Strategic deactivation of mRNA COVID-19 vaccines: New applications for siRNA therapy and RIBOTACs.

The rapid development and authorization of messenger ribonucleic acid (mRNA) vaccines by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) in 2020 marked a significant milestone in human mRNA product application, overcoming previous obstacles such as mRNA instability and immunogenicity. This paper reviews the strategic modifications incorporated into these vaccines to enhance mRNA stability and translation efficiency, such as the inclusion of nucleoside modifications and optimized mRNA design elements including the 5' cap and poly(A) tail. We highlight emerging concerns regarding the wide systemic biodistribution of these mRNA vaccines leading to prolonged inflammatory responses and other safety concerns. The regulatory framework guiding the biodistribution studies is pivotal in assessing the safety profiles of new mRNA formulations in use today. The stability of mRNA vaccines, their pervasive distribution, and the longevity of the encapsulated mRNA along with unlimited production of the damaging and potentially lethal spike (S) protein call for strategies to mitigate potential adverse effects. Here, we explore the potential of small interfering RNA (siRNA) and ribonuclease targeting chimeras (RIBOTACs) as promising solutions to target, inactivate, and degrade residual and persistent vaccine mRNA, thereby potentially preventing uncontrolled S protein production and reducing toxicity. The targeted nature of siRNA and RIBOTACs allows for precise intervention, offering a path to prevent and mitigate adverse events of mRNA-based therapies. This review calls for further research into siRNA and RIBOTAC applications as antidotes and detoxication products for mRNA vaccine technology.

Wound Irrigation in the Prevention of Surgical Site Infection in Elective Colorectal Surgery: A Retrospective Cohort Study.

Background Surgical site infection in colon surgery is associated with significant cost and increased length of hospital stay. Recently, there has been interest in the use of pulsed lavage to reduce the risk of surgical site infection in contaminated wounds. Although increasingly used and gaining popularity, its effectiveness in elective colorectal surgery has been poorly documented. This study aimed to investigate the incidence of surgical site infection within 30 days of elective colorectal surgery in patients who underwent wound irrigation with pulse lavage versus standard closure. Methodology A retrospective study was conducted at a university hospital over a two-year period between January 2020 and December 2021. All adult patients who underwent elective colorectal surgery were eligible for inclusion. Results A total of 222 patients underwent elective colorectal surgery during the study period. Operative procedures included abdominoperineal resections, left and right hemicolectomies, pelvic exenterations, small bowel or large bowel resections, as well as stoma reversals, formations, and refashioning. In total, 76 patients underwent pulse lavage while 146 did not. The total number of surgical site infections was 39 during the study period. Infection rates in the pulse lavage group were 14.47% compared to 19.18% in the standard closure group. The chi-square analysis concluded the difference in infection rates was not statistically significant (p = 0.213). Conclusions The findings demonstrated a difference in infection rates of almost 5% favouring the pulse lavage group; however, it did not reach a statistical difference. Although infection rates were in keeping with those described in the literature, further studies in the form of randomized controlled trials should be performed to determine the benefits, if any, of pulse lavage in colorectal surgery.

Withdrawn: A systematic review of autopsy findings in deaths after COVID-19 vaccination.

This Article-in-Press has been withdrawn at the request of the Editors-in-Chief. Members of the scientific community raised concerns about this Article-in-Press following its posting online. The concerns encompassed. • Inappropriate citation of references. • Inappropriate design of methodology. • Errors, misrepresentation, and lack of factual support for the conclusions. • Failure to recognise and cite disconfirming evidence. The concerns were shared with the authors, who prepared a response and submitted a revised manuscript for consideration by the journal. In consideration of the extent of the concerns raised and the responses from the authors, the journal sent the revised manuscript to two independent peer-reviewers. The peer-reviewers concluded that the revised manuscript did not sufficiently address the concerns raised by the community and that it was not suitable for publication in the journal. The authors disagree with this withdrawal and dispute the grounds for it. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination.

According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS-CoV-2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS-CoV-2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1-methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex-diverse people. The translation of 1-methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off-target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18-flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ-related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)-enzymatic cleavage mechanisms known in chemistry.

Retraction: COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.

[This retracts the article DOI: 10.7759/cureus.52876.].

Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis.

COVID-19 vaccines have been linked to myocarditis, which, in some circumstances, can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-induced myocarditis through 3 July 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included. Causality in each case was assessed by three independent physicians with cardiac pathology experience and expertise. We initially identified 1691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In two cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome. The mean age of death was 44.4 years old. The mean and median number of days from last COVID-19 vaccination until death were 6.2 and 3 days, respectively. We established that all 28 deaths were most likely causally linked to COVID-19 vaccination by independent review of the clinical information presented in each paper. The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms, and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests that there is a high likelihood of a causal link between COVID-19 vaccines and death from myocarditis.

Determinants of COVID-19 vaccine-induced myocarditis.

Background: Following the roll-out of the Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen Ad26.COV2.S coronavirus disease 2019 (COVID-19) injections in the United States, millions of individuals have reported adverse events (AEs) using the vaccine adverse events reports system (VAERS). The objective of this analysis is to describe the myocarditis data in VAERS and the COVID-19 vaccines as potential determinants of myocarditis. Methods: We used VAERS data to examine the frequency of reporting myocarditis since the beginning of the mass vaccination campaign and compared this with historical values in VAERS and COVID-19 vaccine administration data from the Our World in Data database. We examined myocarditis reports in VAERS in the context of sex, age, and dose. Statistical analysis was done using the Student's t-test to determine statistically significant differences between ages among myocarditis adverse events (AEs) and the chi-square test to determine relationships between categorical variables with statistical significance. Results: We found the number of myocarditis reports in VAERS after COVID-19 vaccination in 2021 was 223 times higher than the average of all vaccines combined for the past 30 years. This represented a 2500% increase in the absolute number of reports in the first year of the campaign when comparing historical values prior to 2021. Demographic data revealed that myocarditis occurred most in youths (50%) and males (69%). A total of 76% of cases resulted in emergency care and hospitalization. Of the total myocarditis reports, 92 individuals died (3%). Myocarditis was more likely after dose 2 (p < 0.00001) and individuals less than 30 years of age were more likely than individuals older than 30 to acquire myocarditis (p < 0.00001). Conclusion: COVID-19 vaccination is strongly associated with a serious adverse safety signal of myocarditis, particularly in children and young adults resulting in hospitalization and death. Further investigation into the underlying mechanisms of COVID-19 vaccine-induced myocarditis is imperative to create effective mitigation strategies and ensure the safety of COVID-19 vaccination programs across populations.

Using VAERS to understand myocarditis associated with COVID-19 vaccination Why was the study done? Heart inflammation, known as myocarditis, has been previously associated with COVID-19 vaccination. After the Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccines were given in the United States, millions of people reported side effects, including myocarditis, using a system called the Vaccine Adverse Event Reporting System (VAERS). Therefore, the researchers sought to further investigate possible links between COVID-19 vaccination and myocarditis using VAERS. What did the researchers do? The researchers used VAERS to check the frequency of myocarditis reports after COVID-19 vaccination and compared this with past reports from other vaccines over the years. They also studied details such as the age and gender of those affected, and which dose of the vaccine they had received. What did the researchers find? In 2021, there was a dramatic increase in the number of myocarditis reports linked to the COVID-19 vaccine, far higher than the reports from all other vaccines combined over the previous 30 years. This side effect was mostly reported in young individuals, especially males. Most of those who reported myocarditis needed emergency medical care or had to be hospitalized. Out of those affected, 92 individuals died. Myocarditis was more likely following a second dose of vaccine. Furthermore, individuals under the age of 30 were more prone to acquire myocarditis from COVID-19 vaccination compared to those aged 30 and above. What do the findings mean? The researchers found a strong link between COVID-19 vaccination and myocarditis, especially in kids and young adults. This can lead to hospital stays and, in some cases, death. We need to study more about how the COVID-19 vaccine might cause heart inflammation to find ways to prevent it and make sure the vaccine is safe for continued use in all age groups.

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

Bell's palsy or an aggressive infiltrating basaloid carcinoma post-mRNA vaccination for COVID-19? A case report and review of the literature.

We report on an aggressive, infiltrating, metastatic, and ultimately lethal basaloid type of carcinoma arising shortly after an mRNA vaccination for COVID-19. The wife of the patient, since deceased, gave the consent for publishing the case. The malignancy was of cutaneous origin and the case showed symptoms consistent with Bell's palsy and trigeminal neuralgia beginning four days post-vaccination (right side head temporal pain). The temporal pain was suggestive for inflammation and impairment of T cell immune activation. Magnetic Resonance Imaging (MRI) showed a vascular loop on the left lateral aspect of the 5th cranial root exit of cerebellopontine angle constituting presumably a normal variant and was considered as an unrelated factor to the right-sided palsy and pain symptoms that corresponded to cranial nerves V (trigeminal nerve) and VII (facial nerve). In this study we describe all aspects of this case and discuss possible causal links between the rapid emergence of this metastatic cancer and mRNA vaccination. We place this within the context of multiple immune impairments potentially related to the mRNA injections that would be expected to potentiate more aggressive presentation and progression of cancer. The type of malignancy we describe suggests a population risk for occurrence of a large variety of relatively common basaloid phenotype cancer cells, which may have the potential for metastatic disease. This can be avoidable with early diagnosis and adequate treatment. Since facial paralysis/pain is one of the more common adverse neurological events following mRNA injection, careful inspection of cutaneous/soft tissue should be conducted to rule out malignancy. An extensive literature review is carried out, in order to elucidate the toxicity of mRNA vaccination that may have led to the death of this patient. Preventive and precise routine clinical investigations can potentially avoid future mortalities. See also Figure 1(Fig. 1).

Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination.

The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.

Outcomes after early treatment with hydroxychloroquine and azithromycin: An analysis of a database of 30,423 COVID-19 patients.

Background: Many studies have evaluated the use of hydroxychloroquine in COVID-19. Most retrospective observational studies demonstrate a benefit of using HCQ on mortality, but not most randomized clinical trials. Methods: We analyzed raw data collected from a cohort of 30,423 patients with COVID-19 cared for at IHU Méditerranée Infection in Marseille France and extracted from the DRYAD open data platform. We performed univariate and multivariable logistic regressions with all-cause mortality within six weeks. Multivariable logistic regressions were adjusted for sex, age group (<50, 50-69, 70-89 and â€‹> â€‹89 years), periods (or variants), and type of patient management. Results: Among 30,202 patients for whom information on treatment was available, 191/23,172 (0.82%) patients treated with HCQ-AZ died, compared to 344/7030 (4.89%) who did not receive treatment with HCQ-AZ. HCQ-AZ therapy was associated with a lower mortality than treatment without HCQ-AZ (odds ratio (OR) 0.16; 95% confidence interval (CI), 0.14-0.19). After adjustment for sex, age, period, and patient management, HCQ-AZ was associated with a significantly lower mortality rate (adjusted OR (aOR) 0.55, 95% CI 0.45-0.68). On a subsample of 21,664 patients with available variant information, results remained robust after adjustment on sex, age, patient management and variant (aOR 0.55; 95% CI 0.44-0.69). On a subsample of 16,063 patients, HCQ-AZ was still associated with a significantly lower mortality rate (aOR 0.47, 95%CI 0.29-0.75) after adjustment for sex, age, period, patient management, vaccination status and comorbidities. Conclusion: Analysis of this large online database showed that HCQ-AZ was consistently associated with the lowest mortality.

Autoimmune inflammatory reactions triggered by the COVID-19 genetic vaccines in terminally differentiated tissues.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display a wide distribution within the body, affecting tissues that are terminally differentiated and far away from the injection site. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesises non-self antigens, inevitably becomes the target of the immune system, and since the human body is not a strictly compartmentalised system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities to the critical need for biodistribution studies for the genetic vaccines against COVID-19, as well as for rational harm-benefit assessments by age group.

Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO2TECT Randomized Clinical Trial of ESA-Treated Patients.

Rationale & Objective: In the PRO2TECT trials, vadadustat was found to be noninferior to darbepoetin alfa in hematologic efficacy but not for major adverse cardiovascular events (MACE; all-cause death or nonfatal myocardial infarction or stroke) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). We investigated the regional differences in MACE in the PRO2TECT trials. Study Design: Phase 3, global, open-label, randomized, active-controlled clinical trial. Setting & Participants: A total of 1,725 erythropoiesis-stimulating agent (ESA)-treated patients with anemia and NDD-CKD. Intervention: 1:1 randomization to receive vadadustat or darbepoetin alfa. Outcomes: The primary safety end point was the time to first MACE. Results: At baseline, patients in Europe (n=444) were primarily treated with darbepoetin alfa, showed higher proportions on low ESA doses (<90 U/kg/wk epoetin alfa equivalents) with a hemoglobin concentration of ≥10 g/dL compared with patients in the US (n=665) and non-US/non-Europe (n=614) regions. The MACE rates per 100 person-years in the 3 vadadustat groups across regions were 14.5 in the US, 11.6 in Europe, and 10.0 in the non-US/non-Europe groups, whereas event rates in the darbepoetin alfa group were considerably lower in Europe than in the US and non-US/non-Europe groups (6.7 vs 13.3 and 10.5, respectively). The overall hazard ratio for MACE for vadadustat vs darbepoetin alpha was 1.16; 95% CI, 0.93-1.45, but varied by geographical region, with a greater hazard ratio seen in Europe (US, 1.07; 95% CI, 0.78-1.46; Europe, 2.05; 95% CI, 1.24-3.39; non-US/non-Europe, 0.91; 95% CI, 0.60-1.37); interaction between study treatment and geographical region, P = 0.07). In Europe, ESA rescue was associated with a higher risk of MACE in both groups. Limitations: Several analyses are exploratory. Conclusions: In this trial, there was a low risk of MACE in the darbepoetin alfa group in Europe. Patients in Europe were generally on low doses of ESA, with hemoglobin already within target range. The low risk of MACE may have been related to a limited need to switch and titrate darbepoetin alfa compared with the non-US/non-Europe group. Funding: Akebia Therapeutics, Inc. Trial Registration: ClinicalTrials.gov identifier: NCT02680574.

Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO2TECT Randomized Clinical Trial of ESA-Naïve Patients.

Rationale & Objective: Prespecified analyses of the PRO2TECT trials comparing the safety of the oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) found no difference in major adverse cardiovascular events (MACE; death from any cause or nonfatal myocardial infarction or stroke) among US patients and a higher risk among patients treated with vadadustat outside the United States. We investigated regional differences in MACE in the PRO2TECT trial that enrolled 1,751 patients previously untreated with erythropoiesis-stimulating agents. Study Design: Phase 3, global, open-label, randomized, active-controlled clinical trial. Setting and Participants: Erythropoiesis-stimulating agent-untreated patients with anemia and NDD-CKD. Intervention: Eligible patients were randomized 1:1 to receive vadadustat or darbepoetin alfa. Outcomes: The primary safety end point was time to first MACE. Secondary safety end points included time to first expanded MACE (MACE plus hospitalization for heart failure or thromboembolic event, excluding vascular access thrombosis). Results: In the non-US/non-Europe region, there was a higher proportion of patients with baseline estimated glomerular filtration rate (eGFR) level of ≤10 mL/min/1.73 m2 in the vadadustat group [96 (34.7%)] than in the darbepoetin alfa group [66 (24.0%)]. In this region, there were 21 excess MACEs reported in the vadadustat group [78 events (n=276)] versus the darbepoetin alfa [57 events (n=275)], including 13 excess noncardiovascular deaths, largely from kidney failure. Noncardiovascular deaths were concentrated in Brazil and South Africa, which enrolled higher proportions of patients with an eGFR of ≤10 mL/min/1.73 m2 and who may not have had access to dialysis. Limitations: Different regional treatment patterns of patients with NDD-CKD. Conclusions: The higher MACE rate in the non-US/non-Europe vadadustat group may have been partly because of imbalances in the baseline eGFR level in countries where dialysis was not uniformly available resulting in many kidney-related deaths.

Beclometasone inhaler-induced recovery of refractory peri-ileostomy skin complications.

Peristomal skin complications (PSCs) are relatively common in ostomy patients, particularly in those with ileostomies. Non-healing irritation presents a clinical challenge and leads to pain and impaired quality of life for patients. METHODS: The cases of four ileostomy patients experiencing severe, challenging PSCs refractory to appliance changes, conventional dressings and barrier creams are discussed. FINDINGS: The cases of one male and one female patient with an end ileostomy post-subtotal colectomy for ulcerative colitis, one female with a defunctioning ileostomy post-anterior resection for sigmoid carcinoma and one male with an end ileostomy with a complex Crohn's surgical history are described. Two puffs of a 250 mcg metered dose beclometasone inhaler were applied to the affected skin once or twice daily. Treatment ranged from 6 to 21 days. Complete resolution was seen in all cases. CONCLUSION: Topical use of a beclometasone inhaler was effective for severe peri-ileostomy PSC secondary to four different aetiologies. Further studies are warranted to determine the effectiveness of this treatment in a larger patient cohort.

Acute COVID-19 Management in Heart Failure Patients: A Specific Setting Requiring Detailed Inpatient and Outpatient Hospital Care.

The relationship existing between heart failure (HF) and COVID-19 remains questioned and poorly elucidated. Many reports suggest that HF events are reduced during pandemics, although other studies have demonstrated higher mortality and sudden death in patients affected by HF. Several vascular, thrombotic, and respiratory features may deteriorate stable HF patients; therefore, the infection may directly cause direct myocardial damage, leading to cardiac function deterioration. Another concern is related to the possibility that antiviral, anti-inflammatory, and corticosteroid agents commonly employed during acute COVID-19 infection may have potentially deleterious effects on the cardiovascular (CV) system. For these reasons, HF patients deserve specific management with a tailored approach in order to avoid arrhythmic complications and fluid retention events. In this review, we describe the complex interplay between COVID-19 and HF, the evolving trend of infection with related CV events, and the specific management strategy to adopt in this setting.