allergen avoidance. We highlight to other dermatologists that contact allergy to fragrance or other components in hand sanitizer/gels may present acutely with pompholyx and to consider testing to the standard and fragrance series if this is suspected.

Detection of SARS-CoV-2 in Follicular and Endocervical Fluid of in Vitro Fertilization Candidates with Positive Polymerase Chain Reaction Tests

Background: The coronavirus disease 2019 (COVID-19) pandemic was a unique global challenge with a wide range of severity extending from an asymptomatic form to a serious intense respiratory syndrome. This study aimed to detect SARS-CoV-2 in the follicular and endocervical fluid of in vitro fertilization (IVF) candidate patients with a positive polymerase chain reaction (PCR) test for SARS-CoV-2. Method(s): All participants and their partners, who were a candidate to start assisted reproductive technology (ART) from April 2020 to October 2020, completed a triage questionnaire two weeks before starting the ART cycle. According to Avicenna center protocol, a diagnostic test for COVID-19 using real-time PCR of nasopharyngeal swabs was performed on all ART candidates, 48 hours before the day of the oocyte trigger. In the operating room, sterile swabs were used to provide cervicovaginal specimens to determine SARS-CoV-2 in cervicovaginal fluid. Moreover, the first aspirated follicular fluid was referred to the lab to assess the presence of SARS-CoV-2. Result(s): A positive PCR test for SARS-CoV-2 was verified in 32 participants. In this study, virus particles were not detected in the follicular and endocervical fluid of the women with positive PCR tests. Conclusion(s): We are still at the beginning of the road and need reliable data on the safety of ART at the time of the pandemic. The risk of infection during all processes of ART including oocyte retrieval needs attention. The fluid from mature follicles is a potential site to be infected and the human cumulus cells could not be a deterrent factor to the entrance of the virus in the oocyte. This process may lead to gametes infection. We did not detect virus RNA in the follicular and endocervical fluid of the patients with a positive PCR test. Although, more studies with a larger sample size are mandatory in this field.

ROLE OF IFNgamma IN PATHOGENESIS OF SARS-CoV-2 INFECTION.

To date, there is no consensus explaining the relationship between varying concentrations of IFNgamma and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNgamma in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNgamma which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNgamma activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNgamma exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNgamma concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNgamma and COVID-19 severity. In a number of studies, the significantly high levels of IFNgamma in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNgamma concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNgamma concentrations in convalescent patients, the mechanism of antagonism between IFNgamma and IL-4 is considered, where the decreases serum concentrations of IFNgamma along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNgamma are at reduced risk for severe course of COVID-19. Copyright © 2022, SPb RAACI.

Visualization of SARS-CoV-2 particles in naso/oropharyngeal swabs by thin section electron microscopy.

BACKGROUND: SARS-CoV-2 replicates efficiently in the upper airways of humans and produces high loads of virus RNA and, at least in the initial phase after infection, many infectious virus particles. Studying virus ultrastructure, such as particle integrity or presence of spike proteins, and effects on their host cells in patient samples is important to understand the pathogenicity of SARS-CoV-2. METHODS: Suspensions from swab samples with a high load of virus RNA (Ct < 20) were sedimented by desktop ultracentrifugation and prepared for thin section electron microscopy using a novel method which is described in detail. Embedding was performed in Epon or in LR White resin using standard or rapid protocols. Thin sections were examined using transmission electron microscopy. RESULTS: Virus particles could be regularly detected in the extracellular space, embedded in a background of heterogenous material (e.g. vesicles and needle-like crystals), and within ciliated cells. Morphology (i.e. shape, size, spike density) of virus particles in the swab samples was very similar to particle morphology in cell culture. However, in some of the samples the virus particles hardly revealed spikes. Infected ciliated cells occasionally showed replication organelles, such as double-membrane vesicles. The most common cells in all samples were keratinocytes from the mucosa and bacteria. CONCLUSIONS: The new method allows the ultrastructural visualization and analysis of coronavirus particles and of infected host cells from easy to collect naso/oropharyngeal patient swab samples.

Phage-Derived Oncolytic Viruses with 3C from Seneca Valley Virus for Targeted Therapy of Cervical Cancer

Cancer gene therapy based on various gene delivery vectors has some potential but also has obvious disadvantages. In this study, a new M13 phage-based oncolytic virus is constructed that carried the RGD peptides to target tumor cells and the 3C gene of Seneca Valley virus (SVV) preceded by a eukaryotic initial transcriptional region (ITR) to transcribe an oncolytic protein to kill tumor cells. Recombinant virus particles of 1200 nm in length are obtained in large quantities by transfecting the recombinant M13 phage plasmid into the host BL2738 and are investigated in vitro in tumor cells and in vivo in tumor-bearing mice to evaluate their antitumor effect. The experiments using Hela cells confirm that the engineered M13 phage can target and enter Hela cells, and express the SVV 3C protein, resulting in apoptosis of target cells by upregulating the expression of caspase 3. Furthermore, the results of experiments in vivo also show that the recombinant phage significantly inhibits the enhanced tumor volume in nude mice compared to the control groups. The M13 phage may be engineered to fuse with a variety of oncolytic proteins to inhibit the growth of tumor cells in the future, providing a promising phage-based targeted oncolytic reagent.

A Randomized-controlled Simulation based Pilot Trial of Patient Barrier Devices on Resuscitation Quality for Patients Under Investigation for COVID-19

Background: The COVID-19 pandemic had placed constraints on cardiopulmonary resuscitation (CPR), including early intubation, minimizing bag-valve mask ventilation1, and using protective equipment and barriers during resuscitation. Patient barrier devices have been introduced in emergency departments and operating rooms, consisting of plastic drapes over the patient9, or the use of an acrylic box.2 Both of these adjuncts reduce aerosolization of oropharyngeal particles from the patient, and can facilitate video-based intubation.2,3 However, it is unknown whether these devices help or hinder the ultimate resuscitation quality in cardiopulmonary arrest patients. Our specific question addresses the effect of a patient barrier device and COVID-19 resuscitation recommendations on resuscitation quality. We hypothesize that a simple patient barrier consisting of a plastic drape reduces healthcare worker (HCW) contamination without affecting resuscitation quality. Methods: This was a single-center randomized controlled pilot trial, in which in-hospital teams of 4 to 6 HCWs were randomized to either use a plastic drape (intervention) or no plastic drape (control) for a simulated adolescent cardiopulmonary arrest. The manikin was modified to emanate simulated viral particles (GloGerm®, Moab, UT) from the trachea detectable using ultraviolet light. Teams managed a cardiopulmonary arrest until intubation, using Personal Protective Equipment (PPE) and PALS/ACLS algorithms. Data were captured via arbitrated video review. Resuscitation data included time-to-bagging, time-to-intubation, and chest compression quality metrics - depth, rate, and lean. Contamination data were collected visually, marking the number of PPE equipment with visible fluorescence. Mean NASA-TLX and NOTECHS scores measured workload and team performance. Descriptive and univariate statistics were used to determine differences between intervention and control teams. Results: Fifteen simulations were conducted from 2020 to 2021;one was excluded from analysis as a performance outlier, leaving 7 intervention vs. 7 control teams. Scenarios lasted an average of 10.4+/- 3 minutes. Time-to-bagging, time-to-intubation, and intubation duration were not different between groups (72.1+/-22.4 vs 56.7+/-30.9 sec, 536+/-289 vs 544+/-127 sec, 78.9+/-73.0 vs 95.7+/-113 sec, p>0.3), and CPR quality for mean depth, rate, and lean were also not different (36.1+/-11.6 vs 30.9+/-13.2 cm, 108+/-13 vs 112+/-8/min, 8.7+/-5.2 vs 4.5+/-4.3 cm, p>0.14). Contamination rates were lower for the intubating physician (2.3+/-0.5 vs 4.1+/-0.9 surfaces, p<0.001) and for all participants (2.8+/-0.7 vs 3.7+/-0.9 surfaces, p=0.05) when using a barrier. No other contamination rate changes were observed. Participants noted no differences in team performance (22.4+/-1.6 vs 20.8+/-1.8, p=0.5) but a slight trend towards higher workload with the plastic barrier (+9.5+/-7.7 vs -0.1+/-11.5, p=0.09). Conclusion: The use of a plastic drape as a patient barrier appears to reduce simulated virus contamination for HCWs, particularly for the intubation physician during a simulated cardiopulmonary arrest without affecting resuscitation performance. Perceived workload increases with the drape, and further studies are needed to substantiate these findings in larger samples and in different settings.

LONGITUDINAL CLINICAL TRAITS OF HEART FAILURE PATIENTS READMITTED POST COVID-19 INDEX HOSPITALIZATION

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARSCoV- 2) has substantial morbidity and mortality in patients with heart failure (HF). Hospital mortality exceeds 30% in the American Heart Association's COVID-19 Cardiovascular Disease registry. We characterized clinical traits associated with progression to critical illness (PCI, ICU admission or hospital death) during index and subsequent hospitalizations in SARS-CoV-2 infected patients with extant HF. METHODS: Electronic health records underwent extraction of demographics, anthropometrics, vital signs, laboratory tests, and ICD-10-CM-based Elixhauser comorbidity categories. Univariate logistic regression was used to identify features associated with PCI. Continuous data summarized with median [IQR] were compared using Kruskal-Wallis test and discrete data with chi-squared test. Confounders statistically balanced included age, sex, race, COVID-19 directed treatment, and 4-waves of pandemic. RESULTS: Among HF patients admitted between March 14, 2020 and September 30, 2021, 530 underwent index COVID-19 hospitalization. Among those, 111 were readmitted once, and 43 readmitted at least twice. Index admission median age was 75 [65-84] years, body mass index (BMI) 29.5 [24.9-35.3], and time to readmission 247.7 [44.7-784.1] days. Subsequent time to readmission was 34.7 [5.7-92] days. Most common admission comorbidities were hypertension (81%), diabetes (43%), renal failure (42%), obesity (38%), chronic pulmonary disease (36%), and deficiency anemia (32%). The most common comorbidities at second readmission were renal failure (60%), deficiency anemia (53%), diabetes (40%), and chronic pulmonary disease (40%). PCI occurred in 32% of index admissions, 21% of first readmissions, and 14% of second readmissions. Hospital death or discharge to hospice occurred in 28%, 18%, and 23% of readmissions respectively. CONCLUSIONS: Days to readmission declined revealing impact of inflammation and immunomodulation caused by SARS-CoV-2. Although hypertension was the most common comorbidity at index admission it was the least common at subsequent readmissions. This may represent improved control or death of those poorly controlled. Renal failure being the most common comorbidity at second readmission may represent worsening function due to SARS-CoV-2 infection and injury or worsening HF syndrome. Progressively worsening pBNP and hsTnI likely reflect direct myocyte injury by heightened entry of SARS-CoV-2 viral particle due to expression of angiotensinconverting enzyme 2. HF patients should be urged to undergo SARS-CoV-2 vaccination with apropos boost.